CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a divisional of U.S. patent application Ser. No. 16/961,366, filed Jul. 10, 2020, which is a national stage filing under U.S.C. § 371 of PCT International Application PCT/US2019/013481, filed Jan. 14, 2019, which claims the benefit of U.S. Provisional Application No. 62/616,665, filed Jan. 12, 2018, the entirety of each of which is hereby incorporated by reference.
TECHNICAL FIELD OF THE INVENTION
The present invention relates to compounds and methods useful for the modulation of targeted ubiquitination, especially with respect to a variety of polypeptides and other proteins, which are degraded and/or otherwise inhibited by compounds according to the present invention. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.
BACKGROUND OF THE INVENTION
Ubiquitin-Proteasome Pathway (UPP) is a critical pathway that regulates key regulator proteins and degrades misfolded or abnormal proteins. UPP is central to multiple cellular processes, and if defective or imbalanced, it leads to pathogenesis of a variety of diseases. The covalent attachment of ubiquitin to specific protein substrates is achieved through the action of E3 ubiquitin ligases. These ligases comprise over 500 different proteins and are categorized into multiple classes defined by the structural element of their E3 functional activity.
Cereblon (CRBN) interacts with damaged DNA binding protein 1 and forms an E3 ubiquitin ligase complex with Cullin 4 where it functions as a substrate receptor in which the proteins recognized by CRBN might be ubiquitinated and degraded by proteasomes.
Proteasome-mediated degradation of unneeded or damaged proteins plays a very important role in maintaining regular function of a cell, such as cell survival, proliferation and growth. A new role for CRBN has been identified; i.e., the binding of immunomodulatory drugs (IMiDs), e.g. thalidomide, to CRBN has now been associated with teratogenicity and also the cytotoxicity of IMiDs, including lenalidomide, which are widely used to treat multiple myeloma patients. CRBN is likely a key player in the binding, ubiquitination and degradation of factors involved in maintaining function of myeloma cells. These new findings regarding the role of CRBN in IMiD action stimulated intense investigation of CRBN's downstream factors involved in maintaining regular function of a cell (Chang and Stewart Int J Biochem Mol Biol. 2011; 2(3): 287-294).
UPP plays a key role in the degradation of short-lived and regulatory proteins important in a variety of basic cellular processes, including regulation of the cell cycle, modulation of cell surface receptors and ion channels, and antigen presentation. The pathway has been implicated in several forms of malignancy, in the pathogenesis of several genetic diseases (including cystic fibrosis, Angelman's syndrome, and Liddle syndrome), in immune surveillance/viral pathogenesis, and in the pathology of muscle wasting. Many diseases are associated with an abnormal UPP and negatively affect cell cycle and division, the cellular response to stress and to extracellular modulators, morphogenesis of neuronal networks, modulation of cell surface receptors, ion channels, the secretory pathway, DNA repair and biogenesis of organelles.
Aberrations in the process have recently been implicated in the pathogenesis of several diseases, both inherited and acquired. These diseases fall into two major groups: (a) those that result from loss of function with the resultant stabilization of certain proteins, and (b) those that result from gain of function, i.e. abnormal or accelerated degradation of the protein target.
The UPP is used to induce selective protein degradation, including use of fusion proteins to artificially ubiquitinate target proteins and synthetic small-molecule probes to induce proteasome-dependent degradation. Bifunctional compounds composed of a target protein-binding ligand and an E3 ubiquitin ligase ligand, induced proteasome-mediated degradation of selected proteins via their recruitment to E3 ubiquitin ligase and subsequent ubiquitination. These drug-like molecules offer the possibility of temporal control over protein expression. Such compounds are capable of inducing the inactivation of a protein of interest upon addition to cells or administration to an animal or human, and could be useful as biochemical reagents and lead to a new paradigm for the treatment of diseases by removing pathogenic or oncogenic proteins (Crews C, Chemistry & Biology, 2010, 17(6):551-555; Schnnekloth J S Jr., Chembiochem, 2005, 6(1):40-46).
An ongoing need exists in the art for effective treatments for disease, especially hyperplasias and cancers, such as multiple myeloma. However, non-specific effects, and the inability to target and modulate certain classes of proteins altogether, such as transcription factors, remain as obstacles to the development of effective anti-cancer agents. As such, small molecule therapeutic agents that leverage or potentiate cereblon's substrate specificity and, at the same time, are“tunable” such that a wide range of protein classes can be targeted and modulated with specificity would be very useful as a therapeutic. Accordingly, there remains a need to find bifunctional compounds that are protein degraders useful as therapeutic agents.
SUMMARY OF THE INVENTION
The present application relates novel bifunctional compounds, which function to recruit targeted proteins to E3 Ubiquitin Ligase for degradation, and methods of preparation and uses thereof. In particular, the present disclosure provides bifunctional compounds, which find utility as modulators of targeted ubiquitination of a variety of polypeptides and other proteins, which are then degraded and/or otherwise inhibited by the bifunctional compounds as described herein. An advantage of the compounds provided herein is that a broad range of pharmacological activities is possible, consistent with the degradation/inhibition of targeted polypeptides from virtually any protein class or family. In addition, the description provides methods of using an effective amount of the compounds as described herein for the treatment or amelioration of a disease condition, such as cancer, e.g., multiple myeloma.
The present application further relates to targeted degradation of proteins through the use of bifunctional molecules, including bifunctional molecules that link a cereblon-binding moiety to a ligand that binds the targeted protein.
The present application also relates to a bifunctional compound having the following structure:
wherein,
TBM is a target binding moiety capable of binding to the targeted protein(s);
L is a bivalent moiety that connects TBM to UBM; and
UBM is a ubiquitin binding moiety capable of binding to a ubiquitin ligase such as an E3 Ubiquitin Ligase (e.g., cereblon).
It has now been found that compounds of this invention, and pharmaceutically acceptable compositions thereof, are effective for the modulation of targeted ubiquitination. Such compounds have the general Formula I:
or a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described herein.
It has also now been found that other compounds of this invention, and pharmaceutically acceptable compositions thereof, are effective for the modulation of targeted ubiquitination. Such compounds have the general Formula I′:
or a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described herein.
Compounds of the present invention, and pharmaceutically acceptable compositions thereof, are useful for treating a variety of diseases, disorders or conditions. Such diseases, disorders, or conditions include those described herein.
Compounds provided by this invention are also useful for the study of CRBN and targeted proteins in biological and pathological phenomena; the study of CRBN and targeted proteins occurring in bodily tissues; and the comparative evaluation of new CRBN or targeted protein ligands or other regulators of CRBN or targeted proteins in vitro or in vivo.
DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS 1. General Description of Certain Embodiments of the Invention
Compounds of the present invention, and compositions thereof, are useful for the modulation of targeted ubiquitination.
As defined herein, the terms “binder,” “modulator,” and “ligand” are used interchangeably and describe a compound that binds to, modulates or is a ligand for CRBN or a targeted protein.
In certain embodiments, the present invention provides a compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
Ring A is selected from
- each of X1 and X6 is independently a bivalent moiety selected from a covalent bond, —O—, —CH2—, —C(R1)H—, —C(R1)2—, —C(O)—, —C(NR1)—, —C(S)—, or
- X2 is a trivalent moiety selected from
- each of X3 and X4 is independently a bivalent moiety selected from a covalent bond, —O—, —S—, —S(O)—, —S(O)2—, or —N(R)—;
- X5 is a bivalent moiety selected from a covalent bond, —O—, —CH2—, —C(R1)H—, —C(R1)2—, —C(NR1)—, —C(S)—, or
- each R is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or
- two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, or sulfur;
- each R1 is independently hydrogen, deuterium, halogen, —CN, —OR, —SR, —S(O)R, —S(O)2R, —N(R)2, or an optionally substituted C1-4 aliphatic; or
- two R1 groups on the same carbon are optionally taken together with their intervening atoms to form a 3-6 membered spiro fused ring; or
- two R1 groups on adjacent carbon atoms are optionally taken together with their intervening atoms to form a 3-6 membered saturated, partially unsaturated, or aryl fused ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- each R2 is independently hydrogen, halogen, —CN, —NO2, —OR, —SR, —N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, —N(R)S(O)2R, optionally substituted C1-6 aliphatic, optionally substituted phenyl, an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- L1 is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-6 hydrocarbon chain, wherein 1-2 methylene units of L1 are independently and optionally replaced by —O—, —NR3—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —S(O)—, —S(O)2—, —NR3S(O)2—, —S(O)2NR3—, —NR3C(O)—, —C(O)NR3—, —OC(O)NR3—, —NR3C(O)O—,
provided that L1 is not a covalent bond, —CH2—, —C(O)O—, —C(O)OCH2—, —CH2C(O)—, —C(O)CH2—, —NR3C(O)—, —C(O)NR3—, or —CH2CH2— when Ring A is
and X1 is —C(O)— or Ring A is
and
L2 is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-50 hydrocarbon chain, wherein 0-6 methylene units of L2 are independently replaced by -Cy-, —O—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —S(O)—, —S(O)2—, —NRS(O)2—, —S(O)2NR—, —NRC(O)—, —C(O)NR—, —OC(O)NR—, —NRC(O)O—,
wherein:
- each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, 8-10 membered bicyclic arylenyl, 4-7 membered saturated or partially unsaturated carbocyclylenyl, 4-7 membered saturated or partially unsaturated spiro carbocyclylenyl, 8-10 membered bicyclic saturated or partially unsaturated carbocyclylenyl, 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- each R3 is independently hydrogen or C1-4 aliphatic;
- Ring B is a bivalent ring selected from 4-7 membered saturated or partially unsaturated carbocyclylenyl, phenylenyl, 8-10 membered bicyclic arylenyl, 5-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 8-10 membered partially saturated bicyclic heteroarylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 8-10 membered bicyclic heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein Ring B is optionally further substituted with 1-2 oxo groups;
- TBM is a target binding moiety;
- m is 0, 1, 2, 3, or 4;
- n is 0, 1, 2, 3, or 4; and
- each of p is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
In another aspect, the present invention provides a compound of Formula I′:
or a pharmaceutically acceptable salt thereof, wherein:
- each of X1, X5, and X6 is independently a bivalent moiety selected from a covalent bond, —O—, —S—, —C(R1)CF3—, —C(R1)2—, —C(O)—, —N(R1)—, —C(NR1)—, —C(S)—, —Si(R1)2—, —P(O)(R1)—, —P(O)(OR1)—, —P(O)N(R1)2—, or
- X2 is a trivalent moiety selected from
- each of X3 and X4 is independently a bivalent moiety selected from a covalent bond, —O—, —S—, —C(R1)F—, —CF2—, —C(R1)2—, —S(O)—, —S(O)2—, —Si(R1)2—, —P(O)(R1)—, or —N(R)—;
- each R is independently hydrogen, deuterium, or an optionally substituted group selected from C1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur, and a 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur; or
- two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-8 membered saturated, partially unsaturated, or heteroaryl monocyclic ring having 0-1 heteroatom, in addition to the nitrogen, independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 0-2 heteroatoms, in addition to the nitrogen, independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- each R1 is independently hydrogen, deuterium, halogen, —CN, —OR, —SR, —S(O)R, —S(O)2R, —N(R)2, —P(O)(OR)2, —P(O)(NR2)OR, —P(O)(NR2)2, —Si(OH)R2, —Si(OH)2R, —SiR3, or an optionally substituted C1-4 aliphatic; or
- R1 and X1 or X4 are taken together with their intervening atoms to form a 5-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- two R1 groups on the same carbon are optionally taken together with their intervening atoms to form a 3-6 membered spiro fused ring or a 4-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- two R1 groups on adjacent carbon atoms are optionally taken together with their intervening atoms to form a 3-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- each R2 is independently hydrogen, deuterium, halogen, —CN, —NO2, —OR, —SR, —NR2, —Si(OH)2R, —Si(OH)(R)2, —Si(R)3, —S(O)2R, —S(O)2NR2, —S(O)R, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, —N(R)S(O)2R, —N(R)S(O)2NR2, —P(O)(OR)2, —P(O)(NR2)OR, —P(O)(NR2)2, optionally substituted C1-6 aliphatic, optionally substituted phenyl, optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, optionally substituted 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur; or a 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- L1 is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-6 hydrocarbon chain, wherein 1-2 methylene units of L1 are independently and optionally replaced by —O—, —NR3—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —Si(R1)2—, —P(O)(R1)—, —P(O)(OR)—, —P(O)(NR2)—, —S(O)—, —S(O)2—, —NR3S(O)2—, —S(O)2NR3—, —NR3C(O)—, —C(O)NR3—, —OC(O)NR3—, —NR3C(O)O—,
provided that L1 is other than a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-6 hydrocarbon chain, wherein 1-2 methylene units of L1 are independently and optionally replaced by —O—, —NR3—, —OC(O)—, —C(O)O—, —C(O)—, —NR3S(O)2—, —S(O)2NR3—, —N(R)C(O)—, —C(O)N(R)—, or —NR3C(O)O— when Ring A is
and X1 is —C(O)—, Ring A is
and X2 is
or
Ring A is
and X2 is
Ring A is
Ring A is
and X1 is —C(O)— or —CH2—, or Ring A is
and X2 is
or
each R3 is independently hydrogen, deuterium, or optionally substituted C1-4 aliphatic;
L2 is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-50 hydrocarbon chain, wherein 0-6 methylene units of L2 are independently replaced by -Cy-, —O—, —NR—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —S(O)—, —S(O)2—, —NRS(O)2—, —S(O)2NR—, —NRC(O)—, —C(O)NR—, —OC(O)NR—, —NRC(O)O—,
wherein:
- each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, 8-10 membered bicyclic arylenyl, 4-7 membered saturated or partially unsaturated carbocyclylenyl, 4-7 membered saturated or partially unsaturated spiro carbocyclylenyl, 8-10 membered bicyclic saturated or partially unsaturated carbocyclylenyl, 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- Ring B is selected from a 3 to 7-membered saturated or partially unsaturated carbocyclic ring, phenyl, 8-10 membered bicyclic carbocyclic aromatic ring, 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur; wherein Ring B is optionally further substituted with 1-2 oxo groups;
- TBM is a target binding moiety;
- m is 0, 1, 2, 3, or 4;
- n is 0, 1, 2, 3, or 4; and
- each of p is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
2. Compounds and Definitions
Compounds of the present invention include those described generally herein, and are further illustrated by the classes, subclasses, and species disclosed herein. As used herein, the following definitions shall apply unless otherwise indicated. For purposes of this invention, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th Ed. Additionally, general principles of organic chemistry are described in “Organic Chemistry”, Thomas Sorrell, University Science Books, Sausalito: 1999, and “March's Advanced Organic Chemistry”, 5th Ed., Ed.: Smith, M. B. and March, J., John Wiley & Sons, New York: 2001, the entire contents of which are hereby incorporated by reference.
The term “aliphatic” or “aliphatic group”, as used herein, means a straight-chain (i.e., unbranched) or branched, substituted or unsubstituted hydrocarbon chain that is completely saturated or that contains one or more units of unsaturation, or a monocyclic hydrocarbon or bicyclic hydrocarbon that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic (also referred to herein as “carbocycle,” “cycloaliphatic” or “cycloalkyl”), that has a single point of attachment to the rest of the molecule. Unless otherwise specified, aliphatic groups contain 1-6 aliphatic carbon atoms. In some embodiments, aliphatic groups contain 1-5 aliphatic carbon atoms. In other embodiments, aliphatic groups contain 1-4 aliphatic carbon atoms. In still other embodiments, aliphatic groups contain 1-3 aliphatic carbon atoms, and in yet other embodiments, aliphatic groups contain 1-2 aliphatic carbon atoms. In some embodiments, “cycloaliphatic” (or “carbocycle” or “cycloalkyl”) refers to a monocyclic C3-C6 hydrocarbon that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic, that has a single point of attachment to the rest of the molecule. Suitable aliphatic groups include, but are not limited to, linear or branched, substituted or unsubstituted alkyl, alkenyl, alkynyl groups and hybrids thereof such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl.
As used herein, the term “bridged bicyclic” refers to any bicyclic ring system, i.e. carbocyclic or heterocyclic, saturated or partially unsaturated, having at least one bridge. As defined by IUPAC, a “bridge” is an unbranched chain of atoms or an atom or a valence bond connecting two bridgeheads, where a “bridgehead” is any skeletal atom of the ring system which is bonded to three or more skeletal atoms (excluding hydrogen). In some embodiments, a bridged bicyclic group has 7-12 ring members and 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Such bridged bicyclic groups are well known in the art and include those groups set forth below where each group is attached to the rest of the molecule at any substitutable carbon or nitrogen atom. Unless otherwise specified, a bridged bicyclic group is optionally substituted with one or more substituents as set forth for aliphatic groups. Additionally or alternatively, any substitutable nitrogen of a bridged bicyclic group is optionally substituted. Exemplary bridged bicyclics include:
The term “lower alkyl” refers to a C1-4 straight or branched alkyl group. Exemplary lower alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tert-butyl.
The term “lower haloalkyl” refers to a C1-4 straight or branched alkyl group that is substituted with one or more halogen atoms.
The term “heteroatom” means one or more of oxygen, sulfur, nitrogen, phosphorus, or silicon (including, any oxidized form of nitrogen, sulfur, phosphorus, or silicon; the quaternized form of any basic nitrogen or; a substitutable nitrogen of a heterocyclic ring, for example N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl) or NR+ (as in N-substituted pyrrolidinyl)).
The term “unsaturated,” as used herein, means that a moiety has one or more units of unsaturation.
As used herein, the term “bivalent C1-8 (or C1-6) saturated or unsaturated, straight or branched, hydrocarbon chain”, refers to bivalent alkylene, alkenylene, and alkynylene chains that are straight or branched as defined herein.
The term “alkylene” refers to a bivalent alkyl group. An “alkylene chain” is a polymethylene group, i.e., —(CH2)n—, wherein n is a positive integer, preferably from 1 to 6, from 1 to 4, from 1 to 3, from 1 to 2, or from 2 to 3. A substituted alkylene chain is a polymethylene group in which one or more methylene hydrogen atoms are replaced with a substituent. Suitable substituents include those described below for a substituted aliphatic group.
The term “alkenylene” refers to a bivalent alkenyl group. A substituted alkenylene chain is a polymethylene group containing at least one double bond in which one or more hydrogen atoms are replaced with a substituent. Suitable substituents include those described below for a substituted aliphatic group.
As used herein, the term “cyclopropylenyl” refers to a bivalent cyclopropyl group of the following structure:
The term “halogen” means F, Cl, Br, or I.
The term “aryl” used alone or as part of a larger moiety as in “aralkyl,” “aralkoxy,” or “aryloxyalkyl,” refers to monocyclic or bicyclic ring systems having a total of five to fourteen ring members, wherein at least one ring in the system is aromatic and wherein each ring in the system contains 3 to 7 ring members. The term “aryl” may be used interchangeably with the term “aryl ring.” In certain embodiments of the present invention, “aryl” refers to an aromatic ring system which includes, but not limited to, phenyl, biphenyl, naphthyl, anthracyl and the like, which may bear one or more substituents. Also included within the scope of the term “aryl,” as it is used herein, is a group in which an aromatic ring is fused to one or more non-aromatic rings, such as indanyl, phthalimidyl, naphthimidyl, phenanthridinyl, or tetrahydronaphthyl, and the like.
The terms “heteroaryl” and “heteroar-,” used alone or as part of a larger moiety, e.g., “heteroaralkyl,” or “heteroaralkoxy,” refer to groups having 5 to 10 ring atoms, preferably 5, 6, or 9 ring atoms; having 6, 10, or 14 π electrons shared in a cyclic array; and having, in addition to carbon atoms, from one to five heteroatoms. The term “heteroatom” refers to nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur, and any quaternized form of a basic nitrogen. Heteroaryl groups include, without limitation, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl, and pteridinyl. The terms “heteroaryl” and “heteroar-”, as used herein, also include groups in which a heteroaromatic ring is fused to one or more aryl, cycloaliphatic, or heterocyclyl rings, where the radical or point of attachment is on the heteroaromatic ring. Nonlimiting examples include indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H-quinolizinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and pyrido[2,3-b]-1,4-oxazin-3(4H)-one. A heteroaryl group may be mono- or bicyclic. The term “heteroaryl” may be used interchangeably with the terms “heteroaryl ring,” “heteroaryl group,” or “heteroaromatic,” any of which terms include rings that are optionally substituted. The term “heteroaralkyl” refers to an alkyl group substituted by a heteroaryl, wherein the alkyl and heteroaryl portions independently are optionally substituted.
As used herein, the terms “heterocycle,” “heterocyclyl,” “heterocyclic radical,” and “heterocyclic ring” are used interchangeably and refer to a stable 5- to 7-membered monocyclic or 7-10-membered bicyclic heterocyclic moiety that is either saturated or partially unsaturated, and having, in addition to carbon atoms, one or more, preferably one to four, heteroatoms, as defined above. When used in reference to a ring atom of a heterocycle, the term “nitrogen” includes a substituted nitrogen. As an example, in a saturated or partially unsaturated ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, the nitrogen may be N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl), or +NR (as in N-substituted pyrrolidinyl).
A heterocyclic ring can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure and any of the ring atoms can be optionally substituted. Examples of such saturated or partially unsaturated heterocyclic radicals include, without limitation, tetrahydrofuranyl, tetrahydrothiophenyl pyrrolidinyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, 2-oxa-6-azaspiro[3.3]heptane, and quinuclidinyl. The terms “heterocycle,” “heterocyclyl,” “heterocyclyl ring,” “heterocyclic group,” “heterocyclic moiety,” and “heterocyclic radical,” are used interchangeably herein, and also include groups in which a heterocyclyl ring is fused to one or more aryl, heteroaryl, or cycloaliphatic rings, such as indolinyl, 3H-indolyl, chromanyl, phenanthridinyl, or tetrahydroquinolinyl. A heterocyclyl group may be mono- or bicyclic. The term “heterocyclylalkyl” refers to an alkyl group substituted by a heterocyclyl, wherein the alkyl and heterocyclyl portions independently are optionally substituted.
As used herein, the term “partially unsaturated” refers to a ring moiety that includes at least one double or triple bond. The term “partially unsaturated” is intended to encompass rings having multiple sites of unsaturation, but is not intended to include aryl or heteroaryl moieties, as herein defined.
As described herein, compounds of the invention may contain “optionally substituted” moieties. In general, the term “substituted,” whether preceded by the term “optionally” or not, means that one or more hydrogens of the designated moiety are replaced with a suitable substituent. Unless otherwise indicated, an “optionally substituted” group may have a suitable substituent at each substitutable position of the group, and when more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at every position. Combinations of substituents envisioned by this invention are preferably those that result in the formation of stable or chemically feasible compounds. The term “stable,” as used herein, refers to compounds that are not substantially altered when subjected to conditions to allow for their production, detection, and, in certain embodiments, their recovery, purification, and use for one or more of the purposes disclosed herein.
Suitable monovalent substituents on a substitutable carbon atom of an “optionally substituted” group are independently halogen; —(CH2)0-4R∘; —(CH2)0-4OR∘; —O(CH2)0-4R∘, —O—(CH2)0-4C(O)OR∘; —(CH2)0-4CH(OR∘)2; —(CH2)0-4SR∘; —(CH2)0-4Ph, which may be substituted with R∘; —(CH2)0-4O(CH2)0-1Ph which may be substituted with R∘; —CH═CHPh, which may be substituted with R∘; —(CH2)0-4O(CH2)0-1-pyridyl which may be substituted with R∘; —NO2; —CN; —N3; —(CH2)0-4N(R∘)2; —(CH2)0-4N(R∘)C(O)R∘; —N(R∘)C(S)R∘; —(CH2)0-4N(R∘)C(O)NR∘2; —N(R∘)C(S)NR∘2; —(CH2)0-4N(R∘)C(O)OR∘; —N(R∘)N(R∘)C(O)R∘; —N(R∘)N(R∘)C(O)NR∘2; —N(R∘)N(R∘)C(O)OR∘; —(CH2)0-4C(O)R∘; —C(S)R∘; —(CH2)0-4C(O)OR∘; —(CH2)0-4C(O)SR∘; —(CH2)0-4C(O)OSiR∘3; —(CH2)0-4OC(O)R∘; —OC(O)(CH2)0-4SR∘; —SC(S)SR∘; —(CH2)0-4SC(O)R∘; —(CH2)0-4C(O)NR∘)2; —C(S)NR∘)2; —C(S)SR∘; —(CH2)0-4OC(O)NR∘2; —C(O)N(OR∘)R∘; —C(O)C(O)R∘; —C(O)CH2C(O)R∘; —C(NOR∘)R∘; —(CH2)0-4SSR∘; —(CH2)0-4S(O)2R∘; —(CH2)0-4S(O)2OR∘; —(CH2)0-4OS(O)2R∘; —S(O)2NR∘2; —(CH2)0-4S(O)R∘; —N(R∘)S(O)2NR∘2; —N(R∘)S(O)2R∘; —N(OR∘)R∘; —C(NH)NR∘)2; —P(O)2R∘; —P(O)R∘)2; —OP(O)R∘2; —OP(O)(OR∘)2; —SiR∘3; —(C1-4 straight or branched)alkylene)O—N(R∘)2; or —(C1-4 straight or branched)alkylene)C(O)O—N(R∘)2, wherein each R∘ may be substituted as defined below and is independently hydrogen, C1-6 aliphatic, —CH2Ph, −O(CH2)0-1Ph, —CH2-(5-6 membered heteroaryl ring), or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R∘, taken together with their intervening atom(s), form a 3-12-membered saturated, partially unsaturated, or aryl mono- or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which may be substituted as defined below.
Suitable monovalent substituents on R∘ (or the ring formed by taking two independent occurrences of R∘ together with their intervening atoms), are independently halogen, —(CH2)0-2R●, -(haloR●), —(CH2)0-2OH, —(CH2)0-2OR●, —(CH2)0-2CH(OR●)2; —O(haloR●), —CN, —N3, —(CH2)0-2C(O)R●, —(CH2)0-2C(O)OH, —(CH2)0-2C(O)OR●, —(CH2)0-2SR●, —(CH2)0-2SH, —(CH2)0-2NH2, —(CH2)0-2 NHR●, —(CH2)0-2NR●2, —NO2, —SiR●3, —OSiR●3, —C(O)SR●, —(C1-4 straight or branched alkylene)C(O)OR●, or —SSR● wherein each R● is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently selected from C1-4 aliphatic, —CH2Ph, —O(CH2)0-1Ph, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents on a saturated carbon atom of R∘ include ═O and ═S.
Suitable divalent substituents on a saturated carbon atom of an “optionally substituted” group include the following: ═O, ═S, ═NNR*2, ═NNHC(O)R*, ═NNHC(O)OR*, ═NNHS(O)2R*, ═NR*, ═NOR*, —O(C(R*2))2-3O—, or —S(C(R*2))2-3S—, wherein each independent occurrence of R* is selected from hydrogen, C1-6 aliphatic which may be substituted as defined below, or an unsubstituted 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents that are bound to vicinal substitutable carbons of an “optionally substituted” group include: —O(CR*2)2-3O—, wherein each independent occurrence of R* is selected from hydrogen, C1-6 aliphatic which may be substituted as defined below, or an unsubstituted 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
Suitable substituents on the aliphatic group of R* include halogen, —R●, -(haloR●), —OH, −OR●, —O(haloR●), —CN, —C(O)OH, —C(O)OR●, —NH2, —NHR●, —NR●2, or —NO2, wherein each R● is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently C1-4 aliphatic, —CH2Ph, —O(CH2)0-1Ph, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
Suitable substituents on a substitutable nitrogen of an “optionally substituted” group include —R†, —NR†2, —C(O)R†, —C(O)OR†, —C(O)C(O)R†, —C(O)CH2C(O)R†, —S(O)2R†, —S(O)2NR†2, —C(S)NR†2, —C(NH)NR†2, or —N(R†)S(O)2R†; wherein each R† is independently hydrogen, C1-6 aliphatic which may be substituted as defined below, unsubstituted —OPh, or an unsubstituted 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R†, taken together with their intervening atom(s) form an unsubstituted 3-12-membered saturated, partially unsaturated, or aryl mono- or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
Suitable substituents on the aliphatic group of R† are independently halogen, —R●, -(haloR●), —OH, −OR●, —O(haloR●), —CN, —C(O)OH, —C(O)OR●, —NH2, —NHR●, —NR●2, or —NO2, wherein each R● is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently C1-4 aliphatic, —CH2Ph, —O(CH2)0-1Ph, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
As used herein, the term “pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S. M. Berge et al., describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19, incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of this invention include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like.
Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N+(C1-4alkyl)4 salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, loweralkyl sulfonate and aryl sulfonate.
Unless otherwise stated, structures depicted herein are also meant to include all isomeric (e.g., enantiomeric, diastereomeric, and geometric (or conformational)) forms of the structure; for example, the R and S configurations for each asymmetric center, Z and E double bond isomers, and Z and E conformational isomers. Therefore, single stereochemical isomers as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures of the present compounds are within the scope of the invention. Unless otherwise stated, all tautomeric forms of the compounds of the invention are within the scope of the invention. Additionally, unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures including the replacement of hydrogen by deuterium or tritium, or the replacement of a carbon by a 13C- or 14C-enriched carbon are within the scope of this invention. Such compounds are useful, for example, as analytical tools, as probes in biological assays, or as therapeutic agents in accordance with the present invention. In certain embodiments, a provided compound may be substituted with one or more deuterium atoms.
As used herein, the term “provided compound” refers to any genus, subgenus, and/or species set forth herein.
As used herein, the term “binder” or “inhibitor” is defined as a compound that binds to CRBN and binds to or inhibits a targeted protein with measurable affinity. In certain embodiments, an inhibitor has an IC50 and/or binding constant of less than about 50 μM, less than about 1 μM, less than about 500 nM, less than about 100 nM, less than about 10 nM, or less than about 1 nM.
A compound of the present invention may be tethered to a detectable moiety. It will be appreciated that such compounds are useful as imaging agents. One of ordinary skill in the art will recognize that a detectable moiety may be attached to a provided compound via a suitable substituent. As used herein, the term “suitable substituent” refers to a moiety that is capable of covalent attachment to a detectable moiety. Such moieties are well known to one of ordinary skill in the art and include groups containing, e.g., a carboxylate moiety, an amino moiety, a thiol moiety, or a hydroxyl moiety, to name but a few. It will be appreciated that such moieties may be directly attached to a provided compound or via a tethering group, such as a bivalent saturated or unsaturated hydrocarbon chain. In some embodiments, such moieties may be attached via click chemistry. In some embodiments, such moieties may be attached via a 1,3-cycloaddition of an azide with an alkyne, optionally in the presence of a copper catalyst. Methods of using click chemistry are known in the art and include those described by Rostovtsev et al., Angew. Chem. Int. Ed. 2002, 41, 2596-99 and Sun et al., Bioconjugate Chem., 2006, 17, 52-57.
As used herein, the term “detectable moiety” is used interchangeably with the term “label” and relates to any moiety capable of being detected, e.g., primary labels and secondary labels. Primary labels, such as radioisotopes (e.g., tritium, 32P, 33P, 35S, or 14C), mass-tags, and fluorescent labels are signal generating reporter groups which can be detected without further modifications. Detectable moieties also include luminescent and phosphorescent groups.
The term “secondary label” as used herein refers to moieties such as biotin and various protein antigens that require the presence of a second intermediate for production of a detectable signal. For biotin, the secondary intermediate may include streptavidin-enzyme conjugates. For antigen labels, secondary intermediates may include antibody-enzyme conjugates. Some fluorescent groups act as secondary labels because they transfer energy to another group in the process of nonradiative fluorescent resonance energy transfer (FRET), and the second group produces the detected signal.
The terms “fluorescent label”, “fluorescent dye”, and “fluorophore” as used herein refer to moieties that absorb light energy at a defined excitation wavelength and emit light energy at a different wavelength. Examples of fluorescent labels include, but are not limited to: Alexa Fluor dyes (Alexa Fluor 350, Alexa Fluor 488, Alexa Fluor 532, Alexa Fluor 546, Alexa Fluor 568, Alexa Fluor 594, Alexa Fluor 633, Alexa Fluor 660 and Alexa Fluor 680), AMCA, AMCA-S, BODIPY dyes (BODIPY FL, BODIPY R6G, BODIPY TMR, BODIPY TR, BODIPY 530/550, BODIPY 558/568, BODIPY 564/570, BODIPY 576/589, BODIPY 581/591, BODIPY 630/650, BODIPY 650/665), Carboxyrhodamine 6G, carboxy-X-rhodamine (ROX), Cascade Blue, Cascade Yellow, Coumarin 343, Cyanine dyes (Cy3, Cy5, Cy3.5, Cy5.5), Dansyl, Dapoxyl, Dialkylaminocoumarin, 4′,5′-Dichloro-2′,7′-dimethoxy-fluorescein, DM-NERF, Eosin, Erythrosin, Fluorescein, FAM, Hydroxycoumarin, IRDyes (IRD40, IRD 700, IRD 800), JOE, Lissamine rhodamine B, Marina Blue, Methoxycoumarin, Naphthofluorescein, Oregon Green 488, Oregon Green 500, Oregon Green 514, Pacific Blue, PyMPO, Pyrene, Rhodamine B, Rhodamine 6G, Rhodamine Green, Rhodamine Red, Rhodol Green, 2′,4′,5′,7′-Tetra-bromosulfone-fluorescein, Tetramethyl-rhodamine (TMR), Carboxytetramethylrhodamine (TAMRA), Texas Red, Texas Red-X.
The term “mass-tag” as used herein refers to any moiety that is capable of being uniquely detected by virtue of its mass using mass spectrometry (MS) detection techniques. Examples of mass-tags include electrophore release tags such as N-[3-[4′-[(p-Methoxytetrafluorobenzyl)oxy]phenyl]-3-methylglyceronyl]isonipecotic Acid, 4′-[2,3,5,6-Tetrafluoro-4-(pentafluorophenoxyl)]methyl acetophenone, and their derivatives. The synthesis and utility of these mass-tags is described in U.S. Pat. Nos. 4,650,750, 4,709,016, 5,360,8191, 5,516,931, 5,602,273, 5,604,104, 5,610,020, and 5,650,270. Other examples of mass-tags include, but are not limited to, nucleotides, dideoxynucleotides, oligonucleotides of varying length and base composition, oligopeptides, oligosaccharides, and other synthetic polymers of varying length and monomer composition. A large variety of organic molecules, both neutral and charged (biomolecules or synthetic compounds) of an appropriate mass range (100-2000 Daltons) may also be used as mass-tags.
The terms “measurable affinity” and “measurably modulate,” as used herein, means a measurable change in a CRBN activity between a sample comprising a compound of the present invention, or composition thereof, and CRBN, and an equivalent sample comprising CRBN, in the absence of said compound, or composition thereof.
3. Description of Exemplary Embodiments
As described above, in certain embodiments, the present invention provides a compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
- each of X1 and X6 is independently a bivalent moiety selected from a covalent bond, —O—, —CH2—, —C(R1)H—, —C(R1)2—, —C(O)—, —C(NR1)—, —C(S)—, or
- X2 is a trivalent moiety selected from
- each of X3 and X4 is independently a bivalent moiety selected from a covalent bond, —O—, —S—, —S(O)—, —S(O)2—, or —N(R)—;
- X5 is a bivalent moiety selected from a covalent bond, —O—, —CH2—, —C(R1)H—, —C(R1)2—, —C(NR1)—, —C(S)—, or
- each R is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or
- two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, or sulfur;
- each R1 is independently hydrogen, deuterium, halogen, —CN, —OR, —SR, —S(O)R, —S(O)2R, —N(R)2, or an optionally substituted C1-4 aliphatic; or
- two R1 groups on the same carbon are optionally taken together with their intervening atoms to form a 3-6 membered spiro fused ring; or
- two R1 groups on adjacent carbon atoms are optionally taken together with their intervening atoms to form a 3-6 membered saturated, partially unsaturated, or aryl fused ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- each R2 is independently hydrogen, halogen, —CN, —NO2, —OR, —SR, —N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, —N(R)S(O)2R, optionally substituted C1-6 aliphatic, optionally substituted phenyl, an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- L1 is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-6 hydrocarbon chain, wherein 1-2 methylene units of L are independently and optionally replaced by —O—, —NR3—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —S(O)—, —S(O)2—, —NR3S(O)2—, —S(O)2NR3—, —NR3C(O)—, —C(O)NR3—, —OC(O)NR3—, —NR3C(O)O—,
provided that L is not a covalent bond, —CH2—, —C(O)O—, —C(O)OCH2—, —CH2C(O)—, —C(O)CH2—, —NR3C(O)—, —C(O)NR3—, or —CH2CH2— when Ring A is
and X1 is —C(O)— or Ring A is
and X2 is
- L2 is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, —O—, —NR—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —S(O)—, —S(O)2—, —NRS(O)2—, —S(O)2NR—, —NRC(O)—, —C(O)NR—, —OC(O)NR—, —NRC(O)O—,
wherein:
- each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, 8-10 membered bicyclic arylenyl, 4-7 membered saturated or partially unsaturated carbocyclylenyl, 4-7 membered saturated or partially unsaturated spiro carbocyclylenyl, 8-10 membered bicyclic saturated or partially unsaturated carbocyclylenyl, 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- each R3 is independently hydrogen or C1-4 aliphatic;
- Ring B is a bivalent ring selected from 4-7 membered saturated or partially unsaturated carbocyclylenyl, phenylenyl, 8-10 membered bicyclic arylenyl, 5-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 8-10 membered partially saturated bicyclic heteroarylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 8-10 membered bicyclic heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein Ring B is optionally further substituted with 1-2 oxo groups;
- TBM is a target binding moiety;
- m is 0, 1, 2, 3, or 4;
- n is 0, 1, 2, 3, or 4; and
each of p is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
As described above, in another aspect, the present invention provides a compound of Formula I′:
or a pharmaceutically acceptable salt thereof, wherein:
- each of X1, X5, and X6 is independently a bivalent moiety selected from a covalent bond, —O—, —S—, —C(R1)CF3—, —C(R1)2—, —C(O)—, —N(R1)—, —C(NR1)—, —C(S)—, —Si(R1)2—, —P(O)(R1)—, —P(O)(OR1)—, —P(O)N(R1)2—, or
- X2 is a trivalent moiety selected from
- each of X3 and X4 is independently a bivalent moiety selected from a covalent bond, —O—, —S—, —C(R1)F—, —CF2—, —C(R1)2—, —S(O)—, —S(O)2—, —Si(R1)2—, —P(O)(R1)—, or —N(R)—;
- each R is independently hydrogen, deuterium, or an optionally substituted group selected from C1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur, and a 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur; or
- two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-8 membered saturated, partially unsaturated, or heteroaryl monocyclic ring having 0-1 heteroatoms, in addition to the nitrogen, independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 0-2 heteroatoms, in addition to the nitrogen, independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- each R1 is independently hydrogen, deuterium, halogen, —CN, —OR, —SR, —S(O)R, —S(O)2R, —N(R)2, —P(O)(OR)2, —P(O)(NR2)OR, —P(O)(NR2)2, —Si(OH)R2, —Si(OH)2R, —SiR3, or an optionally substituted C1-4 aliphatic; or
- R1 and X1 or X4 are taken together with their intervening atoms to form a 5-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- two R1 groups on the same carbon are optionally taken together with their intervening atoms to form a 3-6 membered spiro fused ring or a 4-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- two R1 groups on adjacent carbon atoms are optionally taken together with their intervening atoms to form a 3-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- each R2 is independently hydrogen, deuterium, halogen, —CN, —NO2, —OR, —SR, —NR2, —Si(OH)2R, —Si(OH)(R)2, —Si(R)3, —S(O)2R, —S(O)2NR2, —S(O)R, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, —N(R)S(O)2R, —N(R)S(O)2NR2, —P(O)(OR)2, —P(O)(NR2)OR, —P(O)(NR2)2, optionally substituted C1-6 aliphatic, optionally substituted phenyl, optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, optionally substituted 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur; or a 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- L1 is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-6 hydrocarbon chain, wherein 1-2 methylene units of L1 are independently and optionally replaced by —O—, —NR3—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —Si(R1)2—, —P(O)(R1)—, —P(O)(OR)—, —P(O)(NR2)—, —S(O)—, —S(O)2—, —NR3S(O)2—, —S(O)2NR3—, —NR3C(O)—, —C(O)NR3—, —OC(O)NR3—, —NR3C(O)O—,
provided that L1 is other than a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-6 hydrocarbon chain, wherein 1-2 methylene units of L1 are independently and optionally replaced by —O—, —NR3—, —OC(O)—, —C(O)O—, —C(O)—, —NR3S(O)2—, —S(O)2NR3—, —N(R)C(O)—, —C(O)N(R)—, or —NR3C(O)O— when Ring A is
and X1 is —C(O)—, Ring A is
and X2 is
or
Ring A is
and X2 is
Ring A is
Ring A is
and X1 is —C(O)— or —CH2—, or Ring A is
and X2 is
or
- each R3 is independently hydrogen, deuterium, or optionally substituted C1-4 aliphatic;
- L2 is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-50 hydrocarbon chain, wherein 0-6 methylene units of L2 are independently replaced by -Cy-, —O—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —S(O)—, —S(O)2—, —NRS(O)2—, —S(O)2NR—, —NRC(O)—, —C(O)NR—, —OC(O)NR—, —NRC(O)O—,
wherein:
- each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, 8-10 membered bicyclic arylenyl, 4-7 membered saturated or partially unsaturated carbocyclylenyl, 4-7 membered saturated or partially unsaturated spiro carbocyclylenyl, 8-membered bicyclic saturated or partially unsaturated carbocyclylenyl, 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- Ring B is selected from a 4 to 7-membered saturated or partially unsaturated carbocyclic ring, phenyl, an 8-10 membered bicyclic carbocyclic aromatic ring, a 5 to 7-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, a 5-6-membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or an 8-membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, wherein Ring B is optionally further substituted with 1-2 oxo groups;
- TBM is a target binding moiety;
- m is 0, 1, 2, 3, or 4;
- n is 0, 1, 2, 3, or 4; and
- each of p is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
As defined generally above, Ring A is selected from
In some embodiments, Ring A is selected from
In some embodiments, Ring A is selected from
In some embodiments, Ring A is selected from
In some embodiments, Ring A is selected from
In some embodiments, Ring A is selected from
In some embodiments, Ring A is selected from
In some embodiments, Ring A is selected from
In some embodiments, Ring A is selected from
In some embodiments, Ring A is selected from
In some embodiments, Ring A is selected from
In some embodiments, Ring A is selected from
In some embodiments, Ring A is selected from
In some embodiments, Ring A is selected from
In some embodiments, Ring A is selected from those depicted in Table 1, below.
As defined generally above, each of X1 and X6 is independently a bivalent moiety selected from a covalent bond, —O—, −S—, —CH2—, —C(R1)H—, —C(R1)CF3—, —C(R1)2—, —C(O)—, —C(NR1)—, —C(S)—, —N(R1)—, —Si(R1)2—, —P(O)(OR1)—, —P(O)(R1)—, —P(O)N(R1)2—, or
In some embodiments, X1 is a covalent bond. In some embodiments, X1 is —O—. In some embodiments, X1 is —S—. In some embodiments, X1 is —CH2—. In some embodiments, X1 is —C(R1)H—. In some embodiments, X1 is —C(R1)CF3—. In some embodiments, X1 is —C(O)—. In some embodiments, X1 is —C(NR1)—. In some embodiments, X1 is —C(S)—. In some embodiments, X1 is —N(R1)—. In some embodiments, X1 is —Si(R1)2—. In some embodiments, X1 is —P(O)(R1)—. In some embodiments, X1 is —P(O)(R1)—. In some embodiments, X1 is —P(O)N(R1)2—. In some embodiments, X1 is
In some embodiments, X6 is a covalent bond. In some embodiments, X6 is —O—. In some embodiments, X6 is —S—. In some embodiments, X6 is —CH2—. In some embodiments, X6 is —C(R1)H—. In some embodiments, X6 is —C(R1)CF3—. In some embodiments, X6 is —C(O)—. In some embodiments, X6 is —C(NR1)—. In some embodiments, X6 is —C(S)—. In some embodiments, X6 is —N(R1)—. In some embodiments, X6 is —Si(R1)2—. In some embodiments, X6 is —P(O)(R1)—. In some embodiments, X6 is —P(O)(R1)—. In some embodiments, X6 is —P(O)N(R1)2—. In some embodiments, X6 is
In some embodiments, X1 and X6 are each independently selected from —O—, —C(O)—, —C(S)—, —Si(R1)2—, —P(O)(R1)—, or
In some embodiments, X1 and X6 are each independently selected from those depicted in Table 1, below.
As defined generally above, X2 is a trivalent moiety selected from
In some embodiments, X2 is
In some embodiments, X2 is
In some embodiments, X2 is
In some embodiments, X2 is
In some embodiments, X2 is
In some embodiments, X2 is
In some embodiments, X2 is
In some embodiments, X2 is selected from those depicted in Table 1, below.
As defined generally above, each of X3 and X4 is independently a bivalent moiety selected from a covalent bond, —O—, —C(R)2—, —CF2—, —C(R1)F—, —S—, —S(O)—, —S(O)2—, —Si(R1)2—, —P(O)(R1)—, or —N(R)—.
In some embodiments, X3 is a covalent bond. In some embodiments, X3 is —O—. In some embodiments, X3 is —C(R)2—. In some embodiments, X3 is —CF2—. In some embodiments, X3 is —C(R1)F—. In some embodiments, X3 is —CHF—. In some embodiments, X3 is —S—. In some embodiments, X3 is —S(O)—. In some embodiments, X3 is —S(O)2—. In some embodiments, X3 is —Si(R1)2—. In some embodiments, X3 is —P(O)(R1)—. In some embodiments, X3 is —N(R)—.
In some embodiments, X3 is selected from those depicted in Table 1, below.
In some embodiments, X4 is a covalent bond. In some embodiments, X4 is —O—. In some embodiments, X4 is —C(R)2—. In some embodiments, X4 is —CF2—. In some embodiments, X4 is —CHF—. In some embodiments, X4 is —S—. In some embodiments, X4 is —S(O)—. In some embodiments, X4 is —S(O)2—. In some embodiments, X4 is —Si(R1)2—. In some embodiments, X4 is —P(O)(R1)—. In some embodiments, X4 is —N(R)—.
In some embodiments, X4 is selected from those depicted in Table 1, below.
As defined generally above, X5 is a bivalent moiety selected from a covalent bond, —O—, −S—, —CH2—, —C(R1)H—, —C(R1)CF3—, —C(R1)2—, —C(O)—, —C(NR1)—, —C(S)—, —N(R1)—, —Si(R1)2—, —P(O)(OR1)—, —P(O)(R1)—, —P(O)N(R1)2—, or
In some embodiments, X5 is a covalent bond. In some embodiments, X5 is —O—. In some embodiments, X5 is —S—. In some embodiments, X5 is —CH2—. In some embodiments, X5 is —C(R1)H—. In some embodiments, X5 is —C(R1)CF3—. In some embodiments, X5 is —CHCF3—. In some embodiments, X5 is —C(O)—. In some embodiments, X5 is —C(NR1)—. In some embodiments, X5 is —C(S)—. In some embodiments, X5 is —N(R1)—. In some embodiments, X5 is —Si(R1)2—. In some embodiments, X5 is —P(O)(R1)—. In some embodiments, X5 is —P(O)(R1)—. In some embodiments, X5 is —P(O)N(R1)2—. In some embodiments, X5 is
In some embodiments, X5 is selected from those depicted in Table 1, below.
As defined generally above, each R is independently hydrogen, deuterium, or an optionally substituted group selected from C1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur, and a 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-8 membered saturated, partially unsaturated, or heteroaryl monocyclic ring having 0-1 heteroatom, in addition to the nitrogen, independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 0-2 heteroatoms, in addition to the nitrogen, independently selected from boron, nitrogen, oxygen, silicon, or sulfur.
In some embodiments, R is hydrogen. In some embodiments, R is deuterium. In some embodiments, R is an optionally substituted C1-6 aliphatic. In some embodiments, R is an optionally substituted phenyl. In some embodiments, R is an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, R is an optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, R is an optionally substituted 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, R is an optionally substituted 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, two R groups on the same nitrogen are optionally taken together with their intervening atoms to form an optionally substituted 4-8 membered saturated, partially unsaturated, or heteroaryl monocyclic ring having 0-1 heteroatom, in addition to the nitrogen, independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, two R groups on the same nitrogen are optionally taken together with their intervening atoms to form an optionally substituted 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a Spiro heterocyclic ring having 0-2 heteroatoms, in addition to the nitrogen, independently selected from boron, nitrogen, oxygen, silicon, or sulfur.
In some embodiments, R is selected from those depicted in Table 1, below.
As defined generally above, each R1 is independently hydrogen, deuterium, halogen, —CN, —OR, —SR, —S(O)R, —S(O)2R, —N(R)2, —P(O)(R)2, —P(O)(OR)2, —P(O)(NR2)OR, —P(O)(NR2)2, —Si(OH)R2, —Si(OH)2R, —SiR3, or an optionally substituted C1-4 aliphatic, or R1 and X1 or X4 are taken together with their intervening atoms to form a 5-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or two R1 groups on the same carbon are optionally taken together with their intervening atoms to form a 3-6 membered spiro fused ring or a 4-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or two R1 groups on adjacent carbon atoms are optionally taken together with their intervening atoms to form a 3-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur.
In some embodiments, R1 is hydrogen. In some embodiments, R1 is deuterium. In some embodiments, R1 is halogen. In some embodiments, R1 is —CN. In some embodiments, le is —OR. In some embodiments, R1 is —SR. In some embodiments, R1 is —S(O)R. In some embodiments, R1 is —S(O)2R. In some embodiments, R1 is —N(R)2. In some embodiments, R1 is —Si(R)3. In some embodiments, R1 is —P(O)(R)2. In some embodiments, R1 is —P(O)(OR)2. In some embodiments, R1 is —P(O)(NR2)OR. In some embodiments, R1 is —P(O)(NR2)2. In some embodiments, R1 is —Si(OH)R2. In some embodiments, R1 is —Si(OH)2R. In some embodiments, le is an optionally substituted C1-4 aliphatic. In some embodiments, R1 and X1 or X4 are taken together with their intervening atoms to form a 5-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, two R1 groups on the same carbon are optionally taken together with their intervening atoms to form a 3-6 membered spiro fused ring or a 4-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, two R1 groups on adjacent carbon atoms are optionally taken together with their intervening atoms to form a 3-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, two R1 groups on adjacent carbon atoms are optionally taken together with their intervening atoms to form a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur.
In some embodiments, R1 is selected from hydrogen, halogen, —CN, —OR, —N(R)2, or C1-4 alkyl. In some embodiments, R1 is selected from hydrogen, halogen, —CN, or C1-4 alkyl. In some embodiments, R1 is fluoro. In some embodiments, two R1 groups on the same carbon are optionally taken together with their intervening atoms to form a 3- or 4-membered spiro fused ring.
In some embodiments, R1 is selected from those depicted in Table 1, below.
As defined generally above, each R2 is independently hydrogen, deuterium, halogen, —CN, —NO2, —OR, —SR, —N(R)2, —Si(OH)2R, —Si(OH)(R)2, —Si(R)3, —S(O)2R, —S(O)2NR2, —S(O)R, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, —N(R)S(O)2R, —N(R)S(O)2NR2, —P(O)(R)2, —P(O)(OR)2, —P(O)(NR2)OR, —P(O)(NR2)2, optionally substituted C1-6 aliphatic, optionally substituted phenyl, optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, optionally substituted 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur; or a 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur.
In some embodiments, R2 is hydrogen. In some embodiments, R2 is deuterium. In some embodiments, R2 is halogen. In some embodiments, R2 is —CN. In some embodiments, R2 is —NO2. In some embodiments, R2 is —OR. In some embodiments, R2 is —SR. In some embodiments, R2 is —N(R)2. In some embodiments, R2 is —Si(OH)2R. In some embodiments, R2 is —Si(OH)(R)2. In some embodiments, R2 is —S(O)2R. In some embodiments, R2 is —S(O)2N(R)2. In some embodiments, R2 is —S(O)R. In some embodiments, R2 is —C(O)R. In some embodiments, R2 is —C(O)OR. In some embodiments, R2 is —C(O)NR2. In some embodiments, R2 is —C(O)N(R)OR. In some embodiments, R2 is —OC(O)R. In some embodiments, R2 is —OC(O)NR2. In some embodiments, R2 is —N(R)C(O)OR. In some embodiments, R2 is —N(R)C(O)R. In some embodiments, R2 is —N(R)C(O)NR2. In some embodiments, R2 is —N(R)S(O)2R. In some embodiments, R2 is —Si(R)3. In some embodiments, R2 is —P(O)(R)2. —P(O)(OR)2. In some embodiments, R2 is —P(O)(NR2)OR. In some embodiments, R2 is —P(O)(NR2)2. In some embodiments, R2 is an optionally substituted C1-6 aliphatic. In some embodiments, R2 is an optionally substituted phenyl. In some embodiments, R2 is an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, R2 is an optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, R2 is an optionally substituted 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, R2 is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur.
In some embodiments, R2 is hydrogen, halogen, —CN, —NO2, —OR, —SR, —N(R)2, —C(O)R, —N(R)C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, —N(R)S(O)2R, optionally substituted C1-6 aliphatic, optionally substituted phenyl, an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or an optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, or sulfur; wherein R is hydrogen, C1-4 alkyl optionally substituted with 1, 2, or 3 deuterium or halogen atoms, or phenyl.
In some embodiments, R2 is hydrogen, halogen, —CN, —OR, —N(R)2, —C(O)R, —N(R)C(O)R, —C(O)OR, —C(O)NR2, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, C1-6 aliphatic optionally substituted with 1, 2, 3, 4, 5, or 6 deuterium or halogen atoms, phenyl optionally substituted with 1, 2, or 3 halogen, C1-4 alkyl, —OR, —N(R)2, or —CN groups, 4-7 membered saturated or partially unsaturated heterocyclic ring optionally substituted with a carbonyl or C1-4 alkyl group and having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 5-6 membered heteroaryl ring optionally substituted with 1, 2, or 3 halogen, C1-4 alkyl, —OR, —N(R)2, or —CN groups and having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein R is hydrogen, C1-4 alkyl optionally substituted with 1, 2, or 3 deuterium or halogen atoms, or phenyl.
In some embodiments, R2 is C1-4 aliphatic optionally substituted with 1, 2, 3, 4, 5, or 6 deuterium or halogen atoms.
In some embodiments, R2 is methyl. In some embodiments, R2 is ethyl. In some embodiments, R2 is isopropyl. In some embodiments, R2 is phenyl. In some embodiments, R2 is fluoro. In some embodiments, R2 is chloro. In some embodiments, R2 is —CF3. In some embodiments, R2 is —NH2. In some embodiments, R2 is —NHC(O)CH3. In some embodiments, R2 is —OCH3. In some embodiments, R2 is —C(O)OH. In some embodiments, R2 is —C(O)Et. In some embodiments, R2 is —C(O)t-Bu. In some embodiments, R2 is —C(O)NH2.
In some embodiments, R2 is selected from those depicted in Table 1, below.
As defined generally above, L1 is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-6 hydrocarbon chain, wherein 1-2 methylene units of L1 are independently and optionally replaced by —O—, —NR3—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —Si(R)2—, —P(O)(R1)—, —S(O)—, —S(O)2—, —NR3S(O)2—, —S(O)2NR3—, —NR3C(O)—, —C(O)NR3—, —OC(O)NR3—, —NR3C(O)O—
provided that L1 is not a covalent bond, —CH2—, —C(O)O—, —C(O)OCH2—, —CH2C(O)—, —C(O)CH2—, —NR3C(O)—, —C(O)NR3—, or —CH2CH2— when Ring A is
and X1 is —C(O)— or Ring A is
and X2 is
In some embodiments, L1 is a covalent bond. In some embodiments, L1 is a bivalent, saturated or unsaturated, straight or branched C1-6 hydrocarbon chain. In some embodiments, L1 is a bivalent, saturated or unsaturated, straight or branched C1-6 hydrocarbon chain, wherein 1-2 methylene units of L1 are independently and optionally replaced by —O—, —NR3—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —Si(R)2—, —P(O)(R1)—, —S(O)—, —S(O)2—, —NR3S(O)2—, —S(O)2NR3—, —NR3C(O)—, —C(O)NR3—, —OC(O)NR3—, —NR3C(O)O—,
In some embodiments, L1 is not a covalent bond, —CH2—, —C(O)O—, —C(O)OCH2—, —CH2C(O)—, —C(O)CH2—, —NR3C(O)—, —C(O)NR3—, or —CH2CH2— when Ring A is
and X1 is —C(O)— or Ring A is
and X2 is
In some embodiments, L1 is a covalent bond or a bivalent, saturated, straight or branched C1-6 hydrocarbon chain, wherein 1-2 methylene units of L1 are independently and optionally replaced by —O—, —S—, —S(O)—, —S(O)2—,
In some embodiments, L1 is a bivalent, saturated, straight C1-6 hydrocarbon chain. In some embodiments, L1 is a bivalent, saturated, straight C1-3 hydrocarbon chain. In some embodiments, L1 is a bivalent, saturated, straight C2-3 hydrocarbon chain. In some embodiments, L1 is —CH2—, —O—, —N(R)—, —S—, —OCH2—, —SCH2—, —CH2O—, —CH2O—, —OCH2O—, —SCH2O—, —OCH2S—, —SCH2S—, —SCH2OC(O)—, —N(R)CH2O—, —OCH2N(R)—, —OCH2CH2O—, —SCH2CH2O—, —OCH2CH2S—, or —SCH2CH2S—.
In some embodiments, L1 is —CH2—. In some embodiments, L1 is —N(CH3)C(O)— or —(O)CN(CH3)—.
In some embodiments, L1 is other than a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-6 hydrocarbon chain, wherein 1-2 methylene units of L1 are independently and optionally replaced by —O—, —NR3—, —OC(O)—, —C(O)O—, —C(O)—, —NR3S(O)2—, —S(O)2NR3—, —N(R)C(O)—, —C(O)N(R)—, or —NR3C(O)O— when Ring A is
and X1 is —C(O)—, Ring A is
and X2 is
Ring A is
and X2 is
Ring A is
Ring A is
and X1 is —C(O)— or —CH2—, or Ring A is
and X2 is
In some embodiments, L1 is other than a covalent bond when Ring A is
and X1 is —C(O)—. In some embodiments, L1 is other than a covalent bond when Ring A is
and X2 is
In some embodiments, L1 is other than a covalent bond when Ring A is
and X2 is
In some embodiments, L1 is other than a covalent bond when Ring A is
In some embodiments, L1 is other than a covalent bond when Ring A is
and X1 is —C(O)— or —CH2—. In some embodiments, L1 is other than a covalent bond when Ring A is
and X2 is
In some embodiments, L1 is other than a bivalent, saturated or unsaturated, straight or branched C1-6 hydrocarbon chain, wherein 1-2 methylene units of L1 are independently and optionally replaced by —O—, —NR3—, —OC(O)—, —C(O)O—, —C(O)—, —NR3S(O)2—, —S(O)2NR3—, —N(R)C(O)—, —C(O)N(R)—, or —NR3C(O)O— when Ring A is
and X1 is —C(O)—. In some embodiments, L1 is other than a bivalent, saturated or unsaturated, straight or branched C1-6 hydrocarbon chain, wherein 1-2 methylene units of L1 are independently and optionally replaced by —O—, —NR3—, —OC(O)—, —C(O)O—, —C(O)—, —NR3S(O)2—, —S(O)2NR3—, —N(R)C(O)—, —C(O)N(R)—, or —NR3C(O)O— when Ring A is
and X2 is
In some embodiments, L1 is other than a bivalent, saturated or unsaturated, straight or branched C1-6 hydrocarbon chain, wherein 1-2 methylene units of L1 are independently and optionally replaced by —O—, —NR3—, —OC(O)—, —C(O)O—, —C(O)—, —NR3S(O)2—, —S(O)2NR3—, —N(R)C(O)—, —C(O)N(R)—, or —NR3C(O)O— when Ring A is
and X2 is
In some embodiments, L1 is other than a bivalent, saturated or unsaturated, straight or branched C1-6 hydrocarbon chain, wherein 1-2 methylene units of L1 are independently and optionally replaced by —O—, —NR3—, —OC(O)—, —C(O)O—, —C(O)—, —NR3S(O)2—, —S(O)2NR3—, —N(R)C(O)—, —C(O)N(R)—, or —NR3C(O)O— when Ring A is
In some embodiments, L1 is other than a bivalent, saturated or unsaturated, straight or branched C1-6 hydrocarbon chain, wherein 1-2 methylene units of L1 are independently and optionally replaced by —O—, —NR3—, —OC(O)—, —C(O)O—, —C(O)—, —NR3S(O)2—, —S(O)2NR3—, —N(R)C(O)—, —C(O)N(R)—, or —NR3C(O)O— when Ring A is
and X1 is —C(O)— or —CH2—. In some embodiments, L1 is other than a bivalent, saturated or unsaturated, straight or branched C1-6 hydrocarbon chain, wherein 1-2 methylene units of L1 are independently and optionally replaced by —O—, —NR3—, —OC(O)—, —C(O)O—, —C(O)—, —NR3S(O)2—, —S(O)2NR3—, —N(R)C(O)—, —C(O)N(R)—, or —NR3C(O)O— when Ring A is
and X2 is
In some embodiments, L1 is selected from those depicted in Table 1, below.
As defined generally above, L2 is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-50 hydrocarbon chain, wherein 0-6 methylene units of L2 are independently replaced by -Cy-, —O—, —NR—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —S(O)—, —S(O)2—, —NRS(O)2—, —S(O)2NR—, —NRC(O)—, —C(O)NR—, —OC(O)NR—, —NRC(O)O—,
wherein: each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, an 8-10 membered bicyclic arylenyl, a 4-7 membered saturated or partially unsaturated carbocyclylenyl, a 4-7 membered saturated or partially unsaturated spiro carbocyclylenyl, an 8-10 membered bicyclic saturated or partially unsaturated carbocyclylenyl, a 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In some embodiments, L2 is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-50 hydrocarbon chain, wherein 0-6 methylene units of L2 are independently replaced by -Cy-, —O—, —NR—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —S(O)—, —S(O)2—, —NRS(O)2—, —S(O)2NR—, —NRC(O)—, —C(O)NR—, —OC(O)NR—, —NRC(O)O—,
wherein: each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, an 8-10 membered bicyclic arylenyl, a 4-7 membered saturated or partially unsaturated carbocyclylenyl, a 4-7 membered saturated or partially unsaturated spiro carbocyclylenyl, an 8-10 membered bicyclic saturated or partially unsaturated carbocyclylenyl, a 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In some embodiments, L2 is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-50 hydrocarbon chain, wherein 0-6 methylene units of L2 are independently replaced by -Cy-, —O—, —NR—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —S(O)—, —S(O)2—, —NRS(O)2—, —S(O)2NR—, —NRC(O)—, —C(O)NR—, —OC(O)NR—, —NRC(O)O—,
wherein: each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, an 8-10 membered bicyclic arylenyl, a 4-7 membered saturated or partially unsaturated carbocyclylenyl, a 4-7 membered saturated or partially unsaturated spiro carbocyclylenyl, an 8-10 membered bicyclic saturated or partially unsaturated carbocyclylenyl, a 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur.
In some embodiments, each -Cy- is independently an optionally substituted bivalent phenylenyl. In some embodiments, each -Cy- is independently an optionally substituted 8-10 membered bicyclic arylenyl. In some embodiments, each -Cy- is independently an optionally substituted 4-7 membered saturated or partially unsaturated carbocyclylenyl. In some embodiments, each -Cy- is independently an optionally substituted 4-7 membered saturated or partially unsaturated spiro carbocyclylenyl. In some embodiments, each -Cy- is independently an optionally substituted 8-10 membered bicyclic saturated or partially unsaturated carbocyclylenyl. In some embodiments, each -Cy- is independently an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, each -Cy- is independently an optionally substituted 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, each -Cy- is independently an optionally substituted 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, each -Cy- is independently an optionally substituted 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, each -Cy- is independently an optionally substituted 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur.
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, -Cy- is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
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In some embodiments, L2 is
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In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
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In some embodiments, L2 is
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In some embodiments, L2 is
In some embodiments, L2 is
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In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
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In some embodiments, L2 is
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In some embodiments, L2 is
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In some embodiments, L2 is
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In some embodiments, L2 is
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In some embodiments, L2 is
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In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
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In some embodiments, L2 is
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In some embodiments, L2 is
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In some embodiments, L2 is
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In some embodiments, L2 is
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In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
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In some embodiments, L2 is
In some embodiments, L2 is
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In some embodiments, L2 is
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In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
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In some embodiments, L2 is
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In some embodiments, L2 is
In some embodiments, L2 is
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In some embodiments, L2 is
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In some embodiments, L2 is
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In some embodiments, L2 is
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In some embodiments, L2 is
In some embodiments, L2 is
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some embodiments, L2 is
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some embodiments, L2 is
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In some embodiments, L2 is
In some embodiments, L is
In some embodiments, L is
In some embodiments, L is
In some embodiments, L2 is
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In some embodiments, L2 is
In some embodiments, L2 is
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In some some embodiments, L2 is
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In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L is
In some embodiments, L2 is
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In some embodiments, L2 is
In
In some embodiments, L2 is
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In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
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In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, 2L is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is
In some embodiments, L2 is selected from those depicted in Table 1, below.
As defined generally above, each R3 is independently hydrogen, deuterium, or an optionally substituted C1-4 aliphatic.
In some embodiments, R3 is hydrogen. In some embodiments, R3 is deuterium. In some embodiments, R3 is an optionally substituted C1-4 aliphatic.
In some embodiments, R3 is methyl.
In some embodiments, R3 is selected from those depicted in Table 1, below.
As defined generally above, Ring B is a 3 to 7-membered saturated or partially unsaturated carbocyclic ring, phenyl, 8-10 membered bicyclic carbocyclic aromatic ring, 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur; wherein Ring B is optionally further substituted with 1-2 oxo groups.
In some embodiments, Ring B is a 3 to 7-membered saturated or partially unsaturated carbocyclic ring. In some embodiments, Ring B is phenyl. In some embodiments, Ring B is an 8-10 membered bicyclic carbocyclic aromatic ring. In some embodiments, Ring B is a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, Ring B is a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Ring B is a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, Ring B is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, Ring B is optionally further substituted with 1-2 oxo groups.
In some embodiments, Ring B is selected from
phenylenyl, pyridylenyl, pyrimidylenyl
triazolylenyl,
In some embodiments,
is selected from
In some embodiments,
is selected from
In some embodiments, Ring B is selected from those depicted in Table 1, below.
As defined generally above, TBM is a target binding moiety.
In some embodiments, TBM is a target binding moiety.
In some embodiments. TBM binds to a protein selected from those listed herein.
In some embodiments, TBM is selected from one of the drugs listed in Table 2, wherein the drug is attached to
at any modifiable carbon, oxygen, sulfur or nitrogen atom.
In some embodiments, TBM is
In some embodiments, TBM
In some embodiments, TBM is
In some embodiments, TBM is
In some embodiments, TBM is
In some embodiments, TBM is
In some embodiments, TBM is
In some embodiments, TBM is
In some embodiments, TBM is
In some embodiments, TBM is
In some embodiments, TBM is
In some embodiments, TBM is
In some embodiments, TBM is
In some embodiments, TBM is
In some embodiments, TBM is selected from those depicted in Table 1, below.
As defined generally above, m is 0, 1, 2, 3 or 4.
In some embodiments, m is 0, 1, 2, 3 or 4.
In some embodiments, m is selected from those depicted in Table 1, below.
As defined generally above, n is 0, 1, 2, 3 or 4.
In some embodiments, n is 0, 1, 2, 3 or 4.
In some embodiments, n is selected from those depicted in Table 1, below.
As defined generally above, each of p is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
In some embodiments. p is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
In some embodiments, p is selected from those depicted in Table 1, below.
In some embodiments, the present invention provides a compound of Formula I, wherein Ring A is
and L1 is —O— or —S—, thereby forming a compound of Formula II-a or II-b:
or a pharmaceutically acceptable salt thereof, wherein each of Ring B, R2, n, L2, and TBM is as defined above and described in embodiments herein, both singly and in combination.
In some embodiments, the present invention provides a compound of Formula I, wherein Ring A is
and L1 is —S(O)— or —S(O)2—, thereby forming a compound of Formula II-b′ or II-b″:
or a pharmaceutically acceptable salt thereof, wherein each of Ring B, R2, n, L2, and TBM is as defined above and described in embodiments herein, both singly and in combination.
In some embodiments, the present invention provides a compound of Formula II-b′″:
or a pharmaceutically acceptable salt thereof, wherein
- each R1 is independently hydrogen, deuterium, halogen, —CN, —OR, —SR, —S(O)R, —S(O)2R, —N(R)2, —Si(R)3, —P(O)(R)2, or an optionally substituted C1-4 aliphatic; or
- two R1 groups on the same carbon are optionally taken together with their intervening atoms to form a 3-6 membered spiro fused ring or a 4-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- two R1 groups on adjacent carbon atoms are optionally taken together with their intervening atoms to form a 3-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- each R is independently hydrogen, deuterium, or an optionally substituted group selected from C1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur, and a 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur; or
- two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-8 membered saturated, partially unsaturated, or heteroaryl monocyclic ring having 0-1 heteroatom, in addition to the nitrogen, independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 0-2 heteroatoms, in addition to the nitrogen, independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- each R2 is independently hydrogen, deuterium, halogen, —CN, —NO2, —OR, —SR, —NR2, —Si(OH)2R, —Si(OH)(R)2, —Si(R)3, —S(O)2R, —S(O)2NR2, —S(O)R, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, —N(R)S(O)2R, —N(R)S(O)2NR2, —P(O)(OR)2, —P(O)(NR2)OR, —P(O)(NR2)2, optionally substituted C1-6 aliphatic, optionally substituted phenyl, optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, optionally substituted 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur; or a 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- L2 is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-50 hydrocarbon chain, wherein 0-6 methylene units of L2 are independently replaced by -Cy-, —O—, —NR—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —Si(R1)2—, —P(O)(R1)—, —S(O)—, —S(O)2—, —NRS(O)2—, —S(O)2NR—, —NRC(O)—, —C(O)NR—, —OC(O)NR—, —NRC(O)O—,
wherein:
- each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, 8-10 membered bicyclic arylenyl, 4-7 membered saturated or partially unsaturated carbocyclylenyl, 4-7 membered saturated or partially unsaturated spiro carbocyclylenyl, 8-10 membered bicyclic saturated or partially unsaturated carbocyclylenyl, 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- Ring B is selected from a 3 to 7-membered saturated or partially unsaturated carbocyclic ring, phenyl, 8-10 membered bicyclic carbocyclic aromatic ring, 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur; wherein Ring B is optionally further substituted with 1-2 oxo groups;
- TBM is a target binding moiety;
- m is 0, 1, 2, 3, or 4; and
- n is 0, 1, 2, 3, or 4.
In some embodiments, the present invention provides a compound of formula I, wherein Ring A is
and L1 is a covalent bond, thereby forming a compound of Formula III-a
III-a
or a pharmaceutically acceptable salt thereof, wherein each of Ring B, R2, n, L2, and TBM is as defined above and described in embodiments herein, both singly and in combination.
In some embodiments, the present invention provides a compound of Formula I, wherein Ring A is
and L1 is a covalent bond or —CH2—, hereby forming a compound of Formula IV-a, IV-b, IV-c, or IV-d:
or a pharmaceutically acceptable salt thereof, wherein each of Ring B, R2, n, L2, and TBM is as defined above and described in embodiments herein, both singly and in combination.
In some embodiments, the present invention provides a compound of Formula I, wherein Ring A is
and L1 is a covalent bond, hereby forming a compound of Formula V-a, V-b, V-c, V-d, or V-e:
or a pharmaceutically acceptable salt thereof, wherein:
- each R2 is independently hydrogen, deuterium, halogen, —CN, —NO2, —OR, —SR, —N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, —N(R)S(O)2R, —Si(R1)3, —P(O)(R1)2, optionally substituted C1-6 aliphatic, optionally substituted phenyl, an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or an optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- each R is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur; or
- two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- each R1 is independently hydrogen, deuterium, halogen, —CN, —OR, —SR, —S(O)R, —S(O)2R, —N(R)2, —Si(R)3, —P(O)(R)2, or an optionally substituted C1-4 aliphatic; or
- two R1 groups on the same carbon are optionally taken together with their intervening atoms to form a 3-6 membered spiro fused ring; or
- two R1 groups on adjacent carbon atoms are optionally taken together with their intervening atoms to form a 3-6 membered saturated, partially unsaturated, or aryl fused ring having heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- L2 is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-50 hydrocarbon chain, wherein 0-6 methylene units of L2 are independently replaced by -Cy-, —O—, —NR—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —Si(R1)2—, —P(O)(R1)—, —S(O)—, —S(O)2—, —NRS(O)2—, —S(O)2NR—, —NRC(O)—, —C(O)NR—, —OC(O)NR—, —NRC(O)O—,
wherein:
- each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, 8-10 membered bicyclic arylenyl, 4-7 membered saturated or partially unsaturated carbocyclylenyl, 4-7 membered saturated or partially unsaturated spiro carbocyclylenyl, 8-membered bicyclic saturated or partially unsaturated carbocyclylenyl, 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- Ring B is selected from a 4 to 7-membered saturated or partially unsaturated carbocyclic ring, phenyl, an 8-10 membered bicyclic carbocyclic aromatic ring, a 5 to 7-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, a 5-6-membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, wherein Ring B is optionally further substituted with 1-2 oxo groups;
- TBM is a target binding moiety; and
- n is 0, 1, 2, 3, or 4.
In some embodiments, the present invention provides a compound of Formula III-a′, V-a′, V-b′, V-c′, or V-f:
or a pharmaceutically acceptable salt thereof, wherein:
- each of X1, X5, and X6 is independently a bivalent moiety selected from a covalent bond, —O—, —S—, —C(R1)CF3—, —C(R1)2—, —C(O)—, —N(R1)—, —C(NR1)—, —C(S)—, —Si(R1)2—, —P(O)(R1)—, —P(O)(OR1)—, —P(O)N(R1)2—, or
- X3 is a bivalent moiety selected from a covalent bond, —O—, —S—, —C(R1)F—, —CF2—, —C(R1)2—, —S(O)—, —S(O)2—, —Si(R1)2—, —P(O)(R1)—, or —N(R)—;
- each R is independently hydrogen, deuterium, or an optionally substituted group selected from C1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur, and a 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur; or
- two R groups on the same nitrogen are optionally taken together with their intervening atoms to form a 4-8 membered saturated, partially unsaturated, or heteroaryl monocyclic ring having 0-1 heteroatom, in addition to the nitrogen, independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 0-2 heteroatoms, in addition to the nitrogen, independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- each R1 is independently hydrogen, deuterium, halogen, —CN, —OR, —SR, —S(O)R, —S(O)2R, —N(R)2, —P(O)(OR)2, —P(O)(NR2)OR, —P(O)(NR2)2, —Si(OH)R2, —Si(OH)2R, —SiR3, or an optionally substituted C1-4 aliphatic; or
- R1 and X1 are taken together with their intervening atoms to form a 5-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- two R1 groups on the same carbon are optionally taken together with their intervening atoms to form a 3-6 membered spiro fused ring or a 4-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- two R1 groups on adjacent carbon atoms are optionally taken together with their intervening atoms to form a 3-7 membered saturated, partially unsaturated, carbocyclic ring or heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- each R2 is independently hydrogen, deuterium, halogen, —CN, —NO2, —OR, —SR, —NR2, —Si(OH)2R, —Si(OH)(R)2, —Si(R)3, —S(O)2R, —S(O)2NR2, —S(O)R, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, —N(R)S(O)2R, —N(R)S(O)2NR2, —P(O)(OR)2, —P(O)(NR2)OR, —P(O)(NR2)2, optionally substituted C1-6 aliphatic, optionally substituted phenyl, optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, optionally substituted 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur; or a 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- L1 is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-6 hydrocarbon chain, wherein 1-2 methylene units of L1 are independently and optionally replaced by —O—, —NR3—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —Si(R1)2—, —P(O)(R1)—, —P(O)(OR)—, —P(O)(NR2)—, —S(O)—, —S(O)2—, —NR3S(O)2—, —S(O)2NR3—, —NR3C(O)—, —C(O)NR3—, —OC(O)NR3—, —NR3C(O)O—,
- L2 is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-50 hydrocarbon chain, wherein 0-6 methylene units of L2 are independently replaced by -Cy-, —O—, —NR—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —Si(R)2—, —P(O)(R1)—, —S(O)—, —S(O)2—, —NRS(O)2—, —S(O)2NR—, —NRC(O)—, —C(O)NR—, —OC(O)NR—, —NRC(O)O—,
wherein:
- each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, 8-10 membered bicyclic arylenyl, 4-7 membered saturated or partially unsaturated carbocyclylenyl, 4-7 membered saturated or partially unsaturated spiro carbocyclylenyl, 8-membered bicyclic saturated or partially unsaturated carbocyclylenyl, 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 8-membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur;
- each R3 is independently hydrogen, deuterium, or optionally substituted C1-4 aliphatic;
- Ring B is selected from a 3 to 7-membered saturated or partially unsaturated carbocyclic ring, phenyl, 8-10 membered bicyclic carbocyclic aromatic ring, 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, 7-13 membered saturated, partially unsaturated, bridged heterocyclic ring, or a spiro heterocyclic ring having 1-3 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur; wherein Ring B is optionally further substituted with 1-2 oxo groups;
- TBM is a target binding moiety;
- m is 0, 1, 2, 3, or 4;
- n is 0, 1, 2, 3, or 4; and
- each of p is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
In preferred aspects of the invention, the TBM group is a group, which binds to target proteins. Targets of the TBM group are numerous in kind and are selected from proteins that are expressed in a cell such that at least a portion of the sequences is found in the cell and may bind to a TBM group. The term“protein” includes oligopeptides and polypeptide sequences of sufficient length that they can bind to a TBM group according to the present invention. Any protein in a eukaryotic system, as described herein, are targets for ubiquitination mediated by the compounds according to the present invention.
TBM groups according to the present invention include, for example, include any moiety which binds to a protein specifically (binds to a target protein) and includes the following non-limiting examples of small molecule target protein moieties: Hsp90 inhibitors, kinase inhibitors, HDM2 & MDM2 inhibitors, compounds targeting Human BET Bromodomain-containing proteins, HDAC inhibitors, human lysine methyltransferase inhibitors, angiogenesis inhibitors, nuclear hormone receptor compounds, immunosuppressive compounds, and compounds targeting the aryl hydrocarbon receptor (AHR), among numerous others. The compositions described below exemplify some of the members of these nine types of small molecule target protein binding moieties. Such small molecule target protein binding moieties also include pharmaceutically acceptable salts, enantiomers, solvates and polymorphs of these compositions, as well as other small molecules that may target a protein of interest. These binding moieties are linked to the ubiquitin ligase binding moiety preferably through a linker in order to present a target protein (to which the protein target moiety is bound) in proximity to the ubiquitin ligase for ubiquitination and degradation.
Any protein, which can bind to a target binding moiety or TBM group and acted on or degraded by an ubiquitin ligase is a target protein according to the present invention. In general, target proteins may include, for example, structural proteins, receptors, enzymes, cell surface proteins, proteins pertinent to the integrated function of a cell, including proteins involved in catalytic activity, aromatase activity, motor activity, helicase activity, metabolic processes (anabolism and catabolism), antioxidant activity, proteolysis, biosynthesis, proteins with kinase activity, oxidoreductase activity, transferase activity, hydrolase activity, lyase activity, isomerase activity, ligase activity, enzyme regulator activity, signal transducer activity, structural molecule activity, binding activity (protein, lipid carbohydrate), receptor activity, cell motility, membrane fusion, cell communication, regulation of biological processes, development, cell differentiation, response to stimulus, behavioral proteins, cell adhesion proteins, proteins involved in cell death, proteins involved in transport (including protein transporter activity, nuclear transport, ion transporter activity, channel transporter activity, carrier activity, permease activity, secretion activity, electron transporter activity, pathogenesis, chaperone regulator activity, nucleic acid binding activity, transcription regulator activity, extracellular organization and biogenesis activity, translation regulator activity. Proteins of interest can include proteins from eurkaryotes and prokaryotes including humans as targets for drug therapy, other animals, including domesticated animals, microbials for the determination of targets for antibiotics and other antimicrobials and plants, and even viruses, among numerous others.
TBM (or target binding moiety) is a small molecule which is capable of binding to or binds to a target protein of interest.
Some embodiments of the present application relate to TBMs which include but are not limited to Hsp90 inhibitors, kinase inhibitors, MDM2 inhibitors, compounds targeting Human BET Bromodomain-containing proteins, compounds targeting cytosolic signaling protein FKBP12, HDAC inhibitors, human lysine methyltransferase inhibitors, angiogenesis inhibitors, immunosuppressive compounds, and compounds targeting the aryl hydrocarbon receptor (AHR).
In some embodiments, TBM is a BRD ligand selected from
wherein R denotes attachment to
or
In some embodiments, TBM is a CREBBP ligand selected from
wherein R denotes attachment to
or
X is N or C; and n is 0 to 8.
In some embodiments, TBM is a SMARCA4/PB1/SMARCA2 ligand selected from
wherein R denotes attachment to
or
X is N or C; and n is 0 to 8.
In some embodiments, TBM is a TRIM24/BRPF1 ligand selected from
wherein R denotes attachment to
or
and n is 0 to 8.
In some embodiments, TBM is a glucocorticoid receptor ligand selected from
wherein R denotes attachment to
or
In some embodiments, TBM is a estrogen/androgen receptor ligand selected from
wherein R denotes attachment to
or
In some embodiments, TBM is a DOT1L ligand selected from
wherein R denotes attachment to
X is N or C; and n is 0-8.
In some embodiments, TBM is a BRAF ligand selected from
wherein R denotes attachment to
or
In some embodiments, TBM is a Ras ligand selected from
wherein R denotes attachment to
or
In some embodiments, TBM is a RasG12C ligand selected from
wherein R denotes attachment to
or
In some embodiments, TBM is a Her3 ligand selected from
wherein R denotes attachment to
or
and R′ is —CH2CH3 or —CH═CH2.
In some embodiments, TBM is a Bcl-2/Bcl-XL ligand selected from
wherein R denotes attachment to
or
In some embodiments, TBM is an HDAC ligand selected from
wherein R denotes attachment to
or
In some embodiments, TBM is a PPAR-gamma ligand selected from
wherein R denotes attachment to
or
In some embodiments, TBM is selected from
wherein
is attached to a modifiable carbon, oxygen, nitrogen or sulfur atom.
In some embodiments, TBM is an Abl, KRAS, SHP2, cRAF, MerTK or PRMT5 ligand that are selected from the following non-limiting examples:
wherein
or
is attached to a modifiable carbon, oxygen, nitrogen or sulfur atom.
In some embodiments, TBM is a KRAS ligand selected from
wherein
or
is attached to a modifiable carbon, oxygen, nitrogen or sulfur atom.
In some embodiments, a TBM moiety is selected from PTM moieties as recited in WO 2016/197032 the entirety of each of which is herein incorporated by reference. In some embodiments, a TBM moiety is selected from such inhibitors as described in WO 2016/197032 at paragraphs [00116] through [00173] through wherein the recitation of a “Linker” moiety in WO 2016/197032 corresponds to the -L- group as defined and described herein.
Exemplary compounds of the invention are set forth in Table 1, below.
TABLE 1
Exemplary Compounds
Compound
Number Structure
I-1
I-2
I-3
I-4
I-5
I-6
I-7
I-8
I-9
I-10
I-11
I-12
I-13
I-14
I-15
In some embodiments, the method employs a compound set forth in Table 1, above, or a pharmaceutically acceptable salt thereof.
In some embodiments, TBM is one of the compounds in Table 2, below, wherein
is attached to a modifiable carbon, oxygen, nitrogen or sulfur atom.
TABLE 2
Exemplary Drugs with Disease Indications and Gene Identifier for the
Target Protein
Drug Name Indication(s) Gene
3196 anticholesterolaemic agent THRB
Posiphen for treatment of Alzheimer's disease APP
Posiphen for treatment of Alzheimer's disease BACE1
MBO7133 (cytarabine prodrug) antineoplastic agent POLB
4SC-202 antineoplastic agent HDAC1
4SC-202 antineoplastic agent HDAC2
4SC-202 antineoplastic agent HDAC3
4SC-202 antineoplastic agent HDAC8
4SC-202 antineoplastic agent FLT3
4SC-202 antineoplastic agent VEGFA
4SC-205 antineoplastic agent KIF11
768974 antiosteoporotic agent PTH1R
7a-methyl-19- Hormone replacement, male AR
nortestosterone, MENT contraceptive
A-007 antineoplastic agent ESR1
A-007 antineoplastic agent ESR2
oxybutynin for treatment of incontinence CHRM1
oxybutynin for treatment of incontinence CHRM2
oxybutynin for treatment of incontinence CHRM3
Testosterone hormone replacement AR
ABC294640 antineoplastic agent SPHK1
ABC294640 antineoplastic agent SPHK2
Aripiprazole antipsychotic agent DRD2
Aripiprazole antipsychotic agent HTR1A
Aripiprazole antipsychotic agent HTR2A
pacl*taxel antineoplastic agent BCL2
pacl*taxel antineoplastic agent TUBB1
navitoclax, ABT-263 antineoplastic agent BCL2
navitoclax, ABT-263 antineoplastic agent BCL2L1
navitoclax, ABT-263 antineoplastic agent BCL2L2
fenofibrate antidyslipidaemic agent PPARA
Linifanib antineoplastic agent CSF1R
Linifanib antineoplastic agent FLT1
Linifanib antineoplastic agent FLT3
Linifanib antineoplastic agent FLT4
Linifanib antineoplastic agent KDR
Linifanib antineoplastic agent KIT
Linifanib antineoplastic agent PDGFRB
Linifanib antineoplastic agent RET
Linifanib antineoplastic agent TIE2
AC-201 antidiabetic IL1B
AC-201 antidiabetic IL1RN
quizartinib antineoplastic agent FLT3
AC430 antiinflammatory JAK2
agent, antineoplastic agent
AC480 antineoplastic agent EGFR
AC480 antineoplastic agent ERBB2
AC480 antineoplastic agent ERBB3
AC480 antineoplastic agent ERBB4
acamprosate for treatment of alcohol-dependance GRIN3A
acamprosate antineoplastic agent GRM5
toremifene antineoplastic agent, SERM ESR1
acarbose antidiabetic AMY2A
acarbose antidiabetic GAA
acarbose antidiabetic MGAM
acarbose antidiabetic SI
organic nitrate + 1-arginine vasodilator NOS3
Acccretropin for treatment of turner's syndrome GHR
rabeprazole Proton pump inhibitor ATP4A
aclidinium bronchodilator CHRM1
aclidinium bronchodilator CHRM2
aclidinium bronchodilator CHRM3
aclidinium bronchodilator CHRM4
aclidinium bronchodilator CHRM5
acotiamide for treatment of functional dyspepsia ACHE
ACP-001 hormone replacement GHR
ACP-104 antipsychotic agent CHRM1
ACP-104 antipsychotic agent DRD2
ACP-104 antipsychotic agent DRD3
ACP-104 antipsychotic agent HTR2A
ACTB1003 antineoplastic agent FGFR1
ACTB1003 antineoplastic agent FGFR2
ACTB1003 antineoplastic agent FGFR3
ACTB1003 antineoplastic agent FGFR4
ACTB1003 antineoplastic agent RPS6KB1
ACY-1215 antineoplastic agent HDAC6
AD 337 analgesic, for treatment of SLC6A2
fibromyalgia
AD 337 analgesic, for treatment of SLC6A4
fibromyalgia
fentanyl analgesic OPRD1
fentanyl analgesic OPRM1
theophylline bronchodilator ADORA1
theophylline bronchodilator ADORA2A
theophylline bronchodilator ADORA2B
theophylline bronchodilator PDE3A
theophylline bronchodilator PDE4A
theophylline bronchodilator PDE4B
theophylline bronchodilator PDE5A
ADL5747 analgesic OPRD1
ADL5859 analgesic OPRD1
ADL5945 motilitant OPRM1
ADL7445 motilitant OPRM1
capsaicin analgesic TRPV1
fluticasone propionate bronchodilator NR3C1
salmeterol bronchodilator ADRB2
ADX10059 antimigraine agent, for treatment of GRM5
gastroesophageal reflux disease
ADX415 antihypertensive agent ADRA2A
ADX-71149 antipsychotic GRM2
agent, antidepressant, anxiolytic
fentanyl analgesic OPRD1
fentanyl analgesic OPRM1
AES-103 for treatment of sickle-cell disease HBB
doxorubicin antineoplastic agent TOP2A
AEZS-112, ZEN-012 antineoplastic agent TOP2A
AEZS-112, ZEN-012 antineoplastic agent TUBB
AEZS-112, ZEN-012 antineoplastic agent TUBB1
Afamelanotide dermatological agent MC1R
afatinib antineoplastic agent EGFR
afatinib antineoplastic agent ERBB2
ethinyl estradiol contraceptive ESR1
levonorgestrel contraceptive ESR1
levonorgestrel contraceptive PGR
levonorgestrel contraceptive SRD5A1
mecamylamine motilitant CHRNA2
AGI-1067, succinobucol antiatherosclerosis agent VCAM1
AGIX-4207 antiinflammatory agent, DMARD unknown
AGN-214868 analgesic, neuralgia ADRA1A
AGN-214868 analgesic, neuralgia ADRA1B
AGN-214868 analgesic, neuralgia ADRA1D
AGN-214868 analgesic, neuralgia ADRA2A
AGN-214868 analgesic, neuralgia ADRA2B
AGN-214868 analgesic, neuralgia ADRA2C
agomelatine antidepressant MTNR1B
agomelatine antidepressant HTR2B
agomelatine antidepressant HTR2C
agomelatine antidepressant MTNR1A
hydroxychloroquine antirheumatic agent TLR7
hydroxychloroquine antirheumatic agent TLR9
pacl*taxel antineoplastic agent BCL2
pacl*taxel antineoplastic agent TUBB1
AIKO-150 opioid antagonist OPRM1
AIR645 antiasthmatic agent IL4RA
AKB-6548 for treatment of anaemia EGLN1
AKB-6548 for treatment of anaemia EGLN2
AKL-0707 hormone replacement GHRH
ALB109564(a) antineoplastic agent TUBB
ALB-127158(a) antiobesity agent MCHR1
salbutamol bronchodilator ADRB2
aleglitazar cardiovascular agent PPARA
aleglitazar cardiovascular agent PPARG
alfuzosin for treatment of benign prostatic ADRA1A
hyperplasia
alfuzosin for treatment of benign prostatic ADRA1B
hyperplasia
alfuzosin for treatment of benign prostatic ADRA1D
hyperplasia
lidocaine anesthetic SCN10A
lidocaine anesthetic SCN5A
lidocaine anesthetic SCN9A
pemetrexed antineoplastic agent DHFR
pemetrexed antineoplastic agent GART
pemetrexed antineoplastic agent TYMS
aliskiren antihypertensive agent REN
aliskiren antihypertensive agent REN
amlodipine antihypertensive agent CACNA1C
amlodipine antihypertensive agent CACNA1D
amlodipine antihypertensive agent CACNA1S
amlodipine antihypertensive agent CACNA2D1
amlodipine antihypertensive agent CACNB2
Alitretionine antineoplastic agent RARA
Alitretionine antineoplastic agent RARB
Alitretionine antineoplastic agent RARG
Alitretionine antineoplastic agent RXRA
Alitretionine antineoplastic agent RXRB
Alitretionine antineoplastic agent RXRG
Alitretionine antineoplastic agent RARA
Alitretionine antineoplastic agent RARB
Alitretionine antineoplastic agent RARG
Alitretionine antineoplastic agent RXRA
Alitretionine antineoplastic agent RXRB
Alitretionine antineoplastic agent RXRG
ALKS 33 for treatment of alcohol OPRD1
dependance, antidepressant
ALKS 33 for treatment of alcohol OPRK1
dependance, antidepressant
ALKS 33 for treatment of alcohol OPRM1
dependance, antidepressant
baclofen for treatment of alcohol dependance GABBR1
baclofen for treatment of alcohol dependance GABBR2
ALKS 33 for treatment of alcohol OPRD1
dependance, antidepressant
ALKS 33 for treatment of alcohol OPRK1
dependance, antidepressant
ALKS 33 for treatment of alcohol OPRM1
dependance, antidepressant
ALKS 37 motilitant OPRD1
ALKS 37 motilitant OPRK1
ALKS 37 motilitant OPRM1
ALKS 33 for treatment of alcohol OPRD1
dependance, antidepressant
ALKS 33 for treatment of alcohol OPRK1
dependance, antidepressant
ALKS 33 for treatment of alcohol OPRM1
dependance, antidepressant
buprenorphine antidepressant, analgesic, for OPRD1
treatment of opioid addiction
buprenorphine antidepressant, analgesic, for OPRK1
treatment of opioid addiction
almorexant sleep disorder treatment HCRTR1
almorexant sleep disorder treatment HCRTR2
almotriptan antimigraine agent HTR1B
almotriptan antimigraine agent HTR1D
morphine analgesic OPRD1
morphine analgesic OPRD1
morphine analgesic OPRK1
morphine analgesic OPRK1
morphine analgesic OPRM1
morphine analgesic OPRM1
naltrexone analgesic OPRD1
naltrexone analgesic OPRD1
naltrexone analgesic OPRK1
naltrexone analgesic OPRK1
naltrexone analgesic OPRM1
naltrexone analgesic OPRM1
naltrexone analgesic SIGMAR1
alogliptin antidiabetic DPP4
alosetron for treatment of irritable bowel HTR3A
syndrome
alprazolam anxiolytic, sedative, hypnotic GABRA1
alprazolam anxiolytic, sedative, hypnotic GABRA2
alprazolam anxiolytic, sedative, hypnotic GABRA3
alprazolam anxiolytic, sedative, hypnotic GABRA4
alprazolam anxiolytic, sedative, hypnotic GABRA5
alprazolam anxiolytic, sedative, hypnotic GABRA6
alprazolam anxiolytic, sedative, hypnotic GABRB1
alprazolam anxiolytic, sedative, hypnotic GABRB2
alprazolam anxiolytic, sedative, hypnotic GABRB3
alprazolam anxiolytic, sedative, hypnotic GABRD
alprazolam anxiolytic, sedative, hypnotic GABRE
alprazolam anxiolytic, sedative, hypnotic GABRG1
alprazolam anxiolytic, sedative, hypnotic GABRG2
alprazolam anxiolytic, sedative, hypnotic GABRG3
alprazolam anxiolytic, sedative, hypnotic GABRP
alprazolam anxiolytic, sedative, hypnotic GABRQ
alprazolam anxiolytic, sedative, hypnotic GABRR2
alprazolam anxiolytic, sedative, hypnotic GABRR3
alprostadil for treatment of erectile PTGER1
dysfunction, for treatment of sexual
dysfunction in women
alprostadil for treatment of erectile PTGER2
dysfunction, for treatment of sexual
dysfunction in women
alprostadil for treatment of erectile PTGER1
dysfunction, for treatment of sexual
dysfunction in women
alprostadil for treatment of erectile PTGER2
dysfunction, for treatment of sexual
dysfunction in women
alprostadil for treatment of erectile PTGER1
dysfunction, for treatment of sexual
dysfunction in women
alprostadil for treatment of erectile PTGER2
dysfunction, for treatment of sexual
dysfunction in women
altropane diagnostic agent for parkinson's SLC6A3
disease and ADHD
Alvespimycin antineoplastic agent HSP90AA1
Alvespimycin antineoplastic agent HSP90AB1
AM-101 for treatment of tinnitus GRIN1
AM-101 for treatment of tinnitus GRIN2A
AM-101 for treatment of tinnitus GRIN2B
AM-101 for treatment of tinnitus GRIN2C
AM-101 for treatment of tinnitus GRIN2D
AM-101 for treatment of tinnitus GRIN3A
AM-101 for treatment of tinnitus GRIN3B
AM-103 antiinflammatory agent ALOX5AP
AM-152 antiinflammatory agent, antifibrotic LPAR1
agent
AM-211 antiinflammatory agent, antiallergy GPR44
agent
AM-461 antiinflammatory agent PTGDR
AM-803 antiinflammatory agent ALOX5AP
AMAP102 antiinflammatory agent, DMARD HTR2B
AMAP102 antiinflammatory agent, DMARD HTR2C
AMD-070 antiviral agent, HIV CXCR4
ALS 2-0426 antidiabetic DPP4
amibegron antidepressant ADRB3
amifostine radiation-protective agent ALPPL2
amiodarone antiarrhytmic agent ADRA1A
amiodarone antiarrhytmic agent ADRB1
amiodarone antiarrhytmic agent KCNH2
amisulpride antipsychotic agent DRD2
amisulpride antipsychotic agent DRD3
amitriptyline analgesic SLC6A2
amitriptyline analgesic SLC6A4
ketamine analgesic GRIN3A
amlodipine antihypertensive agent, CACNA1C
cardiovascular agent
amlodipine antihypertensive agent, CACNA1D
cardiovascular agent
amlodipine antihypertensive agent, CACNA1S
cardiovascular agent
amlodipine antihypertensive agent, CACNA2D1
cardiovascular agent
amlodipine antihypertensive agent, CACNB2
cardiovascular agent
amonafide antineoplastic agent TOP2A
amonafide antineoplastic agent TOP2B
aliskiren antihypertensive agent REN
amlodipine antihypertensive agent CACNA1C
amlodipine antihypertensive agent CACNA1D
amlodipine antihypertensive agent CACNA1S
amlodipine antihypertensive agent CACNA2D1
amlodipine antihypertensive agent CACNB2
hydrochlorothiazide antihypertensive agent SLC12A3
AN-2728 antiinflammatory agent, antipsoriatic PDE4A
AN-2728 antiinflammatory agent, antipsoriatic PDE4B
AN-2898 antiinflammatory agent, antipsoriatic PDE4A
AN-2898 antiinflammatory agent, antipsoriatic PDE4B
ANA773 antineoplastic agent TLR7
Anacetrapib for treatment of dyslipidemia CETP
anamorelin appetite stimulating agent GHSR
anastrozole antineoplastic agent CYP19A1
anatibant for treatment of traumatic brain BDKRB2
injury
ANAVEX 2-73 for treatment of Alzheimer's disease SIGMAR1
clomifene for treatment of testosterone ESR1
deficiency
anhydrovinblastin antineoplastic agent TUBB
docetaxel antineoplastic agent TUBB1
AP1030 antiobesity agent MC1R
AP1030 antiobesity agent MC4R
oxybutynin for treatment of overactive bladder CHRM1
oxybutynin for treatment of overactive bladder CHRM2
oxybutynin for treatment of overactive bladder CHRM3
APC-100 antineoplastic agent AR
APD125 for treatment of insomnia HTR2A
APD421 antiemetic DRD2
APD668 antidiabetic GPR119
APD791 antithrombotic HTR2A
APD916 for treatment of narcolepsy HRH3
mepivacaine anestethic SCN10A
granisetron antiemetic HTR3A
apilimod antiinflammatory agent, antipsoriatic unknown
apixaban antithrombotic F10
misoprostol labor-inducing agent PTGIR
Aplindore antiparkinson agent, for treatment of DRD2
restlegs legs syndrome
apomorphine for treatment of sexual dysfunction in DRD2
women, for treatment of erectile
dysfunction, antiparkinson agent
apomorphine for treatment of sexual dysfunction in DRD3
women, for treatment of erectile
dysfunction, antiparkinson agent
apomorphine for treatment of sexual dysfunction in DRD4
women, for treatment of erectile
dysfunction, antiparkinson agent
apomorphine for treatment of sexual dysfunction in DRD2
women, for treatment of erectile
dysfunction, antiparkinson agent
apomorphine for treatment of sexual dysfunction in DRD3
women, for treatment of erectile
dysfunction, antiparkinson agent
apomorphine for treatment of sexual dysfunction in DRD4
women, for treatment of erectile
dysfunction, antiparkinson agent
apremilast antiinflammatory agent, DMARD, PDE4A
antipsoriatic
apremilast antiinflammatory agent, DMARD, PDE4B
antipsoriatic
aprepitant antiemetic TACR1
apricoxib antineoplastic agent PTGS2
AR-12 antineoplastic agent PDK1
AR-12286 for treatment of glaucoma ROCK1
AR-12286 for treatment of glaucoma ROCK2
AR-42 antineoplastic agent HDAC1
AR-42 antineoplastic agent HDAC10
AR-42 antineoplastic agent HDAC11
AR-42 antineoplastic agent HDAC2
AR-42 antineoplastic agent HDAC3
AR-42 antineoplastic agent HDAC4
AR-42 antineoplastic agent HDAC5
AR-42 antineoplastic agent HDAC6
AR-42 antineoplastic agent HDAC7A
AR-42 antineoplastic agent HDAC8
AR-42 antineoplastic agent HDAC9
AR9281 antihypertensive agent EPHX1
AR9281 antihypertensive agent EPHX2
arbaclofen symptomatic treatment for fragile X GABBR1
syndrome
arbaclofen symptomatic treatment for fragile X GABBR2
syndrome
ARC100 antineoplastic agent TUBB1
clonidine for treatment of diabetic ADRA2A
neuropathy, for treatment of
ADHD, antimucositic
clonidine for treatment of diabetic ADRA2B
neuropathy, for treatment of
ADHD, antimucositic
clonidine for treatment of diabetic ADRA2C
neuropathy, for treatment of
ADHD, antimucositic
ARD-07 for treatment of growth hormone GHR
deficiency
Argatroban anticoagulant F2
ARI-2243 antidiabetic DPP4
ARI-3037MO Vitamin B analog, for treatment for GPR109A
hyperlipidemia
ARI-3037MO Vitamin B analog, for treatment for GPR109B
hyperlipidemia
ARI-3037MO Vitamin B analog, for treatment for NNMT
hyperlipidemia
ARI-3037MO Vitamin B analog, for treatment for QPRT
hyperlipidemia
armodafinil central nervous system stimulant SLC6A3
ARN-509 antineoplastic agent AR
ARQ-197 antineoplastic agent MET
ARQ-501 antineoplastic agent TOP1
ARQ-621 antineoplastic agent KIF11
ARRY-162 antiinflammatory MAP2K1
agent, DMARD, antineoplastic agent
ARRY-162 antiinflammatory MAP2K2
agent, DMARD, antineoplastic agent
ARRY-300 antiinflammatory MAP2K1
agent, DMARD, antineoplastic agent
ARRY-300 antiinflammatory MAP2K2
agent, DMARD, antineoplastic agent
ARRY-334543 antineoplastic agent EGFR
ARRY-334543 antineoplastic agent ERBB2
ARRY-380 antineoplastic agent ERBB2
ARRY-403 antidiabetic GCK
ARRY-614 for treatment of myelodysplastic ABL1
syndrome
ARRY-614 for treatment of myelodysplastic KDR
syndrome
ARRY-614 for treatment of myelodysplastic MAPK11
syndrome
ARRY-614 for treatment of myelodysplastic MAPK12
syndrome
ARRY-614 for treatment of myelodysplastic MAPK13
syndrome
ARRY-614 for treatment of myelodysplastic MAPK14
syndrome
ARRY-614 for treatment of myelodysplastic TEK
syndrome
ARRY-797 antineoplastic agent MAPK11
ARRY-797 antineoplastic agent MAPK12
ARRY-797 antineoplastic agent MAPK13
ARRY-797 antineoplastic agent MAPK14
arsenic trioxide antineoplastic agent CCND1
arsenic trioxide antineoplastic agent IKBKB
arsenic trioxide antineoplastic agent JUN
arsenic trioxide antineoplastic agent MAPK1
arsenic trioxide antineoplastic agent MAPK3
arsenic trioxide antineoplastic agent TXNRD1
arverapamil for treatment of irritable bowel CACNA1C
syndrome
arverapamil for treatment of irritable bowel CACNA1D
syndrome
arverapamil for treatment of irritable bowel CACNA1F
syndrome
arverapamil for treatment of irritable bowel CACNA1G
syndrome
arverapamil for treatment of irritable bowel CACNA1S
syndrome
arverapamil for treatment of irritable bowel CACNB1
syndrome
arverapamil for treatment of irritable bowel CACNB2
syndrome
arverapamil for treatment of irritable bowel CACNB3
syndrome
arverapamil for treatment of irritable bowel CACNB4
syndrome
sufentanil adjuvant to anesthesia OPRM1
sufentanil adjuvant to anesthesia OPRM1
sufentanil analgesic, sedative OPRM1
triazolam analgesic, sedative GABRA1
triazolam analgesic, sedative GABRA2
triazolam analgesic, sedative GABRA3
triazolam analgesic, sedative GABRA4
triazolam analgesic, sedative GABRA5
triazolam analgesic, sedative GABRA6
triazolam analgesic, sedative GABRB1
triazolam analgesic, sedative GABRB2
triazolam analgesic, sedative GABRB3
triazolam analgesic, sedative GABRD
triazolam analgesic, sedative GABRE
triazolam analgesic, sedative GABRG1
triazolam analgesic, sedative GABRG2
triazolam analgesic, sedative GABRG3
triazolam analgesic, sedative GABRP
triazolam analgesic, sedative GABRQ
triazolam analgesic, sedative GABRR1
triazolam analgesic, sedative GABRR2
triazolam analgesic, sedative GABRR3
Arzoxifene antineoplastic agent, antiosteoporotic ESR1
agent
ASC-J9 dermatological agent AR
Asenapine antipsychotic agent ADRA1A
Asenapine antipsychotic agent ADRA2A
Asenapine antipsychotic agent ADRA2B
Asenapine antipsychotic agent ADRA2C
Asenapine antipsychotic agent DRD1
Asenapine antipsychotic agent DRD2
Asenapine antipsychotic agent DRD3
Asenapine antipsychotic agent DRD4
Asenapine antipsychotic agent HRH1
Asenapine antipsychotic agent HRH2
Asenapine antipsychotic agent HTR1A
Asenapine antipsychotic agent HTR1B
Asenapine antipsychotic agent HTR2A
Asenapine antipsychotic agent HTR2B
Asenapine antipsychotic agent HTR2C
Asenapine antipsychotic agent HTR5A
Asenapine antipsychotic agent HTR6
Asenapine antipsychotic agent HTR7
asimadoline analgesic OPRK1
ipragliflozin antidiabetic SLC5A2
AT-101 antineoplastic agent BAD
AT-101 antineoplastic agent BCL2
AT-101 antineoplastic agent MCL1
AT13387 antineoplastic agent HSP90AA1
AT13387 antineoplastic agent HSP90AB1
fentanyl analgesic OPRD1
fentanyl analgesic OPRD1
fentanyl analgesic OPRM1
fentanyl analgesic, opioid OPRM1
AT7519 antineoplastic agent CDK2
AT9283 antineoplastic agent AURKA
AT9283 antineoplastic agent AURKB
atamestane antineoplastic agent CYP19A1
toremifene antineoplastic agent ESR1
toremifene antineoplastic agent ESR2
ATHX-105 antiobesity agent HTR2C
docetaxel antineoplastic agent TUBB1
ATI-7505 Parasympathomimetic HTR4
prednisone antiinflammatory NR3C1
agent, corticosteroid
atomoxetine for treatment of ADHD SLC6A2
atorvastatin antihypecholesterolemic agent HMGCR
atrasentan antineoplastic agent EDNRA
AUS-131 for treatment of menopausal ESR2
symtpoms
AV-412 antineoplastic agent EGFR
AV-412 antineoplastic agent ERBB2
AV608 antidepressant, for treatment of TACR1
irritable bowel
syndrome, antispasmodic
tivozanib antineoplastic agent FLT1
tivozanib antineoplastic agent FLT4
tivozanib antineoplastic agent KDR
Avanafil for treatment of erectile dysfunction PDE5A
AVE-1625 antiobesity agent, for treatment for CNR1
Alzheimer's disease
phentolamine for treatment of erectile dysfunction ADRA1A
phentolamine for treatment of erectile dysfunction ADRA2A
AVL-292 antineoplastic agent BTK
AVN-101 for treatment of alzheimer's disease HTR6
AVN-211 antipsychotic agent HTR6
AVN-322 for treatment of alzheimer's disease HTR6
AVN-944 antineoplastic agent IMPDH1
AVN-944 antineoplastic agent IMPDH2
avosentan antihypertensive agent EDNRA
dextromethorphan antitussive agent GRIN3A
dextromethorphan antitussive agent SIGMAR1
axitinib antineoplastic agent FLT1
axitinib antineoplastic agent FLT4
axitinib antineoplastic agent KDR
axitinib antineoplastic agent KIT
axitinib antineoplastic agent PDGFRA
axitinib antineoplastic agent PDGFRB
AXL1717 antineoplastic agent IGF1R
prochlorperazine antimigraine agent DRD2
alprazolam anxiolytic, sedative, hypnotic GABRA1
alprazolam anxiolytic, sedative, hypnotic GABRA2
alprazolam anxiolytic, sedative, hypnotic GABRA3
alprazolam anxiolytic, sedative, hypnotic GABRA4
alprazolam anxiolytic, sedative, hypnotic GABRA5
alprazolam anxiolytic, sedative, hypnotic GABRA6
alprazolam anxiolytic, sedative, hypnotic GABRB1
alprazolam anxiolytic, sedative, hypnotic GABRB2
alprazolam anxiolytic, sedative, hypnotic GABRB3
alprazolam anxiolytic, sedative, hypnotic GABRD
alprazolam anxiolytic, sedative, hypnotic GABRE
alprazolam anxiolytic, sedative, hypnotic GABRG1
alprazolam anxiolytic, sedative, hypnotic GABRG2
alprazolam anxiolytic, sedative, hypnotic GABRG3
alprazolam anxiolytic, sedative, hypnotic GABRP
alprazolam anxiolytic, sedative, hypnotic GABRQ
alprazolam anxiolytic, sedative, hypnotic GABRR1
alprazolam anxiolytic, sedative, hypnotic GABRR2
alprazolam anxiolytic, sedative, hypnotic GABRR3
fentanyl adjuvant to anesthesia OPRD1
fentanyl adjuvant to anesthesia OPRM1
loxapine antipsychotic agent DRD2
loxapine antipsychotic agent HTR2A
zaleplon hypnotic GABRA1
zaleplon hypnotic TSPO
azacitidine antineoplastic agent DNMT1
AZD-0837 anticoagulant F2
AZD2066 analgesic, for treatment of GRM5
gastroesophageal reflux disease
AZD6244, ARRY-142886 antineoplastic agent MAP2K1
AZD6244, ARRY-142886 antineoplastic agent MAP2K2
AZD-8330 antineoplastic agent MAP2K1
AZD-8848 antiallergy agent TLR7
azelastine antiallergy agent HRH1
azelastine antiallergy agent HRH1
azilsartan antihypertensive agent AGTR1
balsalazide antiinflammatory agent ALOX5
balsalazide antiinflammatory agent PPARG
balsalazide antiinflammatory agent PTGS1
balsalazide antiinflammatory agent PTGS2
bardoxolone antineoplastic agent NFKB1
bazedoxifene antiosteoporotic agent ESR1
bazedoxifene antiosteoporotic agent ESR2
ulodesine antiinflammatory agent PNP
becatecarin antineoplastic agent TOP2A
becatecarin antineoplastic agent TOP2B
beclomethasone antiinflammatory NR3C1
agent, glucocorticoid
beclomethasone antiinflammatory NR3C1
agent, glucocorticoid
beclomethasone antiinflammatory NR3C1
agent, glucocorticoid
buprenorphine antidepressant, analgesic, for OPRK1
treatment of opioid addiction
buprenorphine antidepressant, analgesic, for OPRM1
treatment of opioid addiction
fentanyl analgesic OPRD1
fentanyl analgesic OPRM1
benazepril antihypertensive agent ACE
bepotastine antiallergy agent HRH1
beraprost antihypertensive agent PTGIR
betamethasone antiinflammatory NR3C1
agent, glucocorticoid
betamethasone antiinflammatory NR3C1
agent, glucocorticoid
betrixaban antithrombotic F10
bexarotene antineoplastic agent RXRA
bexarotene antineoplastic agent RXRB
bexarotene antineoplastic agent RXRG
BF-1 antimigraine agent HTR2B
BF-Derm 1 antiallergy agent HDC
BG-9928 for treatment of congestive heart ADORA1
failure
fluoxetine for treatment of sleep apnea SLC6A4
ondansetron for treatment of sleep apnea HTR3A
BGC20-1531 antimigraine agent PTGER4
BGG-492 anticonvulsant, antimigraine agent GRIA1
BGG-492 anticonvulsant, antimigraine agent GRIA2
BGG-492 anticonvulsant, antimigraine agent GRIA3
BGG-492 anticonvulsant, antimigraine agent GRIA4
progesterone neuroprotectant for stroke victims ESR1
progesterone neuroprotectant for stroke victims NR3C2
progesterone neuroprotectant for stroke victims PGR
BI-10773 antidiabetic SLC5A2
olodaterol bronchodilator ADRB2
Nintedanib antineoplastic agent FGFR1
Nintedanib antineoplastic agent FGFR2
Nintedanib antineoplastic agent FGFR3
Nintedanib antineoplastic agent FLT1
Nintedanib antineoplastic agent FLT4
Nintedanib antineoplastic agent KDR
Nintedanib antineoplastic agent PDGFRA
Nintedanib antineoplastic agent PDGFRB
Bicalutamide antineoplastic agent AR
bifeprunox antipsychotic agent, antiparkinson DRD2
agent
bifeprunox antipsychotic agent, antiparkinson DRD3
agent
bifeprunox antipsychotic agent, antiparkinson HTR1A
agent
bifeprunox antipsychotic agent, antiparkinson HTR2A
agent
bifeprunox antipsychotic agent, antiparkinson HTR2C
agent
bifeprunox antipsychotic agent, antiparkinson HTR7
agent
BIM23A760 antineoplastic agent, treatment for DRD2
acromegaly
BIM23A760 antineoplastic agent, treatment for SSTR2
acromegaly
BIM23A760 antineoplastic agent, treatment for SSTR5
acromegaly
bimatoprost antiglaucomic agent PTGER1
bimatoprost antiglaucomic agent PTGER3
bimatoprost antiglaucomic agent PTGFR
bimoclomol for treatment of diabetic neuropathy HSF1
bimosiamose antiinflammatory agent, antipsoriatic SELE
bimosiamose antiinflammatory agent, antipsoriatic SELL
bimosiamose antiinflammatory agent, antipsoriatic SELP
docetaxel antineoplastic agent BCL2
docetaxel antineoplastic agent TUBB1
binodenoson diagnostic agent ADORA2A
estradiol hormone replacement, treatment for ESR1
menopause
estradiol hormone replacement, treatment for ESR2
menopause
testosterone hormone replacement AR
dapagliflozin antidiabetic SLC5A2
BMS-582949 antiinflammatory MAPK11
agent, DMARD, antipsoriatic
BMS-582949 antiinflammatory MAPK12
agent, DMARD, antipsoriatic
BMS-582949 antiinflammatory MAPK13
agent, DMARD, antipsoriatic
BMS-582949 antiinflammatory MAPK14
agent, DMARD, antipsoriatic
BMS-299897 for treatment of alzheimer's disease APH1A
BMS-299897 for treatment of alzheimer's disease APH1B
BMS-299897 for treatment of alzheimer's disease NCSTN
BMS-299897 for treatment of alzheimer's disease PSEN1
BMS-299897 for treatment of alzheimer's disease PSEN2
BMS-299897 for treatment of alzheimer's disease PSENEN
BMS-708163 for treatment of alzheimer's disease APH1A
BMS-708163 for treatment of alzheimer's disease APH1B
BMS-708163 for treatment of alzheimer's disease NCSTN
BMS-708163 for treatment of alzheimer's disease PSEN1
BMS-708163 for treatment of alzheimer's disease PSEN2
BMS-708163 for treatment of alzheimer's disease PSENEN
BMS-754807 antineoplastic agent IGF1R
BMS-863233 antineoplastic agent CDC7
calcitonin antiosteoporotic agent CALCR
NCX116 for treatment of glaucoma PTGFR
bosutinib antineoplastic agent ABL1
bosutinib antineoplastic agent SRC
brimonidine for treatment of glaucoma ADRA2A
brimonidine for treatment of glaucoma ADRA2A
timolol for treatment of glaucoma ADRB1
timolol for treatment of glaucoma ADRB2
Brivaracetam anticonvulsant SV2A
bromfenac opthalmological agent, NSAID PTGS1
bromfenac opthalmological agent, NSAID PTGS2
bromocriptine antidiabetic DRD2
bromocriptine antidiabetic DRD3
Bryostatin for treatment of alzheimer's disease PRKCA
Bryostatin for treatment of alzheimer's disease PRKCB
Bryostatin for treatment of alzheimer's disease PRKCD
Bryostatin for treatment of alzheimer's disease PRKCE
Bryostatin for treatment of alzheimer's disease PRKCG
Bryostatin for treatment of alzheimer's disease PRKCH
Bryostatin for treatment of alzheimer's disease PRKCQ
Bryostatin for treatment of alzheimer's disease PRKD1
Bryostatin for treatment of alzheimer's disease PRKD2
Bryostatin for treatment of alzheimer's disease PRKD3
Bryostatin-1 antineoplastic agent PRKCA
Bryostatin-1 antineoplastic agent PRKCB
Bryostatin-1 antineoplastic agent PRKCD
Bryostatin-1 antineoplastic agent PRKCE
Bryostatin-1 antineoplastic agent PRKCG
Bryostatin-1 antineoplastic agent PRKCH
Bryostatin-1 antineoplastic agent PRKCQ
Bryostatin-1 antineoplastic agent PRKD1
Bryostatin-1 antineoplastic agent PRKD2
Bryostatin-1 antineoplastic agent PRKD3
fentanyl analgesic OPRD1
fentanyl analgesic OPRM1
prochlorperazine antiemetic DRD2
bucindolol for treatment of heart failure ADRB1
bucindolol for treatment of heart failure ADRB2
budesonide antiinflammatory NR3C1
agent, glucocorticoid
Formoterol bronchodilator ADRB2
budesonide antiinflammatory NR3C1
agent, glucocorticoid
budesonide antiinflammatory NR3C1
agent, glucocorticoid
budesonide antiinflammatory NR3C1
agent, glucocorticoid
budesonide antiinflammatory NR3C1
agent, glucocorticoid
budesonide antiinflammatory NR3C1
agent, glucocorticoid
budesonide antiinflammatory NR3C1
agent, glucocorticoid
budiodarone antiarrhytmic agent ADRB1
budiodarone antiarrhytmic agent CACNA2D2
budiodarone antiarrhytmic agent KCNH2
buprenorphine antidepressant, analgesic, for OPRK1
treatment of opioid addiction
buprenorphine antidepressant, analgesic, for OPRM1
treatment of opioid addiction
naloxone analgesic OPRK1
naloxone analgesic OPRM1
buprenorphine antidepressant, analgesic, for OPRK1
treatment of opioid addiction
buprenorphine antidepressant, analgesic, for OPRM1
treatment of opioid addiction
naloxone for treatment of opioid addiction OPRK1
naloxone for treatment of opioid addiction OPRM1
buprenorphine antidepressant, analgesic, for OPRK1
treatment of opioid addiction
buprenorphine antidepressant, analgesic, for OPRM1
treatment of opioid addiction
buprenorphine antidepressant, analgesic, for OPRK1
treatment of opioid addiction
buprenorphine antidepressant, analgesic, for OPRM1
treatment of opioid addiction
buprenorphine antidepressant, analgesic, for OPRK1
treatment of opioid addiction
buprenorphine antidepressant, analgesic, for OPRM1
treatment of opioid addiction
bupropion antidepressant, appetite SLC6A2
suppressant, smoking-cessation agent
bupropion antidepressant, appetite SLC6A3
suppressant, smoking-cessation agent
BVT.115959 analgesic ADORA2A
BVT.28949 for treatment of glaucoma HTR2A
amphetamine for treatment of cognitive CARTPT
dysfunction, for treatment of ADHD
amphetamine for treatment of cognitive SLC18A2
dysfunction, for treatment of ADHD
amphetamine for treatment of cognitive SLC6A3
dysfunction, for treatment of ADHD
amphetamine for treatment of cognitive TAAR1
dysfunction, for treatment of ADHD
C-1311 antineoplastic agent TOP1
C-1311 antineoplastic agent TOP2A
cabazitaxel antineoplastic agent TUBA4A
cabazitaxel antineoplastic agent TUBB1
amlodipine antihypertensive agent, CACNA1C
cardiovascular agent
amlodipine antihypertensive agent, CACNA1D
cardiovascular agent
amlodipine antihypertensive agent, CACNA1S
cardiovascular agent
amlodipine antihypertensive agent, CACNA2D1
cardiovascular agent
amlodipine antihypertensive agent, CACNB2
cardiovascular agent
atorvastatin anticholesterolaemic agent HMGCR
CAL-101 antineoplastic agent PIK3CD
betamethasone antiinflammatory NR3C1
agent, glucocorticoid
calcipotriene antipsoriatic agent VDR
calcitriol antipsoriatic agent VDR
buprenorphine antidepressant, analgesic, for OPRK1
treatment of opioid addiction
buprenorphine antidepressant, analgesic, for OPRM1
treatment of opioid addiction
Canagliflozin antidiabetic SLC5A2
candesartan antihypertensive agent AGTR1
cangrelor antithrombotic P2RY12
PRS-211375 analgesic CNR2
CAP7.1 antineoplastic agent TOP2A
Caprospinol for treatment of alzheimer's disease APP
Carfilzomib antineoplastic agent PSMB1
Carfilzomib antineoplastic agent PSMB2
Carfilzomib antineoplastic agent PSMB5
cariprazine antipsychotic agent DRD2
cariprazine antipsychotic agent DRD3
carvedilol for treatment of congestive heart ADRA1A
failure
carvedilol cardiovascular agent ADRB1
carvedilol cardiovascular agent ADRB2
Casopitant antiemetic TACR1
dronabinol analgesic CNR1
dronabinol analgesic CNR2
CB-03-01 dermatological agent AR
caricotamide antineoplastic agent NQO2
tretazicar antineoplastic agent DNA
abiraterone antineoplastic agent CYP17A1
JNK-401 antineoplastic agent MAPK10
JNK-401 antineoplastic agent MAPK8
JNK-401 antineoplastic agent MAPK9
CCX025 antiinflammatory agent CCR9
CCX140 antiinflammatory agent, antidiabetic CCR2
CCX168 antiinflammatory agent, for treatment C5AR1
for autoimmune disease
CCX282 antiinflammatory agent, for treatment CCR9
of Chron's disease, for treatment of
ulceraite colitis
CCX354 antiinflammatory agent, DMARD CCR1
CCX832 antiinflammatory agent, for treatment CMKLR1
for autoimmune disease
fenofibrate anticholesterolaemic agent PPARA
azelastine antiallergy agent HRH1
budesonide antiinflammatory NR3C1
agent, glucocorticoid
cediranib antineoplastic agent FLT1
cediranib antineoplastic agent FLT4
cediranib antineoplastic agent KDR
celecoxib NSAID PTGS2
mycophenolate mofetil immunosuppressant IMPDH1
mycophenolate mofetil immunosuppressant IMPDH2
synthetic conjugated estrogens for treatment of postmenopausal ESR1
symptoms
synthetic conjugated estrogens for treatment of postmenopausal ESR2
symptoms
histamine cytorprotective agent during cancer HRH2
treatment
CER-002 cardiovascular agent PPARD
acetylsalicylic acid NSAID PTGS1
acetylsalicylic acid NSAID PTGS2
niacin antidyslipidaemic agent GPR109A
niacin antidyslipidaemic agent GPR109B
niacin antidyslipidaemic agent NNMT
niacin antidyslipidaemic agent QPRT
diclofenac NSAID PTGS1
diclofenac NSAID PTGS2
cetilistat antiobesity agent PNLIP
cetirizine antiallergy agent HRH1
CF-101 antiinflammatory agent, DMARD ADORA3
CF-102 antineoplastic agent ADORA3
CG100649 NSAID CA1
CG100649 NSAID PTGS2
clopidogrel antiplatelet agent P2RY12
omeprazol antiulcer agent ATP4A
CH-1504 antiinflammatory agent, DMARD DHFR
CHF 4227 antiosteoporotic agent ESR1
CHF 4227 antiosteoporotic agent ESR2
beclomethasone antiinflammatory NR3C1
agent, glucocorticoid
formoterol antiasthmatic agent ADRB2
chidamide antineoplastic agent HDAC1
chidamide antineoplastic agent HDAC10
chidamide antineoplastic agent HDAC2
chidamide antineoplastic agent HDAC3
CHIR-265 antineoplastic agent BRAF
CHIR-265 antineoplastic agent KDR
CHIR-265 antineoplastic agent RAF1
cyclosporine immunosuppressant CAMLG
cyclosporine immunosuppressant PPP3R2
tadalafil for treatment of erectile dysfunction PDE5A
cilansetron for treatment of irritable bowel HTR3A
syndrome
cimicoxib NSAID PTGS2
isotretinoin for treatment of acne RARA
escitalopram antidepressant SLC6A4
tiramsetiv for treatment of skeletal muscle TNNC1
disorders associated with aging and
neuro-degenerative disorders.
tiramsetiv for treatment of skeletal muscle TNNC2
disorders associated with aging and
neuro-degenerative disorders.
tiramsetiv for treatment of skeletal muscle TNNI1
disorders associated with aging and
neuro-degenerative disorders.
tiramsetiv for treatment of skeletal muscle TNNI2
disorders associated with aging and
neuro-degenerative disorders.
tiramsetiv for treatment of skeletal muscle TNNT1
disorders associated with aging and
neuro-degenerative disorders.
tiramsetiv for treatment of skeletal muscle TNNT2
disorders associated with aging and
neuro-degenerative disorders.
clazosentan for treatment and prevention of EDNRA
vasospasm
clevidipine antihypertensive agent CACNA1C
clevidipine antihypertensive agent CACNA1D
clevidipine antihypertensive agent CACNA1F
clevidipine antihypertensive agent CACNA1S
clobazam anxiolytic, anticonvulsant GABRA1
clobazam anxiolytic, anticonvulsant GABRA2
clobazam anxiolytic, anticonvulsant GABRA3
clobazam anxiolytic, anticonvulsant GABRA4
clobazam anxiolytic, anticonvulsant GABRA5
clobazam anxiolytic, anticonvulsant GABRA6
clobazam anxiolytic, anticonvulsant GABRB1
clobazam anxiolytic, anticonvulsant GABRB2
clobazam anxiolytic, anticonvulsant GABRB3
clobazam anxiolytic, anticonvulsant GABRD
clobazam anxiolytic, anticonvulsant GABRE
clobazam anxiolytic, anticonvulsant GABRG1
clobazam anxiolytic, anticonvulsant GABRG2
clobazam anxiolytic, anticonvulsant GABRG3
clobazam anxiolytic, anticonvulsant GABRP
clobazam anxiolytic, anticonvulsant GABRQ
clobazam anxiolytic, anticonvulsant GABRR1
clobazam anxiolytic, anticonvulsant GABRR2
clobazam anxiolytic, anticonvulsant GABRR3
clobetasol antiinflammatory NR3C1
agent, corticosteroid
clodronate antineoplastic agent SLC25A4
clodronate antineoplastic agent SLC25A5
clodronate antineoplastic agent SLC25A6
Clofarabine antineoplastic agent POLA1
Clofarabine antineoplastic agent RRM1
clonidine for treatment of diabetic ADRA2A
neuropathy, for treatment of
ADHD, antimucositic
clonidine for treatment of diabetic ADRA2B
neuropathy, for treatment of
ADHD, antimucositic
clonidine for treatment of diabetic ADRA2C
neuropathy, for treatment of
ADHD, antimucositic
clonidine for treatment of diabetic ADRA2A
neuropathy, for treatment of
ADHD, antimucositic
clonidine for treatment of diabetic ADRA2B
neuropathy, for treatment of
ADHD, antimucositic
clonidine for treatment of diabetic ADRA2C
neuropathy, for treatment of
ADHD, antimucositic
CLX-0921 antidiabetic PPARG
CM2489 antiinflammatory agent, antipsoriatic ORA1
CNDO101 antineoplastic agent TOP2A
CNF1010 antineoplastic agent HSP90AA1
CNF1010 antineoplastic agent HSP90AB1
CNS-5161 analgesic GRIN1
CNS-5161 analgesic GRIN2A
CNS-5161 analgesic GRIN2B
CNS-5161 analgesic GRIN2C
CNS-5161 analgesic GRIN2D
CNS-5161 analgesic GRIN3A
CNS-5161 analgesic GRIN3B
CNS-7056 sedative GABRA2
CNS-7056 sedative GABRA3
CNS-7056 sedative GABRA5
CNS-7056 sedative GABRA6
CNS-7056 sedative GABRB1
CNS-7056 sedative GABRB1
CNS-7056 sedative GABRB2
CNS-7056 sedative GABRB2
CNS-7056 sedative GABRB3
CNS-7056 sedative GABRD
CNS-7056 sedative GABRD
CNS-7056 sedative GABRE
CNS-7056 sedative GABRG1
CNS-7056 sedative GABRG2
CNS-7056 sedative GABRG3
CNS-7056 sedative GABRG3
CNS-7056 sedative GABRP
CNS-7056 sedative GABRQ
CNS-7056 sedative GABRR2
CNV2197944 analgesic CACNA1B
oxycodone analgesic OPRD1
oxycodone analgesic OPRK1
oxycodone analgesic OPRM1
oxycodone analgesic OPRD1
oxycodone analgesic OPRK1
oxycodone analgesic OPRM1
COL-3 antineoplastic agent MMP2
COL-3 antineoplastic agent MMP9
colchicine for treatment of gout TUBB
bupivacaine local anestethic, analgesic, neuralgia SCN10A
conivaptan for treatment of hyponatremia AVPR1A
conivaptan for treatment of hyponatremia AVPR2
estrogen for symptomatic treatment of ESR1
menopausal symptoms
estrogen for symptomatic treatment of ESR2
menopausal symptoms
progesterone for symptomatic treatment of ESR1
menopausal symptoms
progesterone for symptomatic treatment of NR3C2
menopausal symptoms
progesterone for symptomatic treatment of PGR
menopausal symptoms
ethinyl estradiol contraceptive ESR1
gestodene contraceptive PGR
bupropion antidepressant, appetite SLC6A2
suppressant, smoking-cessation agent
bupropion antidepressant, appetite SLC6A3
suppressant, smoking-cessation agent
naltrexone appetite suppressant OPRD1
naltrexone appetite suppressant OPRK1
naltrexone appetite suppressant OPRM1
fomepizole for treatment of ethanol intolerance ADH1A
fomepizole for treatment of ethanol intolerance ADH1B
fomepizole for treatment of ethanol intolerance ADH1C
cordycepin antineoplastic agent DNTT
CORT 108297 for prevention of weight gain during NR3C1
antipsychotic treatment
CP-4126 antineoplastic agent DNA
CP-609,754 antineoplastic agent FNTA
CP-609,754 antineoplastic agent FNTB
CPG 10101 immunostimulant TLR9
CPG 52364 antiinflammatory agent TLR7
CPG 52364 antiinflammatory agent TLR8
CPG 52364 antiinflammatory agent TLR9
CPI-613 antineoplastic agent PDHA1
CPI-613 antineoplastic agent PDHA2
CPI-613 antineoplastic agent PDHB
CPI-613 antineoplastic agent PDK1
CPI-613 antineoplastic agent PDK2
CPI-613 antineoplastic agent PDK3
CPI-613 antineoplastic agent PDK4
semapimod antiinflammatory agent, for treatment MAPK11
of Chron's disease
semapimod antiinflammatory agent, for treatment MAPK12
of Chron's disease
semapimod antiinflammatory agent, for treatment MAPK13
of Chron's disease
semapimod antiinflammatory agent, for treatment MAPK14
of Chron's disease
floxuridine antineoplastic agent TYMS
irinotecan antineoplastic agent TOP1
irinotecan antineoplastic agent TOP1MT
cytarabine antineoplastic agent POLB
daunorubicin antineoplastic agent TOP2A
daunorubicin antineoplastic agent TOP2B
CR665 analgesic OPRK1
CR845 analgesic OPRK1
pravastatin antihypecholesterolemic agent HMGCR
rosuvastatin antihypecholesterolemic agent HMGCR
561679 antidepressant CRHR1
crizotinib antineoplastic agent ALK
crizotinib antineoplastic agent MET
CRTH2 receptor antagonist antiallergy agent GPR44
prednisolone antiinflammatory NR3C1
agent, corticosteroid
dipyridamole anticoagulant ADA
dipyridamole anticoagulant PDE10A
dipyridamole anticoagulant PDE4A
dipyridamole anticoagulant PDE5A
amoxapine antidepressant SLC6A2
amoxapine antidepressant SLC6A4
prednisolone antiinflammatory NR3C1
agent, corticosteroid
paroxetine antidepressant SLC6A4
prednisolone antiinflammatory NR3C1
agent, corticosteroid
amoxapine antidepressant SLC6A2
amoxapine antidepressant SLC6A4
dipyridamole antithrombotic ADA
dipyridamole antithrombotic PDE10A
dipyridamole antithrombotic PDE4A
dipyridamole antithrombotic PDE5A
budesonide antiinflammatory NR3C1
agent, glucocorticoid
nortriptyline antiasthmatic agent SLC6A2
nortriptyline antiasthmatic agent SLC6A4
mometasone antiinflammatory NR3C1
agent, glucocorticoid
nortriptyline antidepressant SLC6A2
nortriptyline antidepressant SLC6A4
bezafibrate antidiabetic PPARA
diflunisal antidiabetic PTGS1
diflunisal antidiabetic PTGS2
CS-3030 anticoagulant F10
CS-7017 antineoplastic agent PPARG
amlodipine antihypertensive agent CACNA1C
amlodipine antihypertensive agent CACNA1D
amlodipine antihypertensive agent CACNA1S
amlodipine antihypertensive agent CACNA2D1
amlodipine antihypertensive agent CACNB2
olmesartan antihypertensive agent AGTR1
CTA018 antiinflammatory agent, antipsoriatic CYP24A1
CTS-21166 for treatment of Alzheimer's disease BACE1
CUDC-101 antineoplastic agent EGFR
CUDC-101 antineoplastic agent ERBB2
CUDC-101 antineoplastic agent HDAC1
CUDC-101 antineoplastic agent HDAC10
CUDC-101 antineoplastic agent HDAC11
CUDC-101 antineoplastic agent HDAC2
CUDC-101 antineoplastic agent HDAC3
CUDC-101 antineoplastic agent HDAC4
CUDC-101 antineoplastic agent HDAC5
CUDC-101 antineoplastic agent HDAC6
CUDC-101 antineoplastic agent HDAC7
CUDC-101 antineoplastic agent HDAC8
CUDC-101 antineoplastic agent HDAC9
CVT-3619 antihyperlipidemic agent ADORA1
CVT-6883 antiasthmatic agent ADORA2B
CX157 antidepressant MAOA
CX1632/S 47445 for treatment of Alzheimer's disease GRIA1
CX1632/S 47445 for treatment of Alzheimer's disease GRIA2
CX1632/S 47445 for treatment of Alzheimer's disease GRIA3
CX1632/S 47445 for treatment of Alzheimer's disease GRIA4
CX-4945 antineoplastic agent CSNK2A1
CX717 for treatment of Alzheimer's disease GRIA1
CX717 for treatment of Alzheimer's disease GRIA2
CX717 for treatment of Alzheimer's disease GRIA3
CX717 for treatment of Alzheimer's disease GRIA4
CXB909 for treatment of chemotherapy- LNGFR
induced peripheral neuropathy
CXB909 for treatment of chemotherapy- NTRK1
induced peripheral neuropathy
CYC116 antineoplastic agent AURKA
CYC116 antineoplastic agent AURKB
CYC116 antineoplastic agent KDR
cyclosporine immunosuppressant CAMLG
cyclosporine immunosuppressant PPP3R2
duloxetine antidepressant SLC6A2
duloxetine antidepressant SLC6A4
cysteamine for treatment of corneal cystine cystine
accumulation
cytarabine antineoplastic agent POLB
D3263 antineoplastic agent TRPM8
Dabigatran anticoagulant F2
decitabine antineoplastic agent DNMT1
dapoxetine for treatment of premature SLC6A4
ejacul*tion
darapladib antiinflammatory agent, DMARD PLA2G7
darifenacin for treatment of overactive bladder CHRM3
darusentan antihypertensive agent EDNRA
dasatinib antineoplastic agent ABL1
dasatinib antineoplastic agent ABL2
dasatinib antineoplastic agent EPHA2
dasatinib antineoplastic agent FYN
dasatinib antineoplastic agent KIT
dasatinib antineoplastic agent LCK
dasatinib antineoplastic agent PDGFRB
dasatinib antineoplastic agent SRC
dasatinib antineoplastic agent STAT5B
dasatinib antineoplastic agent YES1
methylphenidate for treatment of ADHD SLC6A3
DB-959 antidiabetic PPARD
DB-959 antidiabetic PPARG
diazoxide choline antidyslipidaemic agent ABCC8
DDP225 for treatment of irritable bowel HTR3A
syndrome
DDP225 for treatment of irritable bowel HTR3B
syndrome
DDP225 for treatment of irritable bowel HTR3C
syndrome
DDP225 for treatment of irritable bowel HTR3D
syndrome
DDP225 for treatment of irritable bowel HTR3E
syndrome
DDP225 for treatment of irritable bowel SLC6A2
syndrome
Debio 0932 antineoplastic agent HSP90AA1
Debio 0932 antineoplastic agent HSP90AB1
DEBIO-9902 SR for treatment of Alzheimer's disease ACHE
Degarelix antineoplastic agent GNRHR
Degarelix antineoplastic agent GNRHR2
denufosol for treatment of cystic fibrosis P2RY2
deoxynojirimycin for treatment of Pompe disease GAA
bupivacaine local anestethic, analgesic, neuralgia SCN10A
gabapentin for treatment of neuropathic pain CACNA1B
gabapentin for treatment of neuropathic pain CACNA2D1
gabapentin for treatment of neuropathic pain CACNA2D2
romidepsin antineoplastic agent HDAC1
romidepsin antineoplastic agent HDAC10
romidepsin antineoplastic agent HDAC11
romidepsin antineoplastic agent HDAC2
romidepsin antineoplastic agent HDAC3
romidepsin antineoplastic agent HDAC4
romidepsin antineoplastic agent HDAC5
romidepsin antineoplastic agent HDAC6
romidepsin antineoplastic agent HDAC7A
romidepsin antineoplastic agent HDAC8
romidepsin antineoplastic agent HDAC9
dersalazine antiinflammatory agent, for treatment PTGS1
of ulcerative colitis
dersalazine antiinflammatory agent, for treatment PTGS2
of ulcerative colitis
dersalazine antiinflammatory agent, for treatment TNF
of ulcerative colitis
desloratadine antiallergy agent HRH1
desonide antiinflammatory NR3C1
agent, corticosteroid
dexamethasone antiinflammatory NR3C1
agent, glucocorticoid, for treatment of
Meniere's disease
Dexanabinol neuroprotectant GRIN1
Dexanabinol neuroprotectant GRIN2A
Dexanabinol neuroprotectant GRIN2B
Dexanabinol neuroprotectant GRIN2D
Dexanabinol neuroprotectant GRIN3A
Dexanabinol neuroprotectant GRIN3B
dexlipotam for treatment of diabetic neuropathy PDHB
dexloxiglumide motilitant CCKAR
dexpramipexole for treatment of amyotrophic lateral DRD2
sclerosis (ALS)
dexpramipexole for treatment of amyotrophic lateral DRD3
sclerosis (ALS)
dexpramipexole for treatment of amyotrophic lateral DRD4
sclerosis (ALS)
DG031 antiinflammatory agent, myocardial ALOX5AP
infarction prophylaxis
DG041 Platelet Aggregation Inhibitor PTGER3
DG051 antiinflammatory agent, myocardial LTA4H
infarction prophylaxis
DG071 for treatment of alzheimer's disease PDE4A
DG071 for treatment of alzheimer's disease PDE4B
DG3173 hormone replacement SSTR1
DG3173 hormone replacement SSTR2
DG3173 hormone replacement SSTR4
DG3173 hormone replacement SSTR5
diazepam anticonvulsant GABRA1
diazepam anticonvulsant GABRA2
diazepam anticonvulsant GABRA3
diazepam anticonvulsant GABRA5
diazepam anticonvulsant GABRB1
diazepam anticonvulsant GABRB2
diazepam anticonvulsant GABRB3
diazepam anticonvulsant GABRD
diazepam anticonvulsant GABRE
diazepam anticonvulsant GABRG1
diazepam anticonvulsant GABRG2
diazepam anticonvulsant GABRG3
diazepam anticonvulsant GABRP
diazepam anticonvulsant GABRQ
diazepam anticonvulsant GABRR1
diazepam anticonvulsant GABRR2
diazepam anticonvulsant GABRR3
diclofenac analgesic PTGS1
diclofenac analgesic PTGS2
Diclofenac analgesic PTGS1
Diclofenac analgesic PTGS2
Diclofenac analgesic PTGS1
Diclofenac analgesic PTGS2
Diclofenac NSAID PTGS1
Diclofenac NSAID PTGS2
Diclofenac for treatment of glaucoma PTGS1
Diclofenac for treatment of glaucoma PTGS2
difluprednate antiinflammatory NR3C1
agent, corticosteroid
diltiazem antihypertensive agent CACNG1
latrepirdine neuroprotectant ACHE
latrepirdine neuroprotectant GRIN1
latrepirdine neuroprotectant GRIN2A
latrepirdine neuroprotectant GRIN2B
latrepirdine neuroprotectant GRIN2C
latrepirdine neuroprotectant GRIN2D
latrepirdine neuroprotectant GRIN3A
latrepirdine neuroprotectant GRIN3B
dimiracetam nootropic GRIN1
dimiracetam nootropic GRIN2A
dimiracetam nootropic GRIN2B
dimiracetam nootropic GRIN2C
dimiracetam nootropic GRIN2D
DIO-902 antidiabetic ERG11
diquafosol opthalmological agent P2RY2
carbidopa antiparkinson agent DDC
levodopa antiparkinson agent DRD1
levodopa antiparkinson agent DRD2
omeprazole antiulcer agent ATP4A
betanechol antidiabetic CHRM2
calcitriol antineoplastic agent VDR
Docetaxel antineoplastic agent BCL2
Docetaxel antineoplastic agent TBB1
dolasetron antiemetic HTR3A
dolasetron antiemetic HTR3B
dolasetron antiemetic HTR3C
dolasetron antiemetic HTR3D
dolasetron antiemetic HTR3E
donepezil for treatment of alzheimer's disease ACHE
beclomethasone dipropionate antiinflammatory NR3C1
agent, glucocorticoid
DOV 102,677 antidepressant SLC6A2
DOV 102,677 antidepressant SLC6A3
DOV 102,677 antidepressant SLC6A4
DOV 216,303 antidepressant SLC6A2
DOV 216,303 antidepressant SLC6A3
DOV 216,303 antidepressant SLC6A4
DOV 21947 antidepressant SLC6A2
DOV 21947 antidepressant SLC6A3
DOV 21947 antidepressant SLC6A4
dovitinib antineoplastic agent FGFR1
dovitinib antineoplastic agent FGFR2
dovitinib antineoplastic agent FGFR3
dovitinib antineoplastic agent FLT1
dovitinib antineoplastic agent FLT1
dovitinib antineoplastic agent FLT1
dovitinib antineoplastic agent FLT4
dovitinib antineoplastic agent KDR
dovitinib antineoplastic agent PDGFRB
doxepin antimigraine agent SLC6A2
doxepin antimigraine agent SLC6A4
doxercalciferol for treatment of secondary VDR
hyperparathyroidism
doxorubicin antineoplastic agent TOP2A
doxorubicin antineoplastic agent TOP2A
doxorubicin antineoplastic agent TOP2A
doxorubicin antineoplastic agent TOP2A
DP-VPA anticonvulsant ABAT
DRF 10945 antidyslipidaemic agent PPARA
dronabinol appetite stimulant CNR1
drospirenone hormone replacement PGR
estradiol hormone replacement ESR1
estradiol hormone replacement ESR2
DSC-103 antiosteoporotic agent VDR
DTS-201 antineoplastic agent TOP2A
bupivacaine local anestethic, analgesic, neuralgia SCN10A
bupivacaine local anestethic, analgesic, neuralgia SCN10A
sildenafil for treatment of erectile dysfunction PDE5A
dutasteride for treatment of benign prostate SRD5A1
hyperplasia
dutasteride for treatment of benign prostate SRD5A2
hyperplasia
tamsulosin for treatment of benign prostatic ADRA1A
hyperplasia
dutasteride for treatment of benign prostate SRD5A1
hyperplasia
dutogliptin antidiabetic DPP4
azelastine antiallergy agent HRH1
fluticasone antiinflammatory NR3C1
agent, glucocorticoid
perampanel anticonvulsant GRIA1
perampanel anticonvulsant GRIA2
perampanel anticonvulsant GRIA3
perampanel anticonvulsant GRIA4
E2012 for treatment of Alzheimer's disease PSEN1
lenvatinib antineoplastic agent FGFR1
lenvatinib antineoplastic agent FLT1
lenvatinib antineoplastic agent FLT4
lenvatinib antineoplastic agent KDR
lenvatinib antineoplastic agent KIT
lenvatinib antineoplastic agent PDGFRA
lenvatinib antineoplastic agent PDGFRB
ecabet antiulcer agent PGA3
ecabet antiulcer agent PGC
ecopipam for treatment of tourettes DRD1
syndrome, for treatment of
pathological gambling
edoxaban antithrombotic F10
venlafaxine antidepressant SLC6A2
venlafaxine antidepressant SLC6A4
eflornithine for treatment of unwanted facial hair ODC1
in women
dexamethasone antiinflammatory NR3C1
agent, glucocorticoid, for treatment of
Meniere's disease
Etazolate for treatment of alzheimer's disease GABRA2
Etazolate for treatment of alzheimer's disease GABRA3
Etazolate for treatment of alzheimer's disease GABRB1
Etazolate for treatment of alzheimer's disease GABRB2
Etazolate for treatment of alzheimer's disease GABRE
Etazolate for treatment of alzheimer's disease GABRG1
Etazolate for treatment of alzheimer's disease PDE4A
Etazolate for treatment of alzheimer's disease PDE4B
Etazolate for treatment of alzheimer's disease PDE4C
Etazolate for treatment of alzheimer's disease PDE4D
ronomilast antiinflammatory agent PDE4A
ronomilast antiinflammatory agent PDE4B
ED-71 antiosteoporotic agent VDR
oxycodone analgesic OPRD1
oxycodone analgesic OPRK1
oxycodone analgesic OPRM1
eliglustat for treatment of Gaucher's disease UGCG
elinogrel antiplatelet agent P2RY12
Elocalcitol for treatment of benign prostatic VDR
hyperplasia
bupropion antidepressant, appetite SLC6A2
suppressant, smoking-cessation agent
bupropion antidepressant, appetite SLC6A3
suppressant, smoking-cessation agent
zonisamide appetite suppressant CACNA1G
zonisamide appetite suppressant CACNA1H
zonisamide appetite suppressant CACNA1I
zonisamide appetite suppressant SCN11A
zonisamide appetite suppressant SCN1A
zonisamide appetite suppressant SCN1B
zonisamide appetite suppressant SCN2A
zonisamide appetite suppressant SCN2B
zonisamide appetite suppressant SCN3A
zonisamide appetite suppressant SCN3B
zonisamide appetite suppressant SCN4A
zonisamide appetite suppressant SCN4B
zonisamide appetite suppressant SCN5A
zonisamide appetite suppressant SCN9A
enalapril antihypertensive agent ACE
felodipine antihypertensive agent CACNA1C
felodipine antihypertensive agent CACNA1D
felodipine antihypertensive agent CACNA1S
felodipine antihypertensive agent CACNA2D1
felodipine antihypertensive agent CACNANB2
pacl*taxel antineoplastic agent BCL2
pacl*taxel antineoplastic agent TUBB1
eniluracil antineoplastic agent DPYD
ENMD-1198 antineoplastic agent HIF1A
ENMD-2076 antineoplastic agent ABL1
ENMD-2076 antineoplastic agent AURKA
ENMD-2076 antineoplastic agent BLK
ENMD-2076 antineoplastic agent CSF1R
ENMD-2076 antineoplastic agent FGFR1
ENMD-2076 antineoplastic agent FGFR2
ENMD-2076 antineoplastic agent FLT3
ENMD-2076 antineoplastic agent FLT4
ENMD-2076 antineoplastic agent FYN
ENMD-2076 antineoplastic agent JAK2
ENMD-2076 antineoplastic agent KDR
ENMD-2076 antineoplastic agent KIT
ENMD-2076 antineoplastic agent LCK
ENMD-2076 antineoplastic agent NTRK1
ENMD-2076 antineoplastic agent PDGFRA
ENMD-2076 antineoplastic agent PTK2
ENMD-2076 antineoplastic agent RET
ENMD-2076 antineoplastic agent SRC
ENMD-2076 antineoplastic agent YES1
entacapone antiparkinson agent COMT
carbidopa antiparkinson agent DDC
entacapone antiparkinson agent COMT
levodopa antiparkinson agent DRD1
levodopa antiparkinson agent DRD2
levodopa antiparkinson agent DRD3
levodopa antiparkinson agent DRD4
levodopa antiparkinson agent DRD5
entinostat antineoplastic agent HDAC1
entinostat antineoplastic agent HDAC3
Enzastaurin antineoplastic agent PRKCB
EP217609 anticoagulant F10
EP217609 anticoagulant F2
EP42675 anticoagulant F10
EP42675 anticoagulant F2
EPI-743 for treatment of Chron's disease, for NQO1
treatment of ulcerative colitis
epinastine antiallergy agent HRH1
epinastine antiallergy agent HRH2
eplerenone antihypertensive agent NR3C2
eplivanserine for treatment of insomnia HTR2A
eplivanserine for treatment of insomnia HTR2C
Epothilone D antineoplastic agent TUBB1
eprotirome antidyslipidaemic agent THRB
erdosteine for treatment of chronic obstructive ELANE
pulmonary disorder (COPD)
eritoran for treatment of sepsis TLR4
Eslicarbazepine anticonvulsant SCN5A
esmirtazapine for treatment of insomnia, for ADRA2A
treatment of menopausal symptoms
esmirtazapine for treatment of insomnia, for HTR2A
treatment of menopausal symptoms
esmirtazapine for treatment of insomnia, for HTR3A
treatment of menopausal symptoms
esomeprazole Proton pump inhibitor ATP4A
estradiol contraceptive ESR1
estradiol contraceptive ESR1
estradiol contraceptive ESR2
norethisterone contraceptive PGR
estradiol for treatment of menopausal ESR1
symptoms
estradiol for treatment of menopausal ESR2
symptoms
estradiol for treatment of menopausal ESR1
symptoms
estradiol for treatment of menopausal ESR2
symptoms
estradiol contraceptive ESR1
dienogest contraceptive ESR1
dienogest contraceptive PGR
estradiol contraceptive ESR2
estradiol contraceptive ESR2
estradiol for treatment of menopausal ESR1
symptoms
estradiol for treatment of menopausal ESR2
symptoms
levonorgestrel for treatment of menopausal ESR1
symptoms
levonorgestrel for treatment of menopausal PGR
symptoms
levonorgestrel for treatment of menopausal SRD5A1
symptoms
estradiol for treatment of menopausal ESR1
symptoms
estradiol for treatment of menopausal ESR2
symptoms
estradiol for treatment of menopausal ESR1
symptoms
estradiol for treatment of menopausal ESR2
symptoms
drospirenone contraceptive AR
drospirenone contraceptive NR3C2
drospirenone contraceptive PGR
estradiol contraceptive ESR1
estradiol contraceptive ESR2
ethinyl estradiol contraceptive ESR1
levonorgestrel contraceptive ESR1
levonorgestrel contraceptive PGR
etilevodopa antiparkinson agent DRD1
etilevodopa antiparkinson agent DRD2
etilevodopa antiparkinson agent DRD3
etilevodopa antiparkinson agent DRD4
etilevodopa antiparkinson agent DRD5
etodolac NSAID PTGS2
etonogestrel contraceptive ESR1
etonogestrel contraceptive PGR
ethinyl estradiol contraceptive ESR1
etonogestrel contraceptive ESR1
etonogestrel contraceptive PGR
etoricoxib NSAID PTGS2
EV-077-3201-2TBS antidiabetic PPARG
everolimus immunosuppressant MTOR
raloxifen for treatment of menopausal ESR1
symptoms
raloxifen for treatment of menopausal ESR2
symptoms
metoclopramide for treatment of diabetic CHRM1
gastroparesis
metoclopramide for treatment of diabetic DRD2
gastroparesis
EVP-6124 nootropic CHRNA7
EVT-101 antidepressant GRIN2B
EVT-103 antidepressant GRIN2B
EVT-201 hypnotic GABRA2
EVT-201 hypnotic GABRA3
EVT-201 hypnotic GABRA5
EVT-201 hypnotic GABRA6
EVT-201 hypnotic GABRB1
EVT-201 hypnotic GABRB1
EVT-201 hypnotic GABRB2
EVT-201 hypnotic GABRB2
EVT-201 hypnotic GABRB3
EVT-201 hypnotic GABRD
EVT-201 hypnotic GABRD
EVT-201 hypnotic GABRE
EVT-201 hypnotic GABRG1
EVT-201 hypnotic GABRG2
EVT-201 hypnotic GABRG3
EVT-201 hypnotic GABRG3
EVT-201 hypnotic GABRP
EVT-201 hypnotic GABRQ
EVT-201 hypnotic GABRR2
EVT-302 smoking-cessation agent MA0B
EVT-401 antiinflammatory agent P2RX7
Exebryl-1 for treatment of alzheimer's disease APP
Exebryl-1 for treatment of alzheimer's disease MAPT
exemestane antineoplastic agent CYP19A1
ezatiostat for treatment of Myelodysplastic GSTP1
Syndrome
PEG-SN38 antineoplastic agent TOP1MT
PEG-SN38 antineoplastic agent TOP1
fentanyl analgesic OPRD1
fentanyl analgesic OPRM1
febuxostat for treatment of gout XDH
felodipine antihypertensive agent CACNA1C
felodipine antihypertensive agent CACNA1D
felodipine antihypertensive agent CACNA1S
felodipine antihypertensive agent CACNA2D1
felodipine antihypertensive agent CACNB2
fenoldopam antihypertensive agent DRD1
fenoldopam antihypertensive agent DRD5
fenretinide antineoplastic agent RARA
fenretinide antineoplastic agent RARB
fenretinide antineoplastic agent RARG
fentanyl analgesic OPRD1
fentanyl analgesic OPRM1
fentanyl analgesic OPRD1
fentanyl analgesic OPRM1
fentanyl analgesic OPRD1
fentanyl analgesic OPRM1
fentanyl analgesic OPRD1
fentanyl analgesic OPRM1
fentanyl analgesic OPRD1
fentanyl analgesic OPRM1
fentanyl analgesic OPRD1
fentanyl analgesic OPRM1
fentanyl analgesic OPRD1
fentanyl analgesic OPRM1
fentanyl analgesic OPRD1
fentanyl analgesic OPRM1
fesoterodine for treatment of overactive bladder CHRM3
syndrome
fexofenadine antiallergy agent HRH1
pseudoephedrine antiallergy agent ADRA1A
pseudoephedrine antiallergy agent ADRA2A
pseudoephedrine antiallergy agent SLC6A2
pseudoephedrine antiallergy agent SLC6A3
pseudoephedrine antiallergy agent SLC6A4
FG-2216 for treatment of anemia EGLN1
FG-2216 for treatment of anemia EGLN2
FG-2216 for treatment of anemia EGLN3
FG-4592 for treatment of anemia EGLN1
FG-4592 for treatment of anemia EGLN2
FG-4592 for treatment of anemia EGLN3
fingolimod for treatment of multiple sclerosis S1PR1
fipamezole antiparkinson agent ADRA2A
fipamezole antiparkinson agent ADRA2B
fipamezole antiparkinson agent ADRA2C
icatibant for treatment of hereditary BDKRB2
angioedema
fispemifene hormone replacement ESR1
fispemifene hormone replacement ESR2
FK352B antihypertensive agent ADORA1
alvocidib antineoplastic agent CDC2
alvocidib antineoplastic agent CDK10
alvocidib antineoplastic agent CDK2
alvocidib antineoplastic agent CDK3
alvocidib antineoplastic agent CDK4
alvocidib antineoplastic agent CDK5
alvocidib antineoplastic agent CDK6
alvocidib antineoplastic agent CDK7
alvocidib antineoplastic agent CDK8
alvocidib antineoplastic agent CDK9
flibanserin for treatment of female sexual HTR1A
dysfunction
flibanserin for treatment of female sexual HTR2A
dysfunction
flovagatran anticoagulant F2
fludarabine antineoplastic agent DCK
fludarabine antineoplastic agent POLA1
fludarabine antineoplastic agent RRM1
flunisolide antiinflammatory NR3C1
agent, glucocorticoid
flunisolide antiinflammatory NR3C1
agent, glucocorticoid
fluocinonide antiinflammatory NR3C1
agent, glucocorticoid
fluoxetine antidepressant SLC6A4
flupirtine analgesic KCNJ3
flupirtine analgesic KCNJ5
flupirtine analgesic KCNJ6
flupirtine analgesic KCNJ9
fluticasone antiinflammatory NR3C1
agent, glucocorticoid
fluvastatin antihypecholesterolemic agent HMGCR
fluvoxamine antidepressant SLC6A4
dexmethylphenidate for treatment of ADHD SLC6A3
dexmethylphenidate for treatment of ADHD SLCA2
forodesine antineoplastic agent PNP
formoterol bronchodilator ADRB2
formoterol for treatment of chronic obstructive ADRB2
pulmonary disorder (COPD)
fosphenytoin anticonvulsant SCN5A
fospropofol hypnotic and sedative GABRB2
fospropofol hypnotic and sedative GABRB3
fostamatinib antiinflammatory agent, DMARD SYK
cyclosporine immunosuppressant CAMLG
cyclosporine immunosuppressant PPP3R2
prednisolone antiinflammatory NR3C1
agent, corticosteroid
frovatriptan antimigraine agent HTR1B
frovatriptan antimigraine agent HTR1D
fruquintinib antineoplastic agent FLT1
fruquintinib antineoplastic agent FLT4
fruquintinib antineoplastic agent KDR
dexamethasone antiinflammatory NR3C1
agent, glucocorticoid, for treatment of
Meniere's disease
fulvestrant antineoplastic agent ESR1
leucovorin adjuvant to chemotherapy TYMS
FX125L antiasthmatic agent CCR1
FX125L antiasthmatic agent CXCR1
FX125L antiasthmatic agent CXCR2
FX125L antiasthmatic agent CXCR4
gabapentin analgesic CACNA1B
gabapentin analgesic CACNA2D1
gabapentin analgesic CACNA2D2
gaboxadol hypnotic GABRA2
gaboxadol hypnotic GABRA3
gaboxadol hypnotic GABRA5
gaboxadol hypnotic GABRA6
gaboxadol hypnotic GABRB1
gaboxadol hypnotic GABRB1
gaboxadol hypnotic GABRB2
gaboxadol hypnotic GABRB2
gaboxadol hypnotic GABRB3
gaboxadol hypnotic GABRD
gaboxadol hypnotic GABRE
gaboxadol hypnotic GABRG1
gaboxadol hypnotic GABRP
galantamine for treatment of alzheimer's disease ACHE
ganaxolone anticonvulsant GABRA1
ganaxolone anticonvulsant GABRA2
ganaxolone anticonvulsant GABRA3
ganaxolone anticonvulsant GABRA4
ganaxolone anticonvulsant GABRA5
ganaxolone anticonvulsant GABRA6
gantacurium muscle relaxant, neuromuscular CHRNA2
blocking agent
GDC-0068 antineoplastic agent AKT1
GDC-0068 antineoplastic agent AKT2
GDC-0068 antineoplastic agent AKT3
GDC-0973 antineoplastic agent MAP2K1
gemcitabine antineoplastic agent RRM1
gepirone antidepressant HTR1A
progesterone for prevention of preterm delivery PGR
GGTI-2418 antineoplastic agent FNTA
GGTI-2418 antineoplastic agent PGGT1B
GL1001 for treatment of Chron's disease, for ACE2
treatment of ulcerative colitis
glimepiride antidiabetic KCNJ1
glimepiride antidiabetic ABCC8
glimepiride antidiabetic KCNJ11
GLPG0187 antineoplastic agent ITGA5
GLPG0187 antineoplastic agent ITGAV
GLPG0187 antineoplastic agent ITGB1
GLPG0187 antineoplastic agent ITGB3
GLPG0187 antineoplastic agent ITGB5
GLPG0187 antineoplastic agent ITGB6
GLPG0259 antiinflammatory agent, DMARD MAPKAPK5
GLPG0492 for treatment of cachexia AR
GLPG0634 antiinflammatory agent, DMARD JAK1
GLPG0634 antiinflammatory agent, DMARD JAK2
Glufosfamide antineoplastic agent SLC2A1
Glufosfamide antineoplastic agent SLC2A2
Glufosfamide antineoplastic agent SLC2A3
Glufosfamide antineoplastic agent SLC2A4
Glufosfamide antineoplastic agent SLC2A5
Glufosfamide antineoplastic agent SLC5A1
Glufosfamide antineoplastic agent SLC5A2
Glufosfamide antineoplastic agent SLC5A4
glyburide antidiabetic ABCC8
metformin antidiabetic PRKAB1
glycopyrrolate antineoplastic agent CHRM1
GMI-1070 for treatment of sickle-cell disease SELE
GMI-1070 for treatment of sickle-cell disease SELL
GMI-1070 for treatment of sickle-cell disease SELP
GMX1777 antineoplastic agent NAMPT
NBI-42902 for treatment of postmenopausal GNRHR
symptoms, antineoplastic agent
NBI-42902 for treatment of postmenopausal GNRHR2
symptoms, antineoplastic agent
GPI-1485 antiparkinson agent FKBP1A
GPX-100 antineoplastic agent TOP2A
granisetron antiemetic HTR3A
granisetron antiemetic HTR3B
granisetron antiemetic HTR3C
granisetron antiemetic HTR3D
granisetron antiemetic HTR3E
granisetron antiemetic HTR3A
granisetron antiemetic HTR3B
granisetron antiemetic HTR3C
granisetron antiemetic HTR3D
granisetron antiemetic HTR3E
GS-9411 for treatment of pulmonary disease SCNN1A
GS-9411 for treatment of pulmonary disease SCNN1B
GS-9411 for treatment of pulmonary disease SCNN1D
GS-9411 for treatment of pulmonary disease SCNN1G
GSI-136 for treatment of Alzheimer's disease APH1A
GSI-136 for treatment of Alzheimer's disease APH1B
GSI-136 for treatment of Alzheimer's disease NCSTN
GSI-136 for treatment of Alzheimer's disease PSEN1
GSI-136 for treatment of Alzheimer's disease PSEN2
GSI-136 for treatment of Alzheimer's disease PSENEN
GSK-1004723 antiallergy agent HRH1
GSK-1004723 antiallergy agent HRH3
trametinib antineoplastic agent MAP2K1
GSK2118436 antineoplastic agent BRAF
GSK-961081 bronchodilator ADRB2
GSK-961081 bronchodilator CHRM3
GTS-21 for treatment of schizophrenia CHRNA7
GTx-758 antineoplastic agent LHCGR
guanfacine for treatment of ADHD ADRA2A
GW501516 antidyslipidaemic agent PPARA
GW501516 antidyslipidaemic agent PPARD
GW501516 antidyslipidaemic agent PPARG
GW642444 bronchodilator ADRB2
halofuginone antineoplastic agent EPRS
flurbiprofen antiinflammatory agent, NSAID PTGS2
nitric oxide antiinflammatory agent GUCY1A2
HE3235 antineoplastic agent AR
doxorubicin antineoplastic agent TOP2A
heparin anticoagulant F10
heparin anticoagulant SERPINC1
heparin anticoagulant F10
heparin anticoagulant SERPINC1
HF0220 for treatment of alzheimer's disease unknown
HGS1029 antineoplastic agent BIRC2
HGS1029 antineoplastic agent BIRC3
HGS1029 antineoplastic agent BIRC5
HGS1029 antineoplastic agent XIAP
amlodipine antihypertensive agent CACNA1C
amlodipine antihypertensive agent CACNA1D
amlodipine antihypertensive agent CACNA1S
amlodipine antihypertensive agent CACNA2D1
amlodipine antihypertensive agent CACNAB2
simvastatin antihypertensive agent HMGCR
amiloride antihypertensive agent SCNN1A
amiloride antihypertensive agent SCNN1B
amiloride antihypertensive agent SCNN1D
amiloride antihypertensive agent SCNN1G
spironolactone antihypertensive agent NR3C2
huperzine-A for treatment of Alzheimer's disease ACHE
hydralazine antihypertensive agent AOC3
isosorbide dinitrate antihypertensive agent NPR1
hydroxytamoxifen for treatment of cyclic mastalgia ESR1
hydroxytamoxifen for treatment of cyclic mastalgia ESR2
famotidine acid reducer HRH2
famotidine for treatment of gastric ulcer and HRH2
gastroesophageal reflux
ibuprofen NSAID PTGS1
ibuprofen NSAID PTGS2
ibandronate antiosteoporotic agent FDPS
dexamethasone antiinflammatory NR3C1
agent, glucocorticoid, for treatment of
Meniere's disease
ibudilast neuroprotectant PDE4A
ibudilast neuroprotectant PDE4B
ibudilast neuroprotectant PDE4C
ICA-105665 anticonvulsant KCNQ1
ICA-105665 anticonvulsant KCNQ2
ICA-105665 anticonvulsant KCNQ3
ICA-105665 anticonvulsant KCNQ4
ICA-105665 anticonvulsant KCNQ5
idrabiotaparinux antithrombotic F10
idraparinux antithrombotic F10
iferanserin antihemorrhoidal agent HTR2A
iloperidone antipsychotic agent, atypical ADRA1A
iloperidone antipsychotic agent, atypical ADRA2C
iloperidone antipsychotic agent, atypical DRD1
iloperidone antipsychotic agent, atypical DRD2
iloperidone antipsychotic agent, atypical DRD3
iloperidone antipsychotic agent, atypical HRH1
iloperidone antipsychotic agent, atypical HTR1A
iloperidone antipsychotic agent, atypical HTR2A
iloperidone antipsychotic agent, atypical HTR6
iloperidone antipsychotic agent, atypical HTR7
iloprost antihypertensive agent PTGER1
iloprost antihypertensive agent PTGIR
fluocinolone acetonide antiinflammatory NR3C1
agent, glucocorticoid
imatinib antineoplastic agent ABL1
imatinib antineoplastic agent CSF1R
imatinib antineoplastic agent DDR1
imatinib antineoplastic agent KIT
imatinib antineoplastic agent NTRK1
imatinib antineoplastic agent PDGFRA
imatinib antineoplastic agent PDGFRB
imatinib antineoplastic agent RET
Imiquimod anti wart agent, antineoplastic agent TLR7
implitapide antiatherosclerotic agent MTTP
INCB13739 antidiabetic HSD11B1
INCB18424 antineoplastic JAK1
agent, antiinflammatory agent
INCB18424 antineoplastic JAK2
agent, antiinflammatory agent
INCB3284 antiinflammatory agent, DMARD CCR2
INCB7839 antineoplastic agent ADAM10
INCB7839 antineoplastic agent ADAM17
indacaterol bronchodilator ADRB2
indomethacin NSAID KCNE1
indomethacin NSAID KCNQ1
Indiplon hypnotic GABRA1
inecalcitol antineoplastic agent, prostate cancer VDR
apomorphine for treatment of sexual dysfunction in DRD2
women, for treatment of erectile
dysfunction, antiparkinson agent
apomorphine for treatment of sexual dysfunction in DRD3
women, for treatment of erectile
dysfunction, antiparkinson agent
apomorphine for treatment of sexual dysfunction in DRD4
women, for treatment of erectile
dysfunction, antiparkinson agent
atropine nerve agent antidote CHRM1
atropine nerve agent antidote CHRM2
atropine nerve agent antidote CHRM3
atropine nerve agent antidote CHRM4
atropine nerve agent antidote CHRM5
iniparib antineoplastic agent PARP1
INK128 antineoplastic agent CRTC1
INK128 antineoplastic agent CRTC2
INNO-206 antineoplastic agent TOP2A
INO-8875 for treatment of glaucoma ADORA1
INS37217 for treatment of rhegmatogenous P2RY2
retinal detachment
INS37217 for treatment of cystic fibrosis, for P2RY2
treatment of perennial allergic
rhinitis
INSM-18 antineoplastic agent, prostate cancer ERBB2
INSM-18 antineoplastic agent, prostate cancer IGF1R
AMG-131 antidiabetic PPARG
apomorphine for treatment of sexual dysfunction in DRD2
women, for treatment of erectile
dysfunction, antiparkinson agent
apomorphine for treatment of sexual dysfunction in DRD3
women, for treatment of erectile
dysfunction, antiparkinson agent
apomorphine for treatment of sexual dysfunction in DRD4
women, for treatment of erectile
dysfunction, antiparkinson agent
ketorolac NSAID PTGS2
morphine analgesic OPRD1
morphine analgesic OPRK1
morphine analgesic OPRM1
retaspimycin antineoplastic agent HSP90AA1
retaspimycin antineoplastic agent HSP90AA2
retaspimycin antineoplastic agent HSP90AB1
IPI-504 antineoplastic agent HSP90AA1
IPI-504 antineoplastic agent HSP90AA2
IPI-504 antineoplastic agent HSP90AB1
IPI-940 analgesic FAAH
ipratropium for treatment of chronic obstructive CHRM1
pulmonary disorder (COPD)
ipratropium for treatment of chronic obstructive CHRM2
pulmonary disorder (COPD)
salbutamol for treatment of chronic obstructive ADRB2
pulmonary disorder (COPD)
IPX066 antiparkinson agent DDC
irbesartan antihypertensive agent AGTR1
gefitinib antineoplastic agent EGFR
irinotecan antineoplastic agent TOP1
isofa*gomine for treatment of Gaucher's disease GBA
ispinesib antineoplastic agent KIF11
istaroxime for treatment of heart failure ATP1A1
istaroxime for treatment of heart failure ATP2A2
istradefylline antiparkinson agent ADORA2A
bromfenac opthalmological agent, NSAID PTGS1
bromfenac opthalmological agent, NSAID PTGS2
bromfenac opthalmological agent, NSAID PTGS1
bromfenac opthalmological agent, NSAID PTGS2
Givinostat antineoplastic HDAC1
agent, antiinflammatory agent
Givinostat antineoplastic HDAC10
agent, antiinflammatory agent
Givinostat antineoplastic HDAC2
agent, antiinflammatory agent
Givinostat antineoplastic HDAC3
agent, antiinflammatory agent
Givinostat antineoplastic HDAC4
agent, antiinflammatory agent
Givinostat antineoplastic HDAC5
agent, antiinflammatory agent
Givinostat antineoplastic HDAC6
agent, antiinflammatory agent
Givinostat antineoplastic HDAC7
agent, antiinflammatory agent
Givinostat antineoplastic HDAC8
agent, antiinflammatory agent
Givinostat antineoplastic HDAC9
agent, antiinflammatory agent
ITI-007 antipsychotic agent DRD2
ITI-007 antipsychotic agent HTR2A
ITI-007 antipsychotic agent PPP1R1B
ITI-007 antipsychotic agent SLC6A4
itopride motilitant ACHE
itopride motilitant DRD2
IW-6118 analgesic FAAH
ixabepilone antineoplastic agent TUBB3
JB991 antiinflammatory PPARG
agent, dermatologic agent
JNJ-37822681 antipsychotic agent DRD2
JSM 6427 for treatment of age-related macular ITGA5
degeneration
JSM 6427 for treatment of age-related macular ITGB1
degeneration
ropinirole for treatment of restlegs legs DRD2
syndrome
ropinirole for treatment of restlegs legs DRD3
syndrome
ropinirole for treatment of restlegs legs DRD4
syndrome
clonazepam anticonvulsant GABRA2
clonazepam anticonvulsant GABRA3
clonazepam anticonvulsant GABRA5
clonazepam anticonvulsant GABRA6
clonazepam anticonvulsant GABRB1
clonazepam anticonvulsant GABRB1
clonazepam anticonvulsant GABRB2
clonazepam anticonvulsant GABRB2
clonazepam anticonvulsant GABRB3
clonazepam anticonvulsant GABRD
clonazepam anticonvulsant GABRD
clonazepam anticonvulsant GABRE
clonazepam anticonvulsant GABRG2
clonazepam anticonvulsant GABRG3
clonazepam anticonvulsant GABRG3
clonazepam anticonvulsant GABRP
clonazepam anticonvulsant GABRQ
clonazepam anticonvulsant GABRR2
Karenitecin antineoplastic agent TOP1
KC706 antiinflammatory agent, DMARD MAPK11
KC706 antiinflammatory agent, DMARD MAPK12
KC706 antiinflammatory agent, DMARD MAPK13
KC706 antiinflammatory agent, DMARD MAPK14
KD3010 antiobesity agent, for treatment of PPARD
metabolic disorders
ketoprofen NSAID PTGS1
ketoprofen NSAID PTGS2
ketoprofen NSAID PTGS1
ketoprofen NSAID PTGS1
ketoprofen NSAID PTGS2
ketoprofen NSAID PTGS2
ketorolac NSAID PTGS1
ketorolac NSAID PTGS2
ketotifen antiallergy agent HRH1
ketoprofen NSAID PTGS1
ketoprofen NSAID PTGS1
ketoprofen NSAID PTGS2
ketoprofen NSAID PTGS2
KN38-7271 neuroprotectant CNR1
KN38-7271 neuroprotectant CNR2
KOS-2187 for treatment of gastrointestinal MLNR
motility disorders
kp201 analgesic OPRD1
kp201 analgesic OPRK1
kp201 analgesic OPRM1
KRP-104 antidiabetic DPP4
KUC-7483 for treatment of overactive bladder ADRB3
KX2-391 antineoplastic agent SRC
granisetron antiemetic HTR3A
Lacosamide anticonvulsant, analgesic, neuropathic DPYSL2
pain
lamotrigine anticonvulsant SCN2A
lanreotide for treatment of acromegaly SSTR1
lanreotide for treatment of acromegaly SSTR5
lansoprazole antiulcer agent ATP4A
lansoprazole antiulcer agent ATP4A
LAS-100977 bronchodilator ADRB2
lasmiditan antimigraine agent HTR1F
lasofoxifene antiosteoporotic agent, hormone ESR1
replacement therapy
latanoprost for treatment of glaucoma PTGFR
timolol for treatment of glaucoma ADRB1
timolol for treatment of glaucoma ADRB2
latanoprost for treatment of glaucoma PTGFR
latanoprost for treatment of glaucoma PTGFR
atorvastatin anticholesterolaemic agent HMGCR
fenofibrate anticholesterolaemic agent PPARA
fenofibrate anticholesterolaemic agent PPARA
sirolimus immunosuppressant FGF2
sirolimus immunosuppressant FKBP1A
sirolimus immunosuppressant FRAP1
Erismodegib antineoplastic agent SMO
LEE011 antineoplastic agent CDK4
LEE011 antineoplastic agent CDK6
lercanidipine antihypertensive agent CACNG1
LE-SN38 antineoplastic agent TOP1
LE-SN38 antineoplastic agent TOP1MT
lesogaberan for treatment of gastrointestinal GABBR1
reflux disease
lesogaberan for treatment of gastrointestinal GABBR2
reflux disease
lestaurtinib antineoplastic agent FLT3
lestaurtinib antineoplastic agent NTRK1
lestaurtinib antineoplastic agent NTRK2
lestaurtinib antineoplastic agent NTRK3
lestaurtinib antineoplastic agent JAK2
ambrisentan antihypertensive agent EDNRA
ambrisentan antihypertensive agent EDNRB
letrozole antineoplastic agent CYP19A1
salbutamol bronchodilator ADRB2
levetiracetam anticonvulsant CACNA1B
levetiracetam anticonvulsant SV2A
levocetirizine antiallergy agent HRH1
levodopa antiparkinson agent DRD1
levodopa antiparkinson agent DRD2
levodopa antiparkinson agent DRD3
levodopa antiparkinson agent DRD4
levodopa antiparkinson agent DRD5
levomilnacipran antidepressant SLC6A2
levomilnacipran antidepressant SLC6A4
ethinyl estradiol contraceptive ESR1
levonorgestrel contraceptive ESR1
levonorgestrel contraceptive PGR
levonorgestrel contraceptive SRD5A1
Levosimendan for treatment of heart failure KCNJ11
Levosimendan for treatment of heart failure TNNC1
levothyroxine hormone replacement THRA
levothyroxine hormone replacement THRB
levothyroxine hormone replacement THRA
levothyroxine hormone replacement THRB
LGD-1550 antineoplastic agent RARA
LGD-1550 antineoplastic agent RARB
LGD-1550 antineoplastic agent RARG
LGD-2941 antiosteoporotic agent AR
LGD-4033 hormone replacement AR
LGD-4665 thrombopoietic agent MPL
Liarozole dermatological agent, for treatment of CYP26A1
ichtyosis
licarbazepine for treatment of bipolar disorder SCN5A
licofelone antiinflammatory agent ALOX5
licofelone antiinflammatory agent PTGS2
lidocaine anestethic SCN9A
lidocaine anestethic SCN10A
lidocaine anestethic SCN5A
piroxicam antiinflammatory agent, NSAID PTGS2
lidocaine anestethic SCN10A
lidocaine anestethic SCN5A
lidocaine anestethic SCN9A
lidocaine anestethic SCN10A
lidocaine anestethic SCN5A
lidocaine anestethic SCN9A
lidocaine anestethic SCN10A
lidocaine anestethic SCN5A
lidocaine anestethic SCN9A
LIM-0705 for improving pharmaco*kinetics of ABCA5
tacrolimus
LIM-0705 for improving pharmaco*kinetics of ABCB1
tacrolimus
Linaglipton antidiabetic DPP4
fluticasone propionate for treatment of symptomatic NR3C1
exophthalmos associated with
thyroid-related eye disease
salbutamol for treatment of symptomatic ADRB2
exophthalmos associated with
thyroid-related eye disease
docetaxel antineoplastic agent BCL2
docetaxel antineoplastic agent TUBB1
doxorubicin antineoplastic agent TOP2A
pacl*taxel antineoplastic agent TOP2A
lurtotecan antineoplastic agent TOP1
mitoxantrone antineoplastic agent TOP2A
prednisolone antiinflammatory NR3C1
agent, corticosteroid
Lipotecan antineoplastic agent TOP1
lisinopril antihypertensive agent ACE
Lisofylline antidiabetic STAT4
lixivaptan for treatment of hyponatremia AVPR2
Lobeline for treatment of metamphetamine SLC18A2
addicton
lofexidine for treatment of opiate withdrawal ADRA2A
lofexidine for treatment of opiate withdrawal ADRA2B
lofexidine for treatment of opiate withdrawal ADRA2C
lomitapide anticholesterolaemic agent MTTP
LOR-253 antineoplastic agent MTF1
loratadine antiasthmatic agent HRH1
montelukast antiasthmatic agent CYSLTR1
Lorcaserin antiobesity agent HTR2C
loteprednol etabonate antiinflammatory NR3C1
agent, corticosteroid
methamphetamine neuroprotectant ADRA2A
methamphetamine neuroprotectant ADRA2B
methamphetamine neuroprotectant ADRA2C
methamphetamine neuroprotectant MAOA
methamphetamine neuroprotectant MAOB
methamphetamine neuroprotectant SLC18A1
methamphetamine neuroprotectant SLC18A2
methamphetamine neuroprotectant SLC6A2
methamphetamine neuroprotectant SLC6A3
methamphetamine neuroprotectant SLC6A4
methamphetamine neuroprotectant TAAR1
lovastatin anticholesterolaemic agent HMGCR
enoxaparin anticoagulant F2
vortioxetine antidepressant HTR1A
vortioxetine antidepressant HTR1B
vortioxetine antidepressant HTR3A
vortioxetine antidepressant HTR7
vortioxetine antidepressant SLC6A4
Tedatioxetine antidepressant ADRA1A
Tedatioxetine antidepressant HTR2C
Tedatioxetine antidepressant HTR2C
Tedatioxetine antidepressant HTR3A
Tedatioxetine antidepressant SLC6A2
Tedatioxetine antidepressant SLC6A3
Tedatioxetine antidepressant SLC6A4
zicronapine antipsychotic agent DRD4
Lu-AE58054 antipsychotic agent HTR6
Lubiprostone motilitant, for treatment of irritable CLCN2
bowel disorder
lumiracoxib NSAID PTGS2
eszopiclone hypnotic GABRA1
eszopiclone hypnotic GABRA2
eszopiclone hypnotic GABRA3
eszopiclone hypnotic GABRA5
eszopiclone hypnotic TSPO
lurasidone antipsychotic agent ADRA2C
lurasidone antipsychotic agent DRD2
lurasidone antipsychotic agent HTR1A
lurasidone antipsychotic agent HTR2A
lurasidone antipsychotic agent HTR7
LX1031 for treatment of irritable bowel TPH1
syndrome
LX1032 for treatment of carcinoid syndrome TPH1
cyclosporine A immunosuppressant, opthalmological CAMLG
agent
cyclosporine A immunosuppressant, opthalmological PPP3R2
agent
LX4211 antidiabetic SLC5A1
LX4211 antidiabetic SLC5A2
LY2140023 antipsychotic agent GRM2
LY2140023 antipsychotic agent GRM3
LY3009104 antiinflammatory agent, DMARD JAK1
LY3009104 antiinflammatory agent, DMARD JAK2
semagacestat for treatment of Alzheimer's disease PSEN1
semagacestat for treatment of Alzheimer's disease PSEN2
LY-517717 anticoagulant F10
naveglitazar antidiabetic PPARA
naveglitazar antidiabetic PPARG
LY-674 anticholesterolaemic agent PPARA
M0002 for treatemnt of ascites AVPR2
heparin anticoagulant F10
heparin anticoagulant HPSE
heparin anticoagulant SERPINC1
morphine analgesic OPRD1
morphine analgesic OPRK1
morphine analgesic OPRM1
macitentan cardiovascular agent EDNRA
macitentan cardiovascular agent EDNRB
dihydroergotamine antimigraine agent HTR1B
dihydroergotamine antimigraine agent HTR1D
budesonide antiinflammatory NR3C1
agent, glucocorticoid
formoterol bronchodilator ADRB2
budesonide antiinflammatory NR3C1
agent, glucocorticoid
masitinib antiinflammatory ABL1
agent, DMARD, antineoplastic agent
masitinib antiinflammatory CSF1R
agent, DMARD, antineoplastic agent
masitinib antiinflammatory HCK
agent, DMARD, antineoplastic agent
masitinib antiinflammatory KIT
agent, DMARD, antineoplastic agent
masitinib antiinflammatory LYN
agent, DMARD, antineoplastic agent
masitinib antiinflammatory PDGFRA
agent, DMARD, antineoplastic agent
masitinib antiinflammatory PDGFRB
agent, DMARD, antineoplastic agent
masitinib antiinflammatory SRC
agent, DMARD, antineoplastic agent
mesalazine for treatment of ulcerative proctitis ALOX5
mesalazine for treatment of ulcerative proctitis PPARG
mesalazine for treatment of ulcerative proctitis PTGS1
mesalazine for treatment of ulcerative proctitis PTGS2
MB07811 antidyslipidaemic agent THRB
MBX-2044 antidiabetic PPARG
MBX-2982 antidiabetic GPR119
MBX-8025 antidyslipidaemic agent PPARD
lisinopril antihypertensive agent ACE
lisinopril antihypertensive agent ACE2
MC-1 cardioprotectant LPAR4
MC-1 cardioprotectant LPAR6
MC-1 cardioprotectant P2RY1
MC-1 cardioprotectant P2RY10
MC-1 cardioprotectant P2RY11
MC-1 cardioprotectant P2RY12
MC-1 cardioprotectant P2RY13
MC-1 cardioprotectant P2RY14
MC-1 cardioprotectant P2RY2
MC-1 cardioprotectant P2RY4
MC-1 cardioprotectant P2RY6
MC-1 cardioprotectant P2RY8
MCD-386 for treatment of Alzheimer's disease CHRM1
MDAM antineoplastic agent DHFR
MDV3100 antineoplastic agent AR
Mebendazole antineoplastic agent TUBA1A
Mebendazole antineoplastic agent TUBB2C
mecamylamine for treatment of ADHD CHRNA2
melogliptin antidiabetic DPP4
MEM 1003 for treatment of Alzheimer's disease CACNA1C
MEM 1003 for treatment of Alzheimer's disease CACNA1D
MEM 1003 for treatment of Alzheimer's disease CACNA1F
MEM 1003 for treatment of Alzheimer's disease CACNA1S
MEM 1414 for treatment of Alzheimer's disease PDE4A
MEM 1414 for treatment of Alzheimer's disease PDE4B
MEM 63908 for treatment of Alzheimer's disease CHRNA7
MEM3454 for treatment of Alzheimer's disease CHRNA7
memantine for treatment of glaucoma GRIN2A
memantine for treatment of glaucoma GRIN2B
memantine for treatment of glaucoma GRIN3A
vorinostat antineoplastic agent HDAC1
vorinostat antineoplastic agent HDAC2
vorinostat antineoplastic agent HDAC3
vorinostat antineoplastic agent HDAC6
mesalamine antiinflammatory agent ALOX5
mesalamine antiinflammatory agent PPARG
mesalamine antiinflammatory agent PTGS1
mesalamine antiinflammatory agent PTGS2
WX-671 antineoplastic agent PLAU
Oxypurinol for treatment of heart failure, for XDH
treatment of gout
metaglidasen antidiabetic PPARG
metformin antidiabetic PRKAB1
metformin antidiabetic PRKAB1
metformin antidiabetic PRKAB1
Methylnaltrexone for treatment of opioid-induced OPRM1
constipation
methylphenidate for treatment of ADHD SLC6A2
methylphenidate for treatment of ADHD SLC6A3
methylphenidate for treatment of ADHD SLC6A4
methylphenidate for treatment of ADHD SLC6A2
methylphenidate for treatment of ADHD SLC6A3
methylphenidate for treatment of ADHD SLC6A4
methylphenidate for treatment of ADHD SLC6A2
methylphenidate for treatment of ADHD SLC6A3
methylphenidate for treatment of ADHD SLC6A4
methyltestosterone for treatment of dysfunctional libido AR
in women
metoclopramide motilitant, for treatment of CHRM1
gastroesophageal reflux disease
metoclopramide motilitant, for treatment of DRD2
gastroesophageal reflux disease
metoclopramide antiemetic CHRM1
metoclopramide antiemetic DRD2
metoprolol antihypertensive agent ADRB1
MF101 for treatment of menopausal ESR2
symptoms
MGCD-0103 antineoplastic agent HDAC1
MGCD-0103 antineoplastic agent HDAC10
MGCD-0103 antineoplastic agent HDAC11
MGCD-0103 antineoplastic agent HDAC2
MGCD-0103 antineoplastic agent HDAC3
MGCD-0103 antineoplastic agent HDAC4
MGCD-0103 antineoplastic agent HDAC5
MGCD-0103 antineoplastic agent HDAC6
MGCD-0103 antineoplastic agent HDAC7A
MGCD-0103 antineoplastic agent HDAC8
MGCD-0103 antineoplastic agent HDAC9
MGCD265 antineoplastic agent FLT1
MGCD265 antineoplastic agent FLT4
MGCD265 antineoplastic agent KDR
MGCD265 antineoplastic agent MET
MGCD265 antineoplastic agent MST1R
MGCD265 antineoplastic agent TEK
morphine analgesic OPRD1
morphine analgesic OPRK1
morphine analgesic OPRM1
pacl*taxel antiinflammatory agent, DMARD BCL2
pacl*taxel antiinflammatory agent, DMARD TUBB1
Midostaurin antineoplastic agent FLT3
Mifepristone opthalmological agent, for lowering NR3C1
intraocular pressure
Mifepristone opthalmological agent, for lowering PGR
intraocular pressure
Mifepristone antipsychotic, antidepressant NR3C1
Mifepristone antipsychotic, antidepressant PGR
migalastat enzyme replacement therapy, for GLA
treatment of Fabry disease
miglustat for treatment of Gaucher's disease UGCG
milataxel antineoplastic agent BCL2
milataxel antineoplastic agent TUBB1
Milnacipran for treatment of fibromyalgia SLC6A2
syndrome
Milnacipran for treatment of fibromyalgia SLC6A4
syndrome
milveterol bronchodilator ADRB2
MIM-D3 opthalmological agent NTRK1
minodronate antineoplastic agent FDPS
pramipexole antiparkinson agent DRD2
pramipexole antiparkinson agent DRD3
pramipexole antiparkinson agent DRD4
mirtazapine antidepressant ADRA2A
mirtazapine antidepressant HTR2A
mirtazapine antidepressant HTR3A
mitemcinal for treatment of gastroparesis MLNR
mitiglinide antidiabetic ABCC8
mitoxantrone antineoplastic agent TOP2A
MIV-701 for treatment of osteoporosis CTSK
laropiprant for counteracting niacin-induced PTGDR
flushing
niacin antidyslipidaemic agent GPR109A
niacin antidyslipidaemic agent GPR109B
niacin antidyslipidaemic agent NNMT
niacin antidyslipidaemic agent QPRT
laropiprant for counteracting niacin-induced PTGDR
flushing
niacin antidyslipidaemic agent GPR109A
niacin antidyslipidaemic agent GPR109B
niacin antidyslipidaemic agent NNMT
niacin antidyslipidaemic agent QPRT
simvastatin anticholesterolaemic agent HMGCR
MK-1775 antineoplastic agent WEE1
MK-2206 antineoplastic agent AKT1
MK-2206 antineoplastic agent AKT2
MK-2206 antineoplastic agent AKT3
suvorexant hypnotic HCRTR1
suvorexant hypnotic HCRTR2
MK-4827 antineoplastic agent PARP1
MK-4827 antineoplastic agent PARP2
MKC-1 antineoplastic agent IPO11
MKC-1 antineoplastic agent IPO13
MKC-1 antineoplastic agent IPO4
MKC-1 antineoplastic agent IPO7
MKC-1 antineoplastic agent IPO8
MKC-1 antineoplastic agent IPO9
MKC-1 antineoplastic agent TUBB
MKC-1 antineoplastic agent TUBB1
MLN-0415 antiinflammatory agent IKBKB
MLN-4924 antineoplastic agent UBA3
MLN-8054 antineoplastic agent AUR2
MLN-8237 antineoplastic agent AURKA
MLN-9708 antineoplastic agent PSMB1
MLN-9708 antineoplastic agent PSMB2
MLN-9708 antineoplastic agent PSMB5
MLN-9708 antineoplastic agent PSMD1
MLN-9708 antineoplastic agent PSMD2
MN-201 antineoplastic agent VDR
MN-246 for treatment of overactive bladder ADRB3
MN-305 antidepressant, hypnotic HTR1A
moclobemide antidepressant MAOA
modafinil central nervous system stimulant SLC6A3
Modufolin antineoplastic agent TYMS
formoterol antiasthmatic agent ADRB2
mometasone antiinflammatory NR3C1
agent, glucocorticoid
montelukast antiasthmatic agent CYSLTR1
morphine analgesic OPRD1
morphine analgesic OPRK1
morphine analgesic OPRM1
morphine analgesic OPRK1
morphine analgesic OPRK1
morphine analgesic OPRK1
dextromethorphan analgesic GRIN3A
dextromethorphan analgesic SIGMAR1
morphine analgesic OPRD1
morphine analgesic OPRK1
morphine analgesic OPRM1
morphine analgesic OPRD1
morphine analgesic OPRK1
morphine analgesic OPRM1
naltrexone analgesic OPRD1
naltrexone analgesic OPRK1
naltrexone analgesic OPRM1
naltrexone analgesic SIGMAR1
mosapride for treatment of Gastrointestinal HTR4
reflux disease (GERD)
motesanib antineoplastic agent FLT1
motesanib antineoplastic agent FLT4
motesanib antineoplastic agent KDR
motesanib antineoplastic agent KIT
motesanib antineoplastic agent PDGFRA
motesanib antineoplastic agent PDGFRB
motexafin gadolinium antineoplastic agent RRM1
motexafin gadolinium antineoplastic agent RRM2
motexafin gadolinium antineoplastic agent RRM2B
motexafin gadolinium antineoplastic agent TXNRD1
motexafin gadolinium antineoplastic agent TXNRD2
motexafin gadolinium antineoplastic agent TXNRD3
morphine analgesic OPRD1
morphine analgesic OPRK1
morphine analgesic OPRM1
oxycodone analgesic OPRM1
oxycodone analgesic OPRM1
oxycodone analgesic OPRM1
plerixafor antineoplastic agent CXCR4
MP0112 for treatment of diabetic retinopathy FLT1
MP0112 for treatment of diabetic retinopathy KDR
amuvatinib antineoplastic agent FLT3
amuvatinib antineoplastic agent KIT
amuvatinib antineoplastic agent MET
amuvatinib antineoplastic agent PDGFRA
amuvatinib antineoplastic agent PDGFRB
amuvatinib antineoplastic agent RAD51
amuvatinib antineoplastic agent RET
MPC-0920 antithrombotic F2
MPI-674 for treatment of abnormal uterine CYP19A1
bleeding (AUB)
MPI-676 for treatment of endometriosis CYP19A1
nitroglycerin for treatment of Raynaud's disease NPR1
MRX-4 antiinflammatory agent PLA2G3
MRX-6 antiinflammatory agent PLA2G3
mitoglitazone antidiabetic PPARG
talniflumate for treatment of cystic fibrosis CLCA1
MSX-122 antineoplastic agent CXCR4
metoclopramide antimigraine agent CHRM1
metoclopramide antimigraine agent DRD2
naproxen antimigraine agent PTGS1
naproxen antimigraine agent PTGS2
dihydroergotamine antimigraine agent HTR1B
dihydroergotamine antimigraine agent HTR1D
naproxen antimigraine agent PTGS1
naproxen antimigraine agent PTGS2
sumatriptan antimigraine agent HTR1A
sumatriptan antimigraine agent HTR1B
sumatriptan antimigraine agent HTR1D
sumatriptan antimigraine agent HTR1F
doxorubicin antineoplastic agent TOP2A
isothiourea antihypertensive agent NOS1
isothiourea antihypertensive agent NOS2
isothiourea antihypertensive agent NOS3
muraglitazar antidiabetic PPARA
muraglitazar antidiabetic PPARG
mycophenolic acid immunosuppressant IMPDH1
mycophenolic acid immunosuppressant IMPDH2
MPC-3100 antineoplastic agent HSP90AA1
MPC-3100 antineoplastic agent HSP90AB1
docetaxel antineoplastic agent BCL2
docetaxel antineoplastic agent TUBB1
nabilone antiemetic CNR1
nabilone antiemetic CNR2
nalbuphine analgesic OPRD1
nalbuphine analgesic OPRK1
nalbuphine analgesic OPRM1
nalmefene smoking-cessation agent, for OPRD1
treatment of addiction
nalmefene smoking-cessation agent, for OPRK1
treatment of addiction
nalmefene smoking-cessation agent, for OPRM1
treatment of addiction
memantine for treatment of Alzheimer's disease GRIN2A
memantine for treatment of Alzheimer's disease GRIN2B
memantine for treatment of Alzheimer's disease GRIN3A
diclofenac NSAID PTGS1
diclofenac NSAID PTGS2
Naproxcinod NSAID GUCY1A2
Naproxcinod NSAID PTGS1
Naproxcinod NSAID PTGS2
esomeprazole Proton pump inhibitor ATP4A
naproxen NSAID PTGS1
naproxen NSAID PTGS2
naproxen etemesil NSAID PTGS1
naproxen etemesil NSAID PTGS2
naratriptan antimigraine agent HTR1A
naratriptan antimigraine agent HTR1B
naratriptan antimigraine agent HTR1D
naratriptan antimigraine agent HTR1F
ketamine analgesic GRIN3A
ketamine analgesic GRIN3A
Nav 1.7 blocker analgesic SCN9A
NB-1011 antineoplastic agent TYMS
NBI-56418 antineoplastic agent GNRHR
NBI-98854 antipsychotic agent SLC18A2
NCX 1510 antiallergy agent GUCY1A2
NCX 1510 antiallergy agent HRH1
NCX 4016 antithrombotic GUCY1A2
NCX 4016 antithrombotic PTGS1
NCX 4016 antithrombotic PTGS2
carbidopa antiparkinson agent DDC
nebivolol antihypertensive agent ADRB1
nelarabine antineoplastic agent POLA1
nepicastat for treatment of addiction, for DBH
treatment of post-traumatic stress
disorder
neramexane for treatment of Alzheimer's disease GRIN2A
neramexane for treatment of Alzheimer's disease GRIN2B
neramexane for treatment of Alzheimer's disease GRIN3A
neratinib antineoplastic agent EGFR
neratinib antineoplastic agent ERBB2
ethinyl estradiol contraceptive ESR1
progestin contraceptive PGR
Neu-2000 cardioprotectant GRIN1
Neu-2000 cardioprotectant GRIN2A
Neu-2000 cardioprotectant GRIN2B
Neu-2000 cardioprotectant GRIN2C
Neu-2000 cardioprotectant GRIN2D
Neu-2000 cardioprotectant GRIN3A
Neu-2000 cardioprotectant GRIN3B
rotigotine antiparkinson agent DRD2
rotigotine antiparkinson agent DRD3
rotigotine antiparkinson agent DRD4
sorafenib antineoplastic agent BRAF
sorafenib antineoplastic agent FLT3
sorafenib antineoplastic agent FLT4
sorafenib antineoplastic agent KDR
sorafenib antineoplastic agent KIT
sorafenib antineoplastic agent PDGFRB
sorafenib antineoplastic agent RAF1
NG2-73 hypnotic GABRA2
NG2-73 hypnotic GABRA3
NG2-73 hypnotic GABRA5
NG2-73 hypnotic GABRA6
NG2-73 hypnotic GABRB1
NG2-73 hypnotic GABRB1
NG2-73 hypnotic GABRB2
NG2-73 hypnotic GABRB2
NG2-73 hypnotic GABRB3
NG2-73 hypnotic GABRD
NG2-73 hypnotic GABRD
NG2-73 hypnotic GABRE
NG2-73 hypnotic GABRG1
NG2-73 hypnotic GABRG2
NG2-73 hypnotic GABRG3
NG2-73 hypnotic GABRG3
NG2-73 hypnotic GABRP
NG2-73 hypnotic GABRQ
NG2-73 hypnotic GABRR2
NGD-4715 appetite suppressant MCHR1
NGD-8243 analgesic TRPV1
NGX267 for treatment of dry mouth CHRM1
niacin receptor agonist antiatherosclerotic agent HCAR2
niacin receptor agonist antiatherosclerotic agent HCAR3
NIC5-15 for treatment of Alzheimer's disease APH1A
NIC5-15 for treatment of Alzheimer's disease PSENEN
nilotinib antineoplastic agent ABL1
nitisinone for treatment of restlegs legs HPD
syndrome, for treatment of hereditary
tyrosinemia type 1 (HT-1)
PEG-irinotecan antineoplastic agent TOP1
PEG-irinotecan antineoplastic agent TOP1MT
PEG-docetaxel antineoplastic agent BCL2
PEG-docetaxel antineoplastic agent TUBB1
PEG-naloxol for treatment of opioid-induced OPRM1
constipation
NM-702 for treatment of intermittent PDE3A
claudication
NM-702 for treatment of intermittent PDE3B
claudication
hydromorphone analgesic OPRD1
hydromorphone analgesic OPRK1
hydromorphone analgesic OPRM1
NMS-1116354 antineoplastic agent CDC7
NNZ-2566 neuroprotectant IGF1
ethinyl estradiol contraceptive ESR1
norelgestromin contraceptive ESR1
norelgestromin contraceptive PGR
noscapine antineoplastic agent HIF1A
latanoprost for treatment of glaucoma PTGFR
Cyclosporine A immunosuppressant, opthalmological CAMLG
agent
Cyclosporine A immunosuppressant, opthalmological PPP3R2
agent
sumatriptan antimigraine agent HTR1A
sumatriptan antimigraine agent HTR1B
sumatriptan antimigraine agent HTR1D
sumatriptan antimigraine agent HTR1F
17-beta estradiol opthalmological agent ESR1
17-beta estradiol opthalmological agent ESR2
Fluoxetine for treatment of autism HTR2A
Fluoxetine for treatment of autism SLC6A4
NPS-2143 antiosteoporotic agent CASR
diazepam anticonvulsant GABRA1
diazepam anticonvulsant GABRA2
diazepam anticonvulsant GABRA3
diazepam anticonvulsant GABRA5
diazepam anticonvulsant GABRB1
diazepam anticonvulsant GABRB2
diazepam anticonvulsant GABRB3
diazepam anticonvulsant GABRD
diazepam anticonvulsant GABRE
diazepam anticonvulsant GABRG1
diazepam anticonvulsant GABRG2
diazepam anticonvulsant GABRG3
diazepam anticonvulsant GABRP
diazepam anticonvulsant GABRQ
diazepam anticonvulsant GABRR1
diazepam anticonvulsant GABRR2
diazepam anticonvulsant GABRR3
NRM8499 for treatment of Alzheimer's disease APP
NRP290 analgesic OPRD1
NRP290 analgesic OPRK1
NRP290 analgesic OPRM1
triiodothyronine (T3) hormone replacement THRA
triiodothyronine (T3) hormone replacement THRB
NRX-5183 hematopoietic agent RARA
NS-304 antihypertensive agent PTGIR
NSD-644 analgesic, antidepressant SLC6A2
NSD-644 analgesic, antidepressant SLC6A3
NSD-644 analgesic, antidepressant SLC6A4
NSD-788 antidepressant SLC6A2
NSD-788 antidepressant SLC6A4
allopurinol for treatment of gout XDH
NV-52 antiinflammatory agent TBXAS1
glycopyrronium for treatment of chronic obstructive CHRM1
pulmonary disease (COPD)
tizanidine for treatment of skeletal muscular ADRA2A
spasticity
tizanidine for treatment of skeletal muscular ADRA2B
spasticity
tizanidine for treatment of skeletal muscular ADRA2C
spasticity
NXN-188 antimigraine agent HTR1B
NXN-188 antimigraine agent HTR1D
NXN-188 antimigraine agent NOS1
ondansetron antiemetic HTR3A
pacl*taxel antineoplastic agent BCL2
pacl*taxel antineoplastic agent TUBB1
obatoclax antineoplastic agent BCL2
betahistine antiobesity agent HRH1
betahistine antiobesity agent HRH3
obeticholic acid for treatment of non-alcoholic fatty NR1H4
liver disease (NAFLD), for treatment
of Primary Biliary Cirrhosis (PBC)
OC000459 antiallergy agent PD2R2
ocinaplon anxiolytic GABRA2
ocinaplon anxiolytic GABRA3
ocinaplon anxiolytic GABRA5
ocinaplon anxiolytic GABRA6
ocinaplon anxiolytic GABRB1
ocinaplon anxiolytic GABRB1
ocinaplon anxiolytic GABRB2
ocinaplon anxiolytic GABRB2
ocinaplon anxiolytic GABRB3
ocinaplon anxiolytic GABRD
ocinaplon anxiolytic GABRD
ocinaplon anxiolytic GABRE
ocinaplon anxiolytic GABRG1
ocinaplon anxiolytic GABRG2
ocinaplon anxiolytic GABRG3
ocinaplon anxiolytic GABRG3
ocinaplon anxiolytic GABRP
ocinaplon anxiolytic GABRQ
ocinaplon anxiolytic GABRR2
heparin antithrombotic F10
heparin antithrombotic F2
odanacatib antiosteoporotic agent CTSK
Oglemilast antiasthmatic agent PDE4A
Oglemilast antiasthmatic agent PDE4B
olanzapine antipsychotic agent ADRA1A
olanzapine antipsychotic agent ADRA1B
olanzapine antipsychotic agent ADRA2A
olanzapine antipsychotic agent ADRA2B
olanzapine antipsychotic agent ADRA2C
olanzapine antipsychotic agent CHRM1
olanzapine antipsychotic agent CHRM2
olanzapine antipsychotic agent CHRM3
olanzapine antipsychotic agent CHRM4
olanzapine antipsychotic agent CHRM5
olanzapine antipsychotic agent DRD1
olanzapine antipsychotic agent DRD2
olanzapine antipsychotic agent DRD3
olanzapine antipsychotic agent DRD4
olanzapine antipsychotic agent DRD5
olanzapine antipsychotic agent HRH1
olanzapine antipsychotic agent HTR1A
olanzapine antipsychotic agent HTR1B
olanzapine antipsychotic agent HTR1D
olanzapine antipsychotic agent HTR1E
olanzapine antipsychotic agent HTR2A
olanzapine antipsychotic agent HTR2C
olanzapine antipsychotic agent HTR3A
olanzapine antipsychotic agent HTR6
olanzapine antipsychotic agent HTR7
fluoxetine antidepressant, for treatment of SLC6A4
bipolar disorder
olanzapine antidepressant, for treatment of ADRA1A
bipolar disorder
olanzapine antidepressant, for treatment of ADRA1B
bipolar disorder
olanzapine antidepressant, for treatment of ADRA2A
bipolar disorder
olanzapine antidepressant, for treatment of ADRA2B
bipolar disorder
olanzapine antidepressant, for treatment of ADRA2C
bipolar disorder
olanzapine antidepressant, for treatment of CHRM1
bipolar disorder
olanzapine antidepressant, for treatment of CHRM2
bipolar disorder
olanzapine antidepressant, for treatment of CHRM3
bipolar disorder
olanzapine antidepressant, for treatment of CHRM4
bipolar disorder
olanzapine antidepressant, for treatment of CHRM5
bipolar disorder
olanzapine antidepressant, for treatment of DRD1
bipolar disorder
olanzapine antidepressant, for treatment of DRD2
bipolar disorder
olanzapine antidepressant, for treatment of DRD3
bipolar disorder
olanzapine antidepressant, for treatment of DRD4
bipolar disorder
olanzapine antidepressant, for treatment of DRD5
bipolar disorder
olanzapine antidepressant, for treatment of HRH1
bipolar disorder
olanzapine antidepressant, for treatment of HTR1A
bipolar disorder
olanzapine antidepressant, for treatment of HTR1B
bipolar disorder
olanzapine antidepressant, for treatment of HTR1D
bipolar disorder
olanzapine antidepressant, for treatment of HTR1E
bipolar disorder
olanzapine antidepressant, for treatment of HTR2A
bipolar disorder
olanzapine antidepressant, for treatment of HTR2C
bipolar disorder
olanzapine antidepressant, for treatment of HTR3A
bipolar disorder
olanzapine antidepressant, for treatment of HTR6
bipolar disorder
olanzapine antidepressant, for treatment of HTR7
bipolar disorder
olesoxime for treatment of motor neuron disease TSPO
olesoxime for treatment of motor neuron disease VDAC1
olesoxime for treatment of motor neuron disease VDAC2
olesoxime for treatment of motor neuron disease VDAC3
olmesartan antihypertensive agent AGTR1
olmesartan for treatment of glaucoma AGTR1
olopatadine antiallergy agent HRH1
omacetaxine mepesuccinate antineoplastic agent Ribosome A-site
ombrabulin antineoplastic agent TUBB1
omecamtiv mecarbil for treatment of heart failure Cardiac Mysoin
omeprazole Proton pump inhibitor ATP4A
omeprazole Proton pump inhibitor ATP4A
omeprazole Proton pump inhibitor ATP4A
omigapil antiparkinson agent, for treatment of GAPDA
amyotrophic lateral sclerosis (ALS)
omigapil antiparkinson agent, for treatment of SIAH1
amyotrophic lateral sclerosis (ALS)
amitriptyline analgesic HTR2A
amitriptyline analgesic HTR2A
amitriptyline analgesic SLC6A2
amitriptyline analgesic SLC6A2
amitriptyline analgesic SLC6A4
amitriptyline analgesic SLC6A4
ketoprofen NSAID PTGS1
ketoprofen NSAID PTGS1
ketoprofen NSAID PTGS2
ketoprofen NSAID PTGS2
oxymetazoline analgesic ADRA1A
oxymetazoline analgesic ADRA1A
oxymetazoline analgesic ADRA2A
oxymetazoline analgesic ADRA2A
rigosertib antineoplastic agent PIK3CA
rigosertib antineoplastic agent PIK3CB
rigosertib antineoplastic agent PIK3CD
rigosertib antineoplastic agent PLK1
pacl*taxel antineoplastic agent BCL2
pacl*taxel antineoplastic agent TUBB1
ondansetron antiemetic HTR3A
oprozomib antineoplastic agent PSMB1
oprozomib antineoplastic agent PSMB2
oprozomib antineoplastic agent PSMB5
oprozomib antineoplastic agent PSMD1
oprozomib antineoplastic agent PSMD2
pacl*taxel antineoplastic agent BCL2
pacl*taxel antineoplastic agent TUBB1
OPB-51602 antineoplastic agent STAT3
OPC-28326 vasodilator ADRA2B
OPC-28326 vasodilator ADRA2C
OPC-34712 antidepressant DRD2
OPC-34712 antidepressant HTR1A
OPC-34712 antidepressant HTR2A
OPC-34712 antidepressant HTR7
OPC-51803 for treatment of incontinence AVPR2
doxycyklin for treatment of dental disease MMP8
estrogen contraceptive, for treatment of female ESR1
sexual dysfunction
estrogen contraceptive, for treatment of female ESR2
sexual dysfunction
progestogen contraceptive, for treatment of female PGR
sexual dysfunction
estriol E3 for treatment of multiple sclerosis ESR1
estriol E3 for treatment of multiple sclerosis ESR2
pacl*taxel antineoplastic agent BCL2
pacl*taxel antineoplastic agent TUBB1
lidocaine anesthetic SCN10A
lidocaine anesthetic SCN5A
lidocaine anesthetic SCN9A
prilocaine anesthetic SCN5A
olanzapine antipsychotic agent ADRA1A
olanzapine antipsychotic agent ADRA1B
olanzapine antipsychotic agent ADRA2A
olanzapine antipsychotic agent ADRA2B
olanzapine antipsychotic agent ADRA2C
olanzapine antipsychotic agent CHRM1
olanzapine antipsychotic agent CHRM2
olanzapine antipsychotic agent CHRM3
olanzapine antipsychotic agent CHRM4
olanzapine antipsychotic agent CHRM5
olanzapine antipsychotic agent DRD1
olanzapine antipsychotic agent DRD2
olanzapine antipsychotic agent DRD3
olanzapine antipsychotic agent DRD4
olanzapine antipsychotic agent DRD5
olanzapine antipsychotic agent HRH1
olanzapine antipsychotic agent HTR1A
olanzapine antipsychotic agent HTR1B
olanzapine antipsychotic agent HTR1D
olanzapine antipsychotic agent HTR1E
olanzapine antipsychotic agent HTR2A
olanzapine antipsychotic agent HTR2C
olanzapine antipsychotic agent HTR3A
olanzapine antipsychotic agent HTR6
olanzapine antipsychotic agent HTR7
zonisamide antipsychotic agent CACNA1G
zonisamide antipsychotic agent CACNA1H
zonisamide antipsychotic agent CACNA1I
zonisamide antipsychotic agent SCN11A
zonisamide antipsychotic agent SCN1A
zonisamide antipsychotic agent SCN1B
zonisamide antipsychotic agent SCN2A
zonisamide antipsychotic agent SCN2B
zonisamide antipsychotic agent SCN3A
zonisamide antipsychotic agent SCN3B
zonisamide antipsychotic agent SCN4A
zonisamide antipsychotic agent SCN4B
zonisamide antipsychotic agent SCN5A
zonisamide antipsychotic agent SCN9A
orlistat antiobesity agent FASN
orlistat antiobesity agent LPL
orlistat antiobesity agent PNLIP
ortataxel antineoplastic agent BCL2
ortataxel antineoplastic agent TUBB1
orteronel antineoplastic agent CYP17A1
OSI-027 antineoplastic agent MTOR
OSI-461 antineoplastic agent PDE5A
OSI-7904L antineoplastic agent TYMS
OSI-906 antineoplastic agent IGF1R
OSI-930 antineoplastic agent KDR
ospemifene for treatment of postmenopausal ESR1
vagin*l atrophy
ospemifene for treatment of postmenopausal ESR2
vagin*l atrophy
enobosarm hormone replacement AR
OT-730 for treatment of glaucoma ADRB1
OT-730 for treatment of glaucoma ADRB2
otamixaban antithrombotic F10
dexamethasone antiinflammatory NR3C1
agent, glucocorticoid, for treatment of
Meniere's disease
famotidine acid reducer HRH2
omeprazole Proton pump inhibitor ATP4A
zolpidem hypnotic GABRA1
zolpidem hypnotic GABRA2
zolpidem hypnotic GABRA3
OX914 antiallergy agent PDE4A
OX914 antiallergy agent PDE4B
oxandrolone anabolic agent AR
oxcarbazepine anticonvulsant SCN5A
combretastatin A1 di-phosphate antineoplastic agent TUBB1
oxycodone analgesic OPRD1
oxycodone analgesic OPRK1
oxycodone analgesic OPRM1
niacin substance abuse deterrant GPR109A
niacin substance abuse deterrant GPR109B
niacin substance abuse deterrant NNMT
niacin substance abuse deterrant QPRT
oxycodone analgesic OPRD1
oxycodone analgesic OPRK1
oxycodone analgesic OPRM1
oxycodone analgesic OPRD1
oxycodone analgesic OPRK1
oxycodone analgesic OPRM1
oxymorphone analgesic OPRD1
oxymorphone analgesic OPRM1
P-552 for treatment of dry mouth ACCN2
P-552 for treatment of dry mouth ACCN3
P-552 for treatment of dry mouth ACCN4
P-552 for treatment of dry mouth ASIC2
P-552 for treatment of dry mouth SCNN1A
P-552 for treatment of dry mouth SCNN1B
P-552 for treatment of dry mouth SCNN1D
P-552 for treatment of dry mouth SCNN1G
acetylsalicylic acid NSAID PTGS1
acetylsalicylic acid NSAID PTGS2
omeprazole Proton pump inhibitor ATP4A
pacl*taxel antineoplastic agent BCL2
pacl*taxel antineoplastic agent TUBB1
pacl*taxel antineoplastic agent BCL2
pacl*taxel antineoplastic agent TUBB1
pacl*taxel for treatment of peripheral arterial BCL2
disease (PAD)
pacl*taxel for treatment of peripheral arterial TUBB1
disease (PAD)
pagoclone for treatment of premature GABRA2
ejacul*tion, for treatment of
persistant stuttering
pagoclone for treatment of premature GABRB2
ejacul*tion, for treatment of
persistant stuttering
paliperidone antipsychotic agent DRD2
paliperidone antipsychotic agent HTR2A
Palomid 529 for treatment of age-related macular MTOR
degeneration
Palonosetron antiemetic HTR3A
Panobinostat antineoplastic agent HDAC1
Panobinostat antineoplastic agent HDAC10
Panobinostat antineoplastic agent HDAC11
Panobinostat antineoplastic agent HDAC2
Panobinostat antineoplastic agent HDAC3
Panobinostat antineoplastic agent HDAC4
Panobinostat antineoplastic agent HDAC5
Panobinostat antineoplastic agent HDAC6
Panobinostat antineoplastic agent HDAC7A
Panobinostat antineoplastic agent HDAC8
Panobinostat antineoplastic agent HDAC9
pantoprazole Proton pump inhibitor ATP4A
pardoprunox antiparkinson agent ADRA1A
pardoprunox antiparkinson agent ADRA2A
pardoprunox antiparkinson agent DRD2
pardoprunox antiparkinson agent DRD3
pardoprunox antiparkinson agent DRD4
pardoprunox antiparkinson agent HTR1A
pardoprunox antiparkinson agent HTR7
parecoxib antiinflammatory agent, NSAID PTGS2
paricalcitol for treatment of hyperparathyroidism VDR
paroxetine antidepressant SLC6A4
Pazopanib antineoplastic agent FLT1
Pazopanib antineoplastic agent FLT4
Pazopanib antineoplastic agent KDR
bleomycin antineoplastic agent LIG1
CRA-024781 antineoplastic agent HDAC1
CRA-024781 antineoplastic agent HDAC10
CRA-024781 antineoplastic agent HDAC2
CRA-024781 antineoplastic agent HDAC3
CRA-024781 antineoplastic agent HDAC6
ibrutinib antineoplastic agent BTK
PD-6735 hypnotic MTNR1A
PD-6735 hypnotic MTNR1B
10-propargyl-10- antineoplastic agent DHFR
deazaaminopterin
PEG-camptothecin antineoplastic agent TOP1
pentosan polysulfate for symptomatic treatment of bladder FGF1
pain or discomfort associated with
interstitial cystitis
pentosan polysulfate for symptomatic treatment of bladder FGF2
pain or discomfort associated with
interstitial cystitis
pentosan polysulfate for symptomatic treatment of bladder FGF4
pain or discomfort associated with
interstitial cystitis
pentostatin antineoplastic agent ADA
pentoxifylline for treatment of amyotrophic lateral ADORA1
sclerosis (ALS)
pentoxifylline for treatment of amyotrophic lateral ADORA2B
sclerosis (ALS)
pentoxifylline for treatment of amyotrophic lateral PDE4A
sclerosis (ALS)
pentoxifylline for treatment of amyotrophic lateral PDE4B
sclerosis (ALS)
pentoxifylline for treatment of amyotrophic lateral PDE5A
sclerosis (ALS)
ingenol Mebutate for treatment of actinic PKN1
keratosis, antineoplastic agent
ingenol Mebutate for treatment of actinic PKN2
keratosis, antineoplastic agent
ingenol Mebutate for treatment of actinic PRKCA
keratosis, antineoplastic agent
ingenol Mebutate for treatment of actinic PRKCB1
keratosis, antineoplastic agent
ingenol Mebutate for treatment of actinic PRKCD
keratosis, antineoplastic agent
ingenol Mebutate for treatment of actinic PRKCE
keratosis, antineoplastic agent
ingenol Mebutate for treatment of actinic PRKCG
keratosis, antineoplastic agent
ingenol Mebutate for treatment of actinic PRKCH
keratosis, antineoplastic agent
ingenol Mebutate for treatment of actinic PRKCI
keratosis, antineoplastic agent
ingenol Mebutate for treatment of actinic PRKCQ
keratosis, antineoplastic agent
ingenol Mebutate for treatment of actinic PRKCZ
keratosis, antineoplastic agent
irinotecan antineoplastic agent TOP1
irinotecan antineoplastic agent TOP1MT
perifosine antineoplastic agent AKT1
perifosine antineoplastic agent AKT2
perifosine antineoplastic agent AKT3
PF-00610355 bronchodilator ADRB2
PF-04554878 antineoplastic agent PTK2
Dacomitinib antineoplastic agent EGFR
Dacomitinib antineoplastic agent ERBB2
Dacomitinib antineoplastic agent ERBB4
PG-490-88 antineoplastic agent NFKB1
PG-490-88 antineoplastic agent NFKB2
PG545 antineoplastic agent HPSE
PH-797804 antiinflammatory agent, DMARD MAPK11
PH-797804 antiinflammatory agent, DMARD MAPK12
PH-797804 antiinflammatory agent, DMARD MAPK13
PH-797804 antiinflammatory agent, DMARD MAPK14
phenoxodiol antineoplastic agent SPHK1
phenoxodiol antineoplastic agent SPHK2
phenserine for treatment of Alzheimer's disease ACHE
physostigmine for treatment of dry mouth ACHE
Pimavanserin antiparkinson agent HTR2A
pimecrolimus antiinflammatory agent MTOR
pioglitazone antidiabetic PPARG
metformin antidiabetic PRKAB1
pioglitazone antidiabetic PPARG
pirfenidone for treatment of fibrotic conditions MAPK11
pirfenidone for treatment of fibrotic conditions MAPK12
pirfenidone for treatment of fibrotic conditions MAPK13
pirfenidone for treatment of fibrotic conditions MAPK14
pitavastatin anticholesterolaemic agent HMGCR
PL37 analgesic, neuropathic pain ANPEP
PL37 analgesic, neuropathic pain MME
clopidogrel antithrombotic P2RY12
PLK-1 inhibitor antineoplastic agent PLK1
vemurafenib antineoplastic agent BRAF
PMI-001 antiinflammatory agent, DMARD NR3C1
naproxen NSAID PTGS1
naproxen NSAID PTGS2
omeprazole Proton pump inhibitor ATP4A
carmustine antineoplastic agent GSR
ponatinib antineoplastic agent ABL1
ponatinib antineoplastic agent SRC
ponesimod antiinflammatory agent, for treatment S1PR1
of multiple sclerosis
Posiphen for treatment of Alzheimer's disease APP
Posiphen for treatment of Alzheimer's disease BACE1
Posiphen for treatment of Alzheimer's disease BACE2
pozanicline for treatment of Alzheimer's disease CHRNA4
pozanicline for treatment of Alzheimer's disease CHRNB2
PPC-5650 analgesic ACCN2
PPI-2458 antineoplastic agent METAP2
PR-15 antithrombotic GP6
prasterone hormone supplement for increasing AR
bone mineral density in patients with
systemic lupus erythematosus
prasugrel antithrombotic P2RY12
fenofibrate anticholesterolaemic agent PPARA
pravastatin anticholesterolaemic agent HMGCR
prednisolone antiinflammatory NR3C1
agent, corticosteroid
prednisolone antiinflammatory NR3C1
agent, corticosteroid
pregabalin analgesic, neuropathic pain, for CACNA1A
treatment of restlegs legs syndrome
preladenant antiparkinson agent ADORA2A
pridopidine for treatment of Huntington's disease DRD2
desvenlafaxine for treatment of menopausal SLC6A2
symptoms, antidepressant
desvenlafaxine for treatment of menopausal SLC6A4
symptoms, antidepressant
diclofenac NSAID PTGS1
diclofenac NSAID PTGS2
telapristone for treatment of uterin fibroids and PGR
endometriosis
progesterone for reducing the risk of pre-term birth PGR
for women with short cervix a mid-
pregnancy
testosterone hormone replacement AR
eltrombopag thrombopoietic MPL
propafenone antiarrythmic agent KCNH2
propafenone antiarrythmic agent SCN5A
propionyl-L-carnitine for treatment of intermittent CPT1A
claudication
propionyl-L-carnitine for treatment of intermittent CPT2
claudication
propionyl-L-carnitine for treatment of intermittent CRAT
claudication
propionyl-L-carnitine for treatment of intermittent CROT
claudication
propionyl-L-carnitine for treatment of intermittent SLC22A4
claudication
propionyl-L-carnitine for treatment of intermittent SLC22A5
claudication
propionyl-L-carnitine for treatment of intermittent SLC25A20
claudication
propionyl-L-carnitine for treatment of intermittent SLC25A29
claudication
propofol sedative GABRB2
propofol sedative GABRB3
propofol sedative SCN2A
propofol sedative SCN4A
propofol sedative GABRB2
propofol sedative GABRB3
propofol sedative SCN2A
propofol sedative SCN4A
OPC-14523 antidepressant HTR1A
OPC-14523 antidepressant PGRMC1
OPC-14523 antidepressant SIGMAR1
OPC-14523 antidepressant SLC6A4
PRT062607 antiinflammatory agent SYK
prucalopride motilitant HTR4
PRX-00023 antidepressant, anxiolytic HTR1A
PRX-07034 antiobesity agent, nootropic HTR6
PRX-08066 antihypertensive agent HTR2B
PRX-3140 for treatment of Alzheimer's disease HTR4
PS433540 antihypertensive agent AGTR1
PS433540 antihypertensive agent AGTR2
PS433540 antihypertensive agent EDNRA
lidocaine for treatment of premature EGFR
ejacul*tion
lidocaine for treatment of premature SCN10A
ejacul*tion
lidocaine for treatment of premature SCN5A
ejacul*tion
prilocaine for treatment of premature SCN5A
ejacul*tion
phenylephrine for treatment of incontinence ADRA1A
phenylephrine for treatment of incontinence ADRA1B
phenylephrine for treatment of incontinence ADRA1D
PSD-506 for treatment of overactive bladder CHRM2
PSD-506 for treatment of overactive bladder CHRM3
PSN357 antidiabetic PYGB
PSN357 antidiabetic PYGL
PSN357 antidiabetic PYGM
PSN602 antiobesity agent HTR1A
PSN602 antiobesity agent SLC6A2
PSN602 antiobesity agent SLC6A3
PSN602 antiobesity agent SLC6A4
PSN821 antidiabetic GPR119
glycopyrrolate for treatment of chronic obstructive CHRM1
pulmonary disorder (COPD)
formoterol for treatment of chronic obstructive ADRB2
pulmonary disorder (COPD)
glycopyrrolate for treatment of chronic obstructive CHRM1
pulmonary disorder (COPD)
formoterol for treatment of chronic obstructive ADRB2
pulmonary disorder (COPD)
PTC299 antineoplastic agent FLT1
PTC299 antineoplastic agent FLT4
PTC299 antineoplastic agent KDR
naltrexone analgesic OPRD1
naltrexone analgesic OPRD1
naltrexone analgesic OPRK1
naltrexone analgesic OPRK1
naltrexone analgesic OPRM1
naltrexone analgesic OPRM1
naltrexone analgesic SIGMAR1
tramadol analgesic HTR2C
tramadol analgesic OPRK1
tramadol analgesic OPRK1
tramadol analgesic OPRM1
tramadol analgesic OPRM1
tramadol analgesic SLC6A2
tramadol analgesic SLC6A2
tramadol analgesic SLC6A4
acetaminophen analgesic PTGS1
acetaminophen analgesic PTGS1
acetaminophen analgesic PTGS2
acetaminophen analgesic PTGS2
hydrocodone analgesic OPRD1
hydrocodone analgesic OPRD1
hydrocodone analgesic OPRM1
hydrocodone analgesic OPRM1
naltrexone analgesic OPRD1
naltrexone analgesic OPRD1
naltrexone analgesic OPRK1
naltrexone analgesic OPRK1
naltrexone analgesic OPRM1
naltrexone analgesic OPRM1
naltrexone analgesic SIGMAR1
naltrexone analgesic SIGMAR1
naltrexone analgesic OPRD1
naltrexone analgesic OPRK1
naltrexone analgesic OPRM1
oxycodone analgesic OPRD1
oxycodone analgesic OPRK1
oxycodone analgesic OPRM1
naltrexone analgesic OPRD1
naltrexone analgesic OPRK1
naltrexone analgesic OPRM1
Pumosetrag motilitant HTR3A
Pumosetrag motilitant HTR3B
Pumosetrag motilitant HTR3C
Pumosetrag motilitant HTR3D
Pumosetrag motilitant HTR3E
PW2101 antihypertensive agent ADRB2
PX-12 antineoplastic agent TXN
PX-478 antineoplastic agent HIF1A
belinostat antineoplastic agent HDAC1
belinostat antineoplastic agent HDAC10
belinostat antineoplastic agent HDAC11
belinostat antineoplastic agent HDAC2
belinostat antineoplastic agent HDAC3
belinostat antineoplastic agent HDAC4
belinostat antineoplastic agent HDAC5
belinostat antineoplastic agent HDAC6
belinostat antineoplastic agent HDAC7A
belinostat antineoplastic agent HDAC8
belinostat antineoplastic agent HDAC9
PYM50028 antiparkinson agent GFRA1
PYM50028 antiparkinson agent NGFR
PYM50028 antiparkinson agent NTRK1
PYM50028 antiparkinson agent NTRK2
quinapril antihypertensive agent ACE
glycopyrronium bromide for treatment of chronic obstructive ADRB2
pulmonary disorder (COPD)
indacaterol for treatment of chronic obstructive CHRM1
pulmonary disorder (COPD)
R112 antiallergy agent FCER1A
R112 antiallergy agent FCER1G
R112 antiallergy agent MS4A2
R343 antiallergy agent SYK
R348 antiinflammatory agent JAK3
R667 for treatment of emphysema RARA
R667 for treatment of emphysema RARB
R667 for treatment of emphysema RARG
R763 antineoplastic agent AURKA
R763 antineoplastic agent AURKB
R763 antineoplastic agent AURKC
RAD1901 for treatment of postmenopausal ESR1
symptoms
raltitrexed antineoplastic agent TYMS
ramelteon for treatment of insomnia MTNR1A
ramelteon for treatment of insomnia MTNR1B
ranolazine antiallergy agent SCN5A
ranolazine antiallergy agent SCN9A
ranirestat for treatment of diabetic neuropathy AKR1B1
ranitidine antiulcer agent HRH2
rasagiline antiparkinson agent MAOB
RC-8800 for improving the antiproliferative CYP46A1
and apoptotic properties of vitamin
D3
RDEA119 antineoplastic agent MAPK1
RDEA119 antineoplastic agent MAPK3
regadenoson diagnostic agent ADORA2A
regorafenib antineoplastic agent KDR
regorafenib antineoplastic agent TEK
relacatib antiosteoporotic agent CTSK
eletriptan antimigraine agent HTR1D
remifentanil analgesic OPRM1
Nalbuphine analgesic OPRD1
Nalbuphine analgesic OPRK1
Nalbuphine analgesic OPRM1
naloxone analgesic OPRD1
naloxone analgesic OPRK1
naloxone analgesic OPRM1
renzapride for treatment of irritable bowel HTR2A
syndrome
renzapride for treatment of irritable bowel HTR2B
syndrome
renzapride for treatment of irritable bowel HTR2C
syndrome
renzapride for treatment of irritable bowel HTR3A
syndrome
renzapride for treatment of irritable bowel HTR4
syndrome
repaglinide antidiabetic ABCC8
ropinirol antiparkinson agent DRD2
ropinirol antiparkinson agent DRD3
resiniferatoxin for treatment of interstitial TRPV1
cystitis, antiincontinence agent
Resminostat antineoplastic agent HDAC1
Resminostat antineoplastic agent HDAC10
Resminostat antineoplastic agent HDAC11
Resminostat antineoplastic agent HDAC2
Resminostat antineoplastic agent HDAC3
Resminostat antineoplastic agent HDAC4
Resminostat antineoplastic agent HDAC5
Resminostat antineoplastic agent HDAC6
Resminostat antineoplastic agent HDAC7A
Resminostat antineoplastic agent HDAC8
Resminostat antineoplastic agent HDAC9
Resveratrol for treatment of herpes simplex virus PDE4B
1
Resveratrol for treatment of herpes simplex virus PDE4D
1
retigabine anticonvulsant KCNQ1
retigabine anticonvulsant KCNQ2
retigabine anticonvulsant KCNQ3
retigabine anticonvulsant KCNQ4
retigabine anticonvulsant KCNQ5
rEV131 antiallergy agent HRH4
lenalidomide antineoplastic agent TNFSF11
RG2833 for treatment of Friedrich's ataxia HDAC3
RG3039 for treatment of spinal muscular DCPS
atrophy
Ridaforolimus antineoplastic agent MTOR
riluzole for treatment of ALS SCN5A
riluzole for treatment of ALS SLC7A11
rimcazole antineoplastic agent SIGMAR1
Rimonabant antiobesity agent CNR1
riociguat antihypertensive agent GUCY1A2
riociguat antihypertensive agent GUCY1A3
riociguat antihypertensive agent GUCY1B2
riociguat antihypertensive agent GUCY1B3
risedronate antiosteoporotic agent FDPS
Risperdal antipsychotic agent DRD2
Risperdal antipsychotic agent HTR2A
rivaroxaban antithrombotic F10
rivastigmine for treatment of Alzheimer's disease ACHE
rivastigmine for treatment of Alzheimer's disease BCHE
Rob 803 antiinflammatory agent, DMARD unknown
rocuronium muscle relaxant CHRM2
rocuronium muscle relaxant CHRNA2
rocuronium muscle relaxant HTR3A
rofecoxib NSAID PTGS2
roflumilast for treatment of chronic obstructive PDE4A
pulmonary disorder (COPD)
roflumilast for treatment of chronic obstructive PDE4B
pulmonary disorder (COPD)
rolofylline for treatment of congestive heart ADORA1
failure
ronacaleret antiiosteoporotic agent CASR
ropivacaine anestethic SCN10A
glimepiride antidiabetic ABCC8
glimepiride antidiabetic KCNJ1
glimepiride antidiabetic KCNJ11
rosiglitazone antidiabetic PPARG
metformin antidiabetic PRKAB1
rosiglitazone antidiabetic PPARG
rosiglitazone for treatment of Alzheimer's PPARG
disease, antidiabetic
ketorolac antimigraine agent PTGS1
ketorolac antimigraine agent PTGS2
bromovinyl deoxyuridine antineoplastic agent POLA1
RPC1063 for treatment of multiple sclerosis S1PR1
RPL-554 bronchodilator PDE3A
RPL-554 bronchodilator PDE3B
RPL-554 bronchodilator PDE4A
RPL-554 bronchodilator PDE4B
RTA 744 antineoplastic agent TOP2A
RTA 744 antineoplastic agent TOP2B
rubitecan antineoplastic agent TOP1
ruboxistaurin for treatment of diabetic neuropathy PRKCB1
RVX-208 antiatherosclerotic agent APOA1
gimestat antineoplastic agent DPYD
tegafur antineoplastic agent TYMS
pacl*taxel antineoplastic agent BCL2
pacl*taxel antineoplastic agent TUBB1
SA4503 antidepressant, neuroprotectant SIGMAR1
Safinamide antiparkinson agent CACNA1B
Safinamide antiparkinson agent CACNA2D1
Safinamide antiparkinson agent CACNA2D2
Safinamide antiparkinson agent CACNB3
Safinamide antiparkinson agent CACNB4
Safinamide antiparkinson agent MAOB
Safinamide antiparkinson agent SCN11A
Safinamide antiparkinson agent SCN11A
Safinamide antiparkinson agent SCN1A
Safinamide antiparkinson agent SCN2A
Safinamide antiparkinson agent SCN3A
Safinamide antiparkinson agent SCN4A
Safinamide antiparkinson agent SCN5A
Safinamide antiparkinson agent SCN7A
Safinamide antiparkinson agent SCN8A
Safinamide antiparkinson agent SCN9A
tetrahydrobiopterin for treatment of phenolketonuria NOS3
(PKU)
tetrahydrobiopterin for treatment of phenolketonuria PAH
(PKU)
tetrahydrobiopterin for treatment of phenolketonuria TH
(PKU)
tetrahydrobiopterin for treatment of phenolketonuria TPH1
(PKU)
SAR 1118 antiinflammatory agent ICAM1
SAR 1118 antiinflammatory agent ITGAL
SAR 1118 antiinflammatory agent ITGB2
saredutant antidepressant, anxiolytic TACR2
nabilone analgesic, neuropathic pain, for CNR2
treatment of restlegs legs syndrome
nabilone analgesic, neuropathic pain, for CNR2
treatment of restlegs legs syndrome
Saxagliptin antidiabetic DPP4
SB1518 antineoplastic agent JAK2
SB-559448 thrombopoietic agent MPL
SB-681323 antiinflammatory agent, DMARD MAPK14
firategrast antiinflammatory agent ITGA4
firategrast antiinflammatory agent ITGB1
pracinostat antineoplastic agent HDAC1
pracinostat antineoplastic agent HDAC10
pracinostat antineoplastic agent HDAC11
pracinostat antineoplastic agent HDAC2
pracinostat antineoplastic agent HDAC3
pracinostat antineoplastic agent HDAC4
pracinostat antineoplastic agent HDAC5
pracinostat antineoplastic agent HDAC6
pracinostat antineoplastic agent HDAC7A
pracinostat antineoplastic agent HDAC8
pracinostat antineoplastic agent HDAC9
SCH-527123 for treatment of chronic obstructive CXCR1
pulmonary disorder (COPD)
SCH-527123 for treatment of chronic obstructive CXCR2
pulmonary disorder (COPD)
talmapimod antiinflammatory agent, DMARD MAPK14
SCY-635 for treatment of hepatitis C PP1A
SCY-635 for treatment of hepatitis C PP1D
scyllo-inositol for treatment of Alzheimer's disease APP
R-etodolac antineoplastic agent RXRA
selegiline antidepressant MAOB
selegiline antiparkinson agent MAOB
seletracetam anticonvulsant SV2A
selexipag antihypertensive agent PTGIR
seliciclib antineoplastic agent CDK2
seliciclib antineoplastic agent CDK7
seliciclib antineoplastic agent CDK9
maraviroc antiviral agent, HIV CCR5
eszopiclone anxiolytic GABRA1
clavulanic acid antidepressant FOLH1
SERTINDOLE antipsychotic agent ADRA1A
SERTINDOLE antipsychotic agent ADRA1B
SERTINDOLE antipsychotic agent ADRA1D
SERTINDOLE antipsychotic agent DRD2
SERTINDOLE antipsychotic agent HTR2A
SERTINDOLE antipsychotic agent HTR2C
SERTINDOLE antipsychotic agent HTR6
SERTINDOLE antipsychotic agent KCNH2
salmeterol bronchodilator ADRB2
Quetiapine antipsychotic agent, antidepressant DRD2
Quetiapine antipsychotic agent, antidepressant HTR2A
Quetiapine antipsychotic agent, antidepressant HTR2B
Quetiapine antipsychotic agent, antidepressant HTR2C
Quetiapine antipsychotic agent, antidepressant HTR2C
SF1126 antineoplastic agent MTOR
SF1126 antineoplastic agent PIK3C3
SF1126 antineoplastic agent PIK3CA
SF1126 antineoplastic agent PIK3CA
SF1126 antineoplastic agent PIK3CB
SF1126 antineoplastic agent PIK3CD
SF1126 antineoplastic agent PIK3CD
SF1126 antineoplastic agent PIK3CG
SF1126 antineoplastic agent PIK3CG
SF1126 antineoplastic agent PRKDC
SGI-1776 antineoplastic agent PIM1
SGI-1776 antineoplastic agent PIM2
SGI-1776 antineoplastic agent PIM3
beclomethasone antiinflammatory NR3C1
agent, glucocorticoid
SGX523 antineoplastic agent MET
sibutramine appetite suppressant SLC6A2
sibutramine appetite suppressant SLC6A3
sibutramine appetite suppressant SLC6A4
sildenafil for treatment of erectile PDE5A
dysfucntion, antihypertensive agent
doxepin hypnotic CHRM1
doxepin hypnotic CHRM2
doxepin hypnotic CHRM3
doxepin hypnotic CHRM4
doxepin hypnotic CHRM5
doxepin hypnotic HRH1
doxepin hypnotic HRH2
doxepin hypnotic HTR2A
doxepin hypnotic HTR2B
doxepin hypnotic HTR2C
doxepin hypnotic SLC6A2
doxepin hypnotic SLC6A4
Silodosin for treatment of BPH-related urinary ADRA1A
symptoms
sirolimus for treatment of wet age-related FKBP1A
macular degeneration
sirolimus for treatment of wet age-related MTOR
macular degeneration
sirolimus immunosuppressant FKBP1A
sirolimus immunosuppressant MTOR
Sitagliptin antidiabetic DPP4
sivelestat for treatment of acute lung injury ELA2
associated with systemic
inflammatory response syndrome
(SIRS)
zaleplon hypnotic GABRA1
zaleplon hypnotic TSPO
fluticasone antiinflammatory NR3C1
agent, glucocorticoid
formoterol bronchodilator ADRB2
amphetamine for treatment of cognitive SLC18A2
dysfunction, for treatment of ADHD
amphetamine for treatment of cognitive SLC6A3
dysfunction, for treatment of ADHD
amphetamine for treatment of cognitive TAAR1
dysfunction, for treatment of ADHD
dextroamphetamine for treatment of ADHD SLC18A2
dextroamphetamine for treatment of ADHD SLC6A2
dextroamphetamine for treatment of ADHD SLC6A3
SLx-2101 antihypertensive agent, for treatment PDE5A
of erectile dysfunction
SLx-4090 antidyslipidaemic agent MTTP
SNS-032 antineoplastic agent CDK2
SNS-032 antineoplastic agent CDK7
SNS-032 antineoplastic agent CDK9
SNS-314 antineoplastic agent AURKA
SNS-314 antineoplastic agent AURKB
SNX-5422 antineoplastic agent HSP90AA1
SNX-5422 antineoplastic agent HSP90AB1
sobetirome antihypecholesterolemic agent THRB
gamma hydroxybutyric acid hypnotic GABBR1
gamma hydroxybutyric acid hypnotic GABBR2
gamma hydroxybutyric acid hypnotic SLC5A2
stibogluconate antineoplastic agent PTPN11
levonorgestrel contraceptive ESR1
levonorgestrel contraceptive PGR
levonorgestrel contraceptive SRD5A1
solabegron antidiabetic, for treatment of irritable ADRB3
bowel syndrome, antiincontinence
agent
Solifenacin for treatment of incontinence CHRM1
Solifenacin for treatment of incontinence CHRM2
Solifenacin for treatment of incontinence CHRM3
Solifenacin for treatment of incontinence CHRM4
Solifenacin for treatment of incontinence CHRM5
SOU-001 for treatment of incontinence ADRA1A
SOU-001 for treatment of incontinence ADRA1B
SOU-001 for treatment of incontinence ADRA1D
SOU-003 for treatment of incontinence AVPR2
doxorubicin antineoplastic agent TOP2A
carbamazepine for treatment of bipolar disorder SCN5A
mesalamine for treatment of ulcerative colitis ALOX5
mesalamine for treatment of ulcerative colitis CHUK
mesalamine for treatment of ulcerative colitis IKBKB
mesalamine for treatment of ulcerative colitis PPARG
mesalamine for treatment of ulcerative colitis PTGS1
mesalamine for treatment of ulcerative colitis PTGS2
allopurinol antiuricemic agent XDH
SPP676 antihypertensive agent REN
Resveratrol antidiabetic, antineoplastic agent PDE4B
Resveratrol antidiabetic, antineoplastic agent PDE4D
ganetespib antineoplastic agent HSP90AA1
ganetespib antineoplastic agent HSP90AB1
stannsoporfin for prevention of hyperbilirubinemia HMOX1
stannsoporfin for prevention of hyperbilirubinemia HMOX2
nateglinide antidiabetic ABCC8
morphine analgesic OPRK1
morphine analgesic OPRK1
morphine analgesic OPRK1
strontium ranelate antiosteoporotic agent CASR
STX107 for treatment of Fragile X symptoms GRM5
sucralfate antiulcer agent PGA3
sufentanil analgesic OPRD1
sufentanil analgesic OPRK1
sufentanil analgesic OPRM1
sufentanil analgesic OPRD1
sufentanil analgesic OPRK1
sufentanil analgesic OPRM1
sulfasalazine antiinflammatory agent, DMARD ACAT1
sulfasalazine antiinflammatory agent, DMARD PPARG
sulfasalazine antiinflammatory agent, DMARD PTGS1
sulfasalazine antiinflammatory agent, DMARD PTGS2
sulodexide for treatment of diabetic nephropathy SERPINC1
sulodexide for treatment of diabetic nephropathy SERPIND1
Sumatriptan antimigraine agent HTR1A
Sumatriptan antimigraine agent HTR1B
Sumatriptan antimigraine agent HTR1D
Sumatriptan antimigraine agent HTR1F
Sumatriptan antimigraine agent HTR1A
Sumatriptan antimigraine agent HTR1B
Sumatriptan antimigraine agent HTR1D
Sumatriptan antimigraine agent HTR1F
Sumatriptan antimigraine agent HTR1A
Sumatriptan antimigraine agent HTR1B
Sumatriptan antimigraine agent HTR1D
Sumatriptan antimigraine agent HTR1F
surinabant smoking-cessation agent CNR1
latanoprost for treatment of glaucoma PTGFR
sunitinib antineoplastic agent FLT1
sunitinib antineoplastic agent FLT3
sunitinib antineoplastic agent FLT4
sunitinib antineoplastic agent KDR
sunitinib antineoplastic agent KIT
sunitinib antineoplastic agent PDGFRA
sunitinib antineoplastic agent PDGFRB
sunitinib antineoplastic agent RET
SUVN-502 for treatment of Alzheimer's disease HTR6
SVT-40776 for treatment of incontinence CHRM3
tozadenant antiparkinson agent ADORA2A
nitisinone antiparkinson agent HPD
T-5224 antiinflammatory agent, DMARD JUN
T-62 analgesic ADORA1
tacrolimus immunosuppressant FKBP1A
tacrolimus immunosuppressant FKBP1A
TAFA-93 immunosuppressant FRAP1
TAK-242 for treatment of sepsis TLR4
dexlansoprazole Proton pump inhibitor ATP4A
TAK-442 antithrombotic F10
Talabostat for treatment of neutropenia CSF3
talampanel antiparkinson agent, antineoplastic GRIA1
agent
talampanel antiparkinson agent, antineoplastic GRIA2
agent
talampanel antiparkinson agent, antineoplastic GRIA3
agent
talampanel antiparkinson agent, antineoplastic GRIA4
agent
talarozole antipsoriatic agent, for treatment of CYP26A1
acne
talarozole antipsoriatic agent, for treatment of CYP26B1
acne
talarozole antipsoriatic agent, for treatment of CYP26C1
acne
talnetant antipsychotic agent TACR3
talotrexin antineoplastic agent DHFR
Tamibarotene antineoplastic agent RARA
Tamibarotene antineoplastic agent RARB
tamsulosin for treatment of urinary symptoms ADRA1A
associated with BPH
tamsulosin for treatment of urinary symptoms ADRA1B
associated with BPH
tamsulosin for treatment of urinary symptoms ADRA1D
associated with BPH
tandutinib antineoplastic agent FLT3
Tanespimycin antineoplastic agent HSP90AA1
Tanespimycin antineoplastic agent HSP90AB1
tapentadol analgesic OPRM1
tapentadol analgesic SLC6A2
tapentadol analgesic, opioid MOR
Taranabant antiobesity agent, smoking-cessation CNR1
agent
erlotinib antineoplastic agent EGFR
tariquidar adjuvant to chemotherapy ABCB1
TAS-108 antineoplastic agent ESR1
TAS-108 antineoplastic agent ESR2
tasimelteon hypnotic MTNR1A
tasimelteon hypnotic MTNR1B
Tasocitinib antiinflammatory agent, DMARD JAK3
tazarotene antipsoriatic agent, for treatment of RARA
acne
tazarotene antipsoriatic agent, for treatment of RARB
acne
tazarotene antipsoriatic agent, for treatment of RARG
acne
tazarotene antipsoriatic agent, for treatment of RXRB
acne
TBR-652 antiviral agent, HIV CCR5
ispronicline nootropic CHRNA4
ispronicline nootropic CHRNB2
TC-2403-12 for treatment of ulcerative colitis CHRNA4
TC-2403-12 for treatment of ulcerative colitis CHRNB2
TC-2696 analgesic CHRNA4
TC-2696 analgesic CHRNB2
TC-5214 antidepressant CHRNA4
TC-5214 antidepressant CHRNB2
TC-5619 neuroprotectant CHRNA7
TC-6499 analgesic, neuropathic pain CHRNA4
TC-6499 analgesic, neuropathic pain CHRNB2
TC-6987 antiasthmatic agent, antidiabetic CHRNA7
TD-1211 for treatment of opioid-induced OPRM1
gastrointestinal side-effects
tecadenoson antiarrhytmic agent ADORA1
tecarfarin antithrombotic VKORC1
tegaserod motilitant HTR4
telatinib antineoplastic agent FLT1
telatinib antineoplastic agent FLT4
telatinib antineoplastic agent KDR
telatinib antineoplastic agent PDGFRA
telatinib antineoplastic agent PDGFRB
telmisartan antihypertensive agent AGTR1
temsirolimus antineoplastic agent FRAP1
terguride for treatment of pulmonary arterial HTR2A
hypertension
terguride for treatment of pulmonary arterial HTR2B
hypertension
teriflunomide for treatment of multiple sclerosis DHODH
terlipressin for treatment of hepatorenal AVPR1A
syndrome
terlipressin for treatment of hepatorenal AVPR1B
syndrome
terlipressin for treatment of hepatorenal AVPR2
syndrome
tesetaxel antineoplastic agent BCL2
tesetaxel antineoplastic agent TUBB1
tesmilifene adjuvant to chemotherapy ABCB1
tesmilifene adjuvant to chemotherapy CYP3A4
tesmilifene adjuvant to chemotherapy CYP3A5
tesmilifene adjuvant to chemotherapy CYP3A7
tesofensine antiobesity agent SLC6A2
tesofensine antiobesity agent SLC6A4
testosterone hormone replacement, for treatment AR
of female sexual dysfunction
testosterone for treatment of female sexual AR
dysfunction
testosterone hormone replacement AR
testosterone for treatment of female sexual AR
dysfunction
testosterone hormone replacement AR
testosterone hormone replacement AR
testosterone for treatment of female sexual AR
dysfunction
tetrabenazine for treatment of Huntington's disease SLC18A2
tetrodotoxin analgesic SCN10A
tetrodotoxin analgesic SCN11A
tetrodotoxin analgesic SCN1A
tetrodotoxin analgesic SCN2A
tetrodotoxin analgesic SCN3A
tetrodotoxin analgesic SCN4A
tetrodotoxin analgesic SCN5A
tetrodotoxin analgesic SCN8A
tetrodotoxin analgesic SCN9A
tezampanel antimigraine agent, analgesic GRIA1
tezampanel antimigraine agent, analgesic GRIA2
tezampanel antimigraine agent, analgesic GRIA3
tezampanel antimigraine agent, analgesic GRIA4
tezampanel antimigraine agent, analgesic GRIK1
tezampanel antimigraine agent, analgesic GRIK2
tezampanel antimigraine agent, analgesic GRIK3
tezampanel antimigraine agent, analgesic GRIK4
tezampanel antimigraine agent, analgesic GRIK5
TG-0054 adjuvant to stem cell transplantation CXCR4
TG02, SB1317 antineoplastic agent CDK2
TG02, SB1317 antineoplastic agent ERK5
TG02, SB1317 antineoplastic agent FLT3
TG02, SB1317 antineoplastic agent JAK2
TG101348 antineoplastic agent JAK2
thalidomide antineoplastic agent FGFR2
thalidomide antineoplastic agent NFKB1
thalidomide antineoplastic agent PTGS2
thalidomide antineoplastic agent TNF
sitaxsentan for treatment of pulmonary arterial EDNRA
hypertension
ketoprofen NSAID PTGS1
ketoprofen NSAID PTGS1
ketoprofen NSAID PTGS2
ketoprofen NSAID PTGS2
pilocarpine for treatment of incontinence CHRM1
pilocarpine for treatment of incontinence CHRM2
pilocarpine for treatment of incontinence CHRM3
tolterodine for treatment of incontinence CHRM1
tolterodine for treatment of incontinence CHRM2
tolterodine for treatment of incontinence CHRM3
tolterodine for treatment of incontinence CHRM4
tolterodine for treatment of incontinence CHRM5
Ticagrelor antithrombotic P2RY12
tideglusib for treatment of Alzheimer's disease GSK3A
tideglusib for treatment of Alzheimer's disease GSK3B
tilarginine for treatment of cardiogenic shock NOS2
tiotropium for treatment of cystic fibrosis, for CHRM1
treatment of chronic obstructive
pulmonary disorder (COPD)
tiotropium for treatment of cystic fibrosis, for CHRM2
treatment of chronic obstructive
pulmonary disorder (COPD)
tiotropium for treatment of cystic fibrosis, for CHRM3
treatment of chronic obstructive
pulmonary disorder (COPD)
tipifarnib antineoplastic agent FNTA
tipifarnib antineoplastic agent FNTB
tizanidine muscle relaxant ADRA2A
tizanidine muscle relaxant ADRA2B
tizanidine muscle relaxant ADRA2C
canfosfamide antineoplastic agent GSTP1
TLN-4601 antineoplastic agent TSPO
obinepitide antiobesity agent NPY2R
obinepitide antiobesity agent PPYR1
TM30339 antiobesity agent PPYR1
TM38837 antiobesity agent CNR1
ondansetron for treatment of obsessive HTR3A
compulsive disorder (OCD)
galeterone antineoplastic agent AR
galeterone antineoplastic agent CYP17A1
tolterodine for treatment of incontinence CHRM1
tolterodine for treatment of incontinence CHRM2
tolterodine for treatment of incontinence CHRM3
tolterodine for treatment of incontinence CHRM4
tolterodine for treatment of incontinence CHRM5
tolvaptan antihypertensive agent AVPR2
Tonabersat antimigraine agent HTR1D
alprostadil for treatment of erectile PTGER1
dysfunction, for treatment of sexual
dysfunction in women
alprostadil for treatment of erectile PTGER2
dysfunction, for treatment of sexual
dysfunction in women
menadione for reducing EGFR-inhibitor- GGCX
induced dermatological side effects
menadione for reducing EGFR-inhibitor- VKORC1
induced dermatological side effects
menadione for reducing EGFR-inhibitor- VKORC1L1
induced dermatological side effects
testosterone hormone replacement AR
topiramate anticonvulsant CA2
topiramate anticonvulsant CA4
topiramate anticonvulsant GABRA1
topiramate anticonvulsant GRIK1
topiramate anticonvulsant SCN1A
topiramate anticonvulsant, antimigraine agent CA2
topiramate anticonvulsant, antimigraine agent CA4
topiramate anticonvulsant, antimigraine agent GABRA1
topiramate anticonvulsant, antimigraine agent GRIK1
topiramate anticonvulsant, antimigraine agent SCN1A
topotecan antineoplastic agent TOP1
Torcetrapib antidyslipidaemic agent CETP
morphine analgesic OPRD1
morphine analgesic OPRK1
morphine analgesic OPRM1
bosentan for treatment of pulmonary arterial EDNRA
hypertension
bosentan for treatment of pulmonary arterial EDNRB
hypertension
tramadol analgesic HTR2C
tramadol analgesic OPRK1
tramadol analgesic OPRM1
tramadol analgesic OPRM1
tramadol analgesic SLC6A2
tramadol analgesic SLC6A2
tramadol analgesic SLC6A4
tramadol analgesic SLC6A4
tramadol analgesic HTR2C
tramadol analgesic OPRK1
tramadol analgesic OPRM1
tramadol analgesic OPRM1
tramadol analgesic SLC6A2
tramadol analgesic SLC6A2
tramadol analgesic SLC6A4
tramadol analgesic SLC6A4
tramadol analgesic HTR2C
tramadol analgesic OPRK1
tramadol analgesic OPRM1
tramadol analgesic OPRM1
tramadol analgesic SLC6A2
tramadol analgesic SLC6A2
tramadol analgesic SLC6A4
tramadol analgesic SLC6A4
hom*otaurine for treatment of Alzheimer's disease APP
trandolapril antihypertensive agent ACE
tranexamic acid antimenorrhagic agent PLAT
capsaicin analgesic TRPV1
diclofenac NSAID PTGS1
diclofenac NSAID PTGS2
estradiol hormone replacement ESR1
estradiol hormone replacement ESR2
granisetron antiemetic HTR3A
lidocaine anestethic SCN10A
lidocaine anestethic SCN5A
lidocaine anestethic SCN9A
epinephrine anestethic ADRA1A
epinephrine anestethic ADRA1B
epinephrine anestethic ADRA1D
epinephrine anestethic ADRA2A
epinephrine anestethic ADRA2B
epinephrine anestethic ADRB1
epinephrine anestethic ADRB2
lidocaine anestethic SCN10A
lidocaine anestethic SCN5A
lidocaine anestethic SCN9A
oxybutynin for treatment of incontinence CHRM1
oxybutynin for treatment of incontinence CHRM2
oxybutynin for treatment of incontinence CHRM3
oxycodone analgesic OPRD1
oxycodone analgesic OPRK1
oxycodone analgesic OPRM1
fentanyl analgesic OPRD1
fentanyl analgesic OPRM1
timolol for treatment of glaucoma ADRB1
timolol for treatment of glaucoma ADRB2
travoprost for treatment of glaucoma PTGFR
trazodone antidepressant HTR1A
trazodone antidepressant HTR2A
trazodone antidepressant HTR2C
trazodone antidepressant SLC6A4
trelanserin for treatment of intermittent HTR1B
claudication
trelanserin for treatment of intermittent HTR2A
claudication
tretinoin for treatment of acne RARG
tretinoin for treatment of acne RXRB
tretinoin for treatment of acne RXRG
triamcinolone for treatment of diabetic macular NR3C1
edema
Triapine antineoplastic agent RRM2
amlodipine antihypertensive agent CACNA1C
amlodipine antihypertensive agent CACNA1D
amlodipine antihypertensive agent CACNA1S
amlodipine antihypertensive agent CACNA2D1
amlodipine antihypertensive agent CACNB2
hydrochlorothiazide antihypertensive agent SLC12A3
olmesartan antihypertensive agent AGTR1
triciribine antineoplastic agent AKT1
triciribine antineoplastic agent AKT2
triciribine antineoplastic agent AKT3
HE3286 antiinflammatory agent, DMARD NR3C1
trodusquemine antiobesity agent PTPN1
trospium for treatment of incontinence CHRM1
TTP889 anticoagulant F9
lapatinib antineoplastic agent EGFR
lapatinib antineoplastic agent ERBB2
TZP-101 for treatment of gastroparesis GHSR
TZP-102 for treatment of gastroparesis GHSR
heparin for treatment of pelvic pain of F10
bladder origin and interstitital cystitis
heparin for treatment of pelvic pain of SERPINC1
bladder origin and interstitital cystitis
lidocaine for treatment of pelvic pain of SCN10A
bladder origin and interstitital cystitis
lidocaine for treatment of pelvic pain of SCN5A
bladder origin and interstitital cystitis
lidocaine for treatment of pelvic pain of SCN9A
bladder origin and interstitital cystitis
udenafil for treatment of erectile dysfunction PDE5A
tegafur antineoplastic agent TYMS
Ulipristal contraceptive PGR
heparin antithrombotic F10
heparin antithrombotic SERPINC1
ursodeoxycholic acid for prevention of recurrence of AKR1C2
colorectal polyps
topiramate anticonvulsant CA2
topiramate anticonvulsant CA4
topiramate anticonvulsant GABRA1
topiramate anticonvulsant GRIK1
topiramate anticonvulsant SCN1A
buprenorphine antidepressant, analgesic, for OPRD1
treatment of opioid addiction
buprenorphine antidepressant, analgesic, for OPRK1
treatment of opioid addiction
buprenorphine antidepressant, analgesic, for OPRM1
treatment of opioid addiction
carbidopa antiparkinson agent DDC
melevodopa antiparkinson agent DRD1
melevodopa antiparkinson agent DRD2
melevodopa antiparkinson agent DRD3
melevodopa antiparkinson agent DRD4
melevodopa antiparkinson agent DRD5
V158866 analgesic FAAH
V24343 antiobesity agent CNR1
V3381 analgesic, neuropathic pain GRIN1
V3381 analgesic, neuropathic pain GRIN2A
V3381 analgesic, neuropathic pain GRIN2B
V3381 analgesic, neuropathic pain GRIN2C
V3381 analgesic, neuropathic pain GRIN2D
V3381 analgesic, neuropathic pain GRIN3A
V3381 analgesic, neuropathic pain GRIN3B
V3381 analgesic, neuropathic pain MAOA
V3381 analgesic, neuropathic pain MAOB
VA106483 for treatment of BPH-related urinary AVPR2
symptoms
VA111913 for treatment of dysmenorrhea AVPR1A
VA111913 for treatment of dysmenorrhea AVPR1B
VA111913 for treatment of dysmenorrhea AVPR2
Vadimezan antineoplastic agent HIPK2
Vadimezan antineoplastic agent KDR
Vadimezan antineoplastic agent PIM3
valproic acid anticonvulsant ABAT
valproic acid anticonvulsant ACADSB
valproic acid anticonvulsant HDAC9
valproic acid for treatment of basal cell carcinoma ABAT
valproic acid for treatment of basal cell carcinoma ACADSB
valproic acid for treatment of basal cell carcinoma HDAC9
valsartan antihypertensive agent AGTR1
vapitadine antiallergy agent HRH1
vapreotide for treatment of liver cirrhosis- SSTR2
related variceal bleeding
vapreotide for treatment of liver cirrhosis- SSTR5
related variceal bleeding
vardenafil for treatment of erectile dysfunction PDE5A
varenicline smoking-cessation agent CHRNA3
varenicline smoking-cessation agent CHRNA4
varenicline smoking-cessation agent CHRNA7
varenicline smoking-cessation agent CHRNB2
varenicline smoking-cessation agent CHRNB4
varespladib antiinflammatory agent PLA2G10
varespladib antiinflammatory agent PLA2G2A
varespladib antiinflammatory agent PLA2G5
varespladib antiinflammatory agent PLA2G10
varespladib antiinflammatory agent PLA2G2A
varespladib antiinflammatory agent PLA2G5
ethinyl estradiol contraceptive ESR1
norethindrone contraceptive PGR
Vatalanib antineoplastic agent FLT1
Vatalanib antineoplastic agent FLT4
Vatalanib antineoplastic agent KDR
Vatalanib antineoplastic agent KIT
Vatalanib antineoplastic agent PDGFRA
Vatalanib antineoplastic agent PDGFRB
Vatalanib antineoplastic agent FLT1
Vatalanib antineoplastic agent FLT4
Vatalanib antineoplastic agent KDR
Vatalanib antineoplastic agent KIT
Vatalanib antineoplastic agent PDGFRA
Vatalanib antineoplastic agent PDGFRB
VEL-0230 antirheumatic agent CTSK
bortezomib antineoplastic agent PSMB1
bortezomib antineoplastic agent PSMB2
bortezomib antineoplastic agent PSMB5
bortezomib antineoplastic agent PSMD1
bortezomib antineoplastic agent PSMD2
bupropion antidepressant, appetite SLC6A2
suppressant, smoking-cessation agent
bupropion antidepressant, appetite SLC6A3
suppressant, smoking-cessation agent
velneperit antiobesity agent NPY5R
velusetrag motilitant HTR4
fluticasone furoate antiinflammatory NR3C1
agent, glucocorticoid
verapamil antihypertensive agent CACNA1C
verapamil antihypertensive agent CACNA1D
verapamil antihypertensive agent CACNA1F
verapamil antihypertensive agent CACNA1S
verapamil antihypertensive agent CACNB1
verapamil antihypertensive agent CACNB2
verapamil antihypertensive agent CACNB3
verapamil antihypertensive agent CACNB4
vestipitant for treatment of tinnitus, hypnotic TACR1
VGX-1027 antiinflammatory agent, DMARD unknown
VIA-2291 antiatherosclerotic agent ALOX5
VIA-3196 antidyslipidaemic agent THRB
Calcitonin antiosteoporotic agent CALCR
methotrexate DMARD DHFR
vicriviroc antiviral agent, HIV CCR5
vidofludimus antiinflammatory agent, DMARD DHODH
vidofludimus antiinflammatory agent, DMARD IL17A
vidofludimus antiinflammatory agent, DMARD IL17B
vidofludimus antiinflammatory agent, DMARD IL17C
vidofludimus antiinflammatory agent, DMARD IL17D
vidofludimus antiinflammatory agent, DMARD IL17E
Vigabatrin for treatment of addiction ABAT
Vigabatrin for treatment of addiction GABBR1
vilazodone antidepressant HTR1A
vildagliptin antidiabetic DPP4
vincristine antineoplastic agent TUBA4A
vincristine antineoplastic agent TUBB
vinorelbine antineoplastic agent TUBB
BIIB014 antiparkinson agent ADORA2A
Virulizin antineoplastic agent IL12A
Virulizin antineoplastic agent IL12B
naltrexone for treatment of substance abuse OPRD1
naltrexone for treatment of substance abuse OPRK1
naltrexone for treatment of substance abuse OPRM1
Voclosporin antiinflammatory PPIA
agent, DMARD, immunosuppressant
Voclosporin antiinflammatory PPP3CA
agent, DMARD, immunosuppressant
Voclosporin antiinflammatory PPP3CB
agent, DMARD, immunosuppressant
Voclosporin antiinflammatory PPP3CC
agent, DMARD, immunosuppressant
vofopitant for treatment of post-traumatic stress TACR1
disorder, hypnotic
voglibose antidiabetic MGAM
volinanserin hypnotic HTR2A
vorapaxar cardiovascular agent F2R
vorapaxar cardiovascular agent F2RL2
vorapaxar cardiovascular agent F2RL3
Voreloxin antineoplastic agent TOP2A
Voreloxin antineoplastic agent TOP2B
Histrelin antineoplastic agent GNRHR
Histrelin antineoplastic agent GNRHR2
TRPV1 antagonist analgesic TRPV1
VR-147 antimigraine agent HTR1B
VR-147 antimigraine agent HTR1D
heparin for treatment of cystic fibrosis F10
heparin for treatment of cystic fibrosis SERPINC1
etodolac for treatment of cancer cachexia PTGS1
etodolac NSAID PTGS2
propranolol for treatment of cancer cachexia ADRB1
VTP-27999 antihypertensive agent REN
VTX-1463 antiallergy agent TLR8
VTX-2337 antineoplastic agent TLR8
VX-509 antiinflammatory agent, DMARD JAK3
WX-554 antineoplastic agent MAP2K1
WX-554 antineoplastic agent MAP2K2
WX-554 antineoplastic agent MAP2K3
WX-554 antineoplastic agent MAP2K4
WX-554 antineoplastic agent MAP2K5
WX-554 antineoplastic agent MAP2K6
WX-554 antineoplastic agent MAP2K7
tozasertib antineoplastic agent AURKA
tozasertib antineoplastic agent AURKB
tozasertib antineoplastic agent AURKC
VX-702 antiinflammatory MAPK11
agent, cardiovascular agent
VX-702 antiinflammatory MAPK12
agent, cardiovascular agent
VX-702 antiinflammatory MAPK13
agent, cardiovascular agent
VX-702 antiinflammatory MAPK14
agent, cardiovascular agent
VX-765 antipsoriatic agent, anticonvulsant CASP1
ivacaftor for treatment of cystic fibrosis CFTR
VX-809 for treatment of cystic fibrosis CFTR
ivacaftor for treatment of cystic fibrosis CFTR
VX-809 for treatment of cystic fibrosis CFTR
WX-UK1 antineoplastic agent PLAU
emzetibe antidyslipidaemic agent NPC1L1
emzetibe antidyslipidaemic agent SOAT1
simvastatin antidyslipidaemic agent HMGCR
NRP104 for treatment of ADHD ADRA1B
NRP104 for treatment of ADHD SLC18A2
NRP104 for treatment of ADHD SLC6A3
xaliproden neuroprotectant HTR1A
XL019 antineoplastic agent JAK2
cabozantinib antineoplastic agent KDR
cabozantinib antineoplastic agent MET
XL228 antineoplastic agent ABL1
XL228 antineoplastic agent AURKA
XL228 antineoplastic agent IGF1R
XL228 antineoplastic agent SRC
XL281 antineoplastic agent ARAF
XL281 antineoplastic agent BRAF
XL281 antineoplastic agent RAF1
XL418 antineoplastic agent AKT1
XL418 antineoplastic agent AKT2
XL418 antineoplastic agent AKT3
XL418 antineoplastic agent RPS6KB1
XL647 antineoplastic agent EGFR
XL647 antineoplastic agent EPHB4
XL647 antineoplastic agent ERBB2
XL647 antineoplastic agent FLT1
XL647 antineoplastic agent FLT4
XL647 antineoplastic agent KDR
XL765 antineoplastic agent MTOR
XL765 antineoplastic agent PIK3CA
XL765 antineoplastic agent PIK3CD
XL765 antineoplastic agent PIK3CG
XL820 antineoplastic agent FLT1
XL820 antineoplastic agent FLT4
XL820 antineoplastic agent KDR
XL820 antineoplastic agent KIT
XL820 antineoplastic agent PDGFRA
XL820 antineoplastic agent PDGFRB
XL844 antineoplastic agent CHEK1
XL844 antineoplastic agent CHEK2
XL880 antineoplastic agent KDR
XL880 antineoplastic agent MET
XL888 antineoplastic agent HSP90AA1
XL888 antineoplastic agent HSP90AB1
XL999 antineoplastic agent AXL
XL999 antineoplastic agent FGFR1
XL999 antineoplastic agent FLT1
XL999 antineoplastic agent FLT3
XL999 antineoplastic agent FLT4
XL999 antineoplastic agent KDR
XL999 antineoplastic agent KIT
XL999 antineoplastic agent PDGFRB
camptothecin antineoplastic agent TOP1
XMT-1107 antineoplastic agent METAP2
tranexamic acid for treatment of menorrhagia PLG
XP13512 for treatment of restless legs CACNA1B
syndrome
XP13512 for treatment of restless legs CACNA2D1
syndrome
XP13512 for treatment of restless legs CACNA2D2
syndrome
R-baclofen for treatment of gastrointestinal GABBR1
reflux disease
R-baclofen for treatment of gastrointestinal GABBR2
reflux disease
XP21279 antiparkinson agent DRD1
XP21279 antiparkinson agent DRD2
XP21279 antiparkinson agent DRD3
XP21279 antiparkinson agent DRD4
XP21279 antiparkinson agent DRD5
gantofiban antithrombotic, antiatherosclerotic ITGA2B
agent
gantofiban antithrombotic, antiatherosclerotic ITGB3
agent
finasteride antineoplastic agent AKR1D1
finasteride antineoplastic agent SRD5A1
finasteride antineoplastic agent SRD5A2
YM-178 for treatment of overactive bladder ADRB3
YM-598 antineoplastic agent EDNRA
vandetanib antineoplastic agent EGFR
vandetanib antineoplastic agent FLT1
vandetanib antineoplastic agent FLT4
vandetanib antineoplastic agent KDR
vandetanib antineoplastic agent RET
zafirlukast antiasthmatic agent CYSLTR1
zaleplon hypnotic GABRA1
zaleplon hypnotic TSPO
ranitidine antiulcer agent HRH2
beloranib antiobesity agent METAP2
zibotentan antineoplastic agent EDNRA
ziconotide analgesic CACNA1B
ziprasidone antipsychotic agent DRD2
ziprasidone antipsychotic agent HTR2A
ondansetron antiemetic HTR3A
zoledronate antiosteoporotic agent FDPS
zoledronate antiosteoporotic agent GGPS1
zolmitriptan antimigraine agent HTR1A
zolmitriptan antimigraine agent HTR1B
zolmitriptan antimigraine agent HTR1D
zolmitriptan antimigraine agent HTR1F
sertraline antidepressant, for treatment of SLC6A3
obsessive compulsive disorder
(OCD)
sertraline antidepressant, for treatment of SLC6A4
obsessive compulsive disorder
(OCD)
zolpidem hypnotic GABRA1
zonisamide anticonvulsant CACNA1G
zonisamide anticonvulsant CACNA1H
zonisamide anticonvulsant CACNA1I
zonisamide anticonvulsant SCN11A
zonisamide anticonvulsant SCN1A
zonisamide anticonvulsant SCN1B
zonisamide anticonvulsant SCN2A
zonisamide anticonvulsant SCN2B
zonisamide anticonvulsant SCN3A
zonisamide anticonvulsant SCN3B
zonisamide anticonvulsant SCN4A
zonisamide anticonvulsant SCN4B
zonisamide anticonvulsant SCN5A
zonisamide anticonvulsant SCN9A
zosuquidar adjuvant to chemotherapy ABCB1
zucapsaicin analgesic TRPV1
hydrocodone analgesic OPRD1
hydrocodone analgesic OPRM1
zileuton antiinflammatory agent ALOX5
ASP015K for treatment of rheumatoid arthritis JAK1
ASP015K for treatment of rheumatoid arthritis JAK3
CHF 6001 antiasthmatic; for treatment of PDE4A
chronic obstructive pulmonary
disease
CHF 6001 antiasthmatic; for treatment of PDE4B
chronic obstructive pulmonary
disease
CUDC-427 antineoplastic agent XIAP
ARQ 087 antineoplastic agent FGFR1
ARQ 087 antineoplastic agent FGFR2
ARQ 087 antineoplastic agent FGFR3
deuterated dextromethorphan for treatment of neurologic and GRIN3A
psychiatric disorders
deuterated dextromethorphan for treatment of neurologic and OPRS1
psychiatric disorders
olanzapine antipsychotic agent ADRA1A
olanzapine antipsychotic agent ADRA1B
olanzapine antipsychotic agent ADRA2A
olanzapine antipsychotic agent ADRA2B
olanzapine antipsychotic agent ADRA2C
olanzapine antipsychotic agent CHRM1
olanzapine antipsychotic agent CHRM2
olanzapine antipsychotic agent CHRM3
olanzapine antipsychotic agent CHRM4
olanzapine antipsychotic agent CHRM5
olanzapine antipsychotic agent DRD1
olanzapine antipsychotic agent DRD2
olanzapine antipsychotic agent DRD3
olanzapine antipsychotic agent DRD4
olanzapine antipsychotic agent DRD5
olanzapine antipsychotic agent HRH1
olanzapine antipsychotic agent HTR1A
olanzapine antipsychotic agent HTR1B
olanzapine antipsychotic agent HTR1D
olanzapine antipsychotic agent HTR1E
olanzapine antipsychotic agent HTR2A
olanzapine antipsychotic agent HTR2C
olanzapine antipsychotic agent HTR3A
olanzapine antipsychotic agent HTR6
olanzapine antipsychotic agent HTR7
samidoprhan for treatment of addiction MOR
Ethyl eicosapentaenoic acid for treatment of cardiovascular PPARD
disorders
Ethyl eicosapentaenoic acid for treatment of cardiovascular PPARG
disorders
Ethyl eicosapentaenoic acid for treatment of cardiovascular PTGS1
disorders
Ethyl eicosapentaenoic acid for treatment of cardiovascular PTGS2
disorders
BCX4161 for treatment of hereditary KLKB1
angioedema
ACEBUTOLOL Antihypertensive Agents ADRB1
ACENOCOUMAROL Anticoagulants VKORC1
ACEPROMETAZINE Hypnotics and Sedatives HRH1
ACETAZOLAMIDE Anticonvulsants; Diuretics; CA1
antiglaucomic agent
ACETAZOLAMIDE Anticonvulsants; Diuretics; CA12
antiglaucomic agent
ACETAZOLAMIDE Anticonvulsants; Diuretics; CA2
antiglaucomic agent
ACETOHEXAMIDE Hypoglycemic Agents KCNJ1
ACETOPHENAZINE Antipsychotic Agents DRD1
ACETOPHENAZINE Antipsychotic Agents DRD2
ACETYLDIGITOXIN Anti-Arrhythmia Agents ATP1A1
ACITRETIN Keratolytic Agents RARA
ADAPALENE Dermatologic Agents RARA
ADAPALENE Dermatologic Agents RARB
ADAPALENE Dermatologic Agents RARG
ADAPALENE Dermatologic Agents RXRA
ADAPALENE Dermatologic Agents RXRB
ADAPALENE Dermatologic Agents RXRG
ADINAZOLAM Anti-anxiety Agents; anticonvulsant GABRA1
ADINAZOLAM Anti-anxiety Agents; anticonvulsant GABRA2
ADINAZOLAM Anti-anxiety Agents; anticonvulsant GABRA3
ADINAZOLAM Anti-anxiety Agents; anticonvulsant GABRA5
ADINAZOLAM Anti-anxiety Agents; anticonvulsant GABRB1
ADINAZOLAM Anti-anxiety Agents; anticonvulsant GABRB2
ADINAZOLAM Anti-anxiety Agents; anticonvulsant GABRB3
ADINAZOLAM Anti-anxiety Agents; anticonvulsant GABRD
ADINAZOLAM Anti-anxiety Agents; anticonvulsant GABRE
ADINAZOLAM Anti-anxiety Agents; anticonvulsant GABRG1
ADINAZOLAM Anti-anxiety Agents; anticonvulsant GABRG2
ADINAZOLAM Anti-anxiety Agents; anticonvulsant GABRG3
ADINAZOLAM Anti-anxiety Agents; anticonvulsant GABRP
ADINAZOLAM Anti-anxiety Agents; anticonvulsant GABRR1
ADINAZOLAM Anti-anxiety Agents; anticonvulsant GABRR2
ADINAZOLAM Anti-anxiety Agents; anticonvulsant GABRR3
ALCAFTADINE Anti-Allergic Agents HRH1
ALCLOMETASONE Anti-Inflammatory Agents; Anti- NR3C1
pruritics; Corticosteroids, topical
ALENDRONATE Bisphosphonates FDPS
ALFENTANIL Analgesics, Opioid OPRM1
Alitretionine Antineoplastic Agents RARA
Alitretionine Antineoplastic Agents RARB
Alitretionine Antineoplastic Agents RARG
Alitretionine Antineoplastic Agents RXRA
Alitretionine Antineoplastic Agents RXRB
Alitretionine Antineoplastic Agents RXRG
ALMITRINE Respiratory Stimulant Agents ATP1A1
ALPRENOLOL Anti-Arrhythmia Agents; ADRB1
Antihypertensive Agents
ALPRENOLOL Anti-Arrhythmia Agents; ADRB2
Antihypertensive Agents
ALSEROXYLON Antipsychotic Agents; SLC18A2
Antihypertensive Agents
ALVIMOPAN Opiate Antagonists OPRM1
AMBENONIUM Antimyasthenics ACHE
AMCINONIDE Anti-Inflammatory Agents; Anti- NR3C1
pruritics; Corticosteroids, topical
AMINOCAPROIC ACID Antifibrinolytic Agents PLG
AMINOGLUTETHIMIDE Antineoplastic agents CYP19A1
AMRINONE Cardiotonic Agents; PDE3A
Phosphodiesterase Inhibitors
AMRINONE Cardiotonic Agents; PDE4B
Phosphodiesterase Inhibitors
ANILERIDINE Analgesics; Narcotics OPRM1
ANISINDIONE Anticoagulants GGCX
ANISOTROPINE Antispasmodics; Anti-ulcer Agents CHRM1
METHYLBROMIDE
ANISOTROPINE Antispasmodics; Anti-ulcer Agents CHRM2
METHYLBROMIDE
ANISOTROPINE Antispasmodics; Anti-ulcer Agents CHRM3
METHYLBROMIDE
APRACLONIDINE Antiglaucomic Agents ADRA2A
APRINDINE Anti-Arrhythmia Agents SCN5A
ARBUTAMINE Cardiotonic Agents ADRB1
ARDEPARIN Anticoagulants SERPINC1
ARDEPARIN Anticoagulants SERPIND1
ARFORMOTEROL Bronchodilator Agents ADRB2
ASTEMIZOLE Anti-Allergic Agents HRH1
ATENOLOL Anti-Arrhythmia Agents; ADRB1
Antihypertensive Agents
ATRACURIUM Muscle Relaxants CHRNA2
AURANOFIN Antirheumatic Agents IKBKB
AZATADINE Anti-Allergic Agents HRH1
BENDROFLUMETHIAZIDE Antihypertensive Agents; Diuretics SLC12A3
BENTIROMIDE Diagnostic Agents HPN
BENTIROMIDE Diagnostic Agents HPN
BENZOCAINE Anesthetics, Local SCN10A
BENZONATATE Antitussive Agents SCN5A
BENZPHETAMINE Central Nervous System Stimulants ADRA1A
BENZPHETAMINE Central Nervous System Stimulants ADRA2A
BENZQUINAMIDE Antiemetics; Antipsychotic Agents CHRM1
BENZQUINAMIDE Antiemetics; Antipsychotic Agents CHRM2
BENZQUINAMIDE Antiemetics; Antipsychotic Agents CHRM3
BENZQUINAMIDE Antiemetics; Antipsychotic Agents CHRM4
BENZQUINAMIDE Antiemetics; Antipsychotic Agents CHRM5
BENZQUINAMIDE Antiemetics; Antipsychotic Agents HRH1
BENZTHIAZIDE Antihypertensive Agents; Diuretics SLC12A3
BENZTROPINE Antiparkinson Agents CHRM1
BENZTROPINE Antiparkinson Agents SLC6A3
BENZYLPENICILLOYL Diagnostic Agents FCER1A
POLYLYSINE
BENZYLPENICILLOYL Diagnostic Agents FCER1G
POLYLYSINE
BEPRIDIL Anti-Arrhythmia Agents; ATP1A1
Antihypertensive Agents
BEPRIDIL Anti-Arrhythmia Agents; CACNA1A
Antihypertensive Agents
BEPRIDIL Anti-Arrhythmia Agents; KCNQ1
Antihypertensive Agents
BEPRIDIL Anti-Arrhythmia Agents; SCN5A
Antihypertensive Agents
BEPRIDIL Anti-Arrhythmia Agents; TNNC1
Antihypertensive Agents
BETAXOLOL Antihypertensive Agents ADRB1
BETAZOLE Diagnostic Agents HRH2
BETHANECHOL Parasympathomimetics CHRM1
BETHANIDINE Antihypertensive Agents ADRA1A
BETHANIDINE Antihypertensive Agents ADRA1B
BETHANIDINE Antihypertensive Agents ADRA1D
BETHANIDINE Antihypertensive Agents ADRA2A
BETHANIDINE Antihypertensive Agents ADRA2B
BETHANIDINE Antihypertensive Agents ADRA2C
BETHANIDINE Antihypertensive Agents SLC6A2
BEVANTOLOL Antihypertensive Agents ADRB1
BIPERIDEN Antidyskinetics CHRM1
BIPERIDEN Antidyskinetics CHRNA2
BISOPROLOL Antihypertensive Agents ADRB1
BRINZOLAMIDE Antiglaucomic Agents CA2
BROMAZEPAM Hypnotics and Sedatives GABRA1
BROMAZEPAM Hypnotics and Sedatives GABRA2
BROMAZEPAM Hypnotics and Sedatives GABRA3
BROMAZEPAM Hypnotics and Sedatives GABRA4
BROMAZEPAM Hypnotics and Sedatives GABRA5
BROMAZEPAM Hypnotics and Sedatives GABRA6
BROMAZEPAM Hypnotics and Sedatives GABRB1
BROMAZEPAM Hypnotics and Sedatives GABRB2
BROMAZEPAM Hypnotics and Sedatives GABRB3
BROMAZEPAM Hypnotics and Sedatives GABRD
BROMAZEPAM Hypnotics and Sedatives GABRE
BROMAZEPAM Hypnotics and Sedatives GABRG1
BROMAZEPAM Hypnotics and Sedatives GABRG2
BROMAZEPAM Hypnotics and Sedatives GABRG3
BROMAZEPAM Hypnotics and Sedatives GABRP
BROMAZEPAM Hypnotics and Sedatives GABRQ
BROMAZEPAM Hypnotics and Sedatives GABRR1
BROMAZEPAM Hypnotics and Sedatives GABRR2
BROMAZEPAM Hypnotics and Sedatives GABRR3
BROMODIPHENHYDRAMINE Anti-Allergic Agents HRH1
BROMPHENIRAMINE Anti-Allergic Agents HRH1
BUCLIZINE Antiemetics CHRM1
BUCLIZINE Antiemetics HRH1
BUMETANIDE Antihypertensive Agents; Diuretics SLC12A1
BUMETANIDE Antihypertensive Agents; Diuretics SLC12A2
BUMETANIDE Antihypertensive Agents; Diuretics SLC12A4
BUMETANIDE Antihypertensive Agents; Diuretics SLC12A5
BUSPIRONE Anti-anxiety Agents DRD2
BUSPIRONE Anti-anxiety Agents HTR1A
BUTABARBITAL Hypnotics and Sedatives CHRNA4
BUTABARBITAL Hypnotics and Sedatives CHRNA7
BUTABARBITAL Hypnotics and Sedatives GABRA1
BUTABARBITAL Hypnotics and Sedatives GABRA2
BUTABARBITAL Hypnotics and Sedatives GABRA3
BUTABARBITAL Hypnotics and Sedatives GABRA4
BUTABARBITAL Hypnotics and Sedatives GABRA5
BUTABARBITAL Hypnotics and Sedatives GABRA6
BUTABARBITAL Hypnotics and Sedatives GRIA2
BUTABARBITAL Hypnotics and Sedatives GRIK2
BUTALBITAL Analgesics CHRNA4
BUTALBITAL Analgesics CHRNA7
BUTALBITAL Analgesics GABRA1
BUTALBITAL Analgesics GABRA2
BUTALBITAL Analgesics GABRA3
BUTALBITAL Analgesics GABRA4
BUTALBITAL Analgesics GABRA5
BUTALBITAL Analgesics GABRA6
BUTALBITAL Analgesics GRIA2
BUTALBITAL Analgesics GRIK2
BUTETHAL Hypnotics and Sedatives CHRNA4
BUTETHAL Hypnotics and Sedatives CHRNA7
BUTETHAL Hypnotics and Sedatives GABRA1
BUTETHAL Hypnotics and Sedatives GABRA2
BUTETHAL Hypnotics and Sedatives GABRA3
BUTETHAL Hypnotics and Sedatives GABRA4
BUTETHAL Hypnotics and Sedatives GABRA5
BUTETHAL Hypnotics and Sedatives GABRA6
BUTETHAL Hypnotics and Sedatives GRIA2
BUTETHAL Hypnotics and Sedatives GRIK2
BUTORPHANOL Analgesics, Opioid OPRD1
BUTORPHANOL Analgesics, Opioid OPRK1
BUTORPHANOL Analgesics, Opioid OPRM1
CABERGOLINE Antiparkinson Agents DRD2
CAFFEINE Central Nervous System Stimulants ADORA1
CAFFEINE Central Nervous System Stimulants ADORA2A
CAFFEINE Central Nervous System Stimulants PDE4B
CALCIPOTRIOL Dermatologic Agents VDR
CANDOXATRIL Antihypertensive Agents ACE
CANDOXATRIL Antihypertensive Agents MME
CAPTOPRIL Antihypertensive Agents ACE
CARBACHOL Antiglaucomic Agents CHRM1
CARBACHOL Antiglaucomic Agents CHRM2
CARBACHOL Antiglaucomic Agents CHRNA2
CARBETOCIN Labor Inducing Agents OXTR
CARBIMAZOLE Antithyroid Agents TPO
CARBINOXAMINE Anti-Allergic Agents CHRM1
CARBINOXAMINE Anti-Allergic Agents HRH1
CARBOPROST Abortifacient Agents PTGER1
TROMETHAMINE
CARPHENAZINE Antipsychotic Agents DRD1
CARPHENAZINE Antipsychotic Agents DRD2
CARPHENAZINE Antipsychotic Agents DRD5
CARPROFEN Anti-Inflammatory Agents, Non- PTGS2
Steroidal
CARTEOLOL Antiglaucomic Agents ADRB1
CARTEOLOL Antiglaucomic Agents ADRB2
CERULETIDE Diagnostic Agents CCKAR
CEVIMELINE Parasympathomimetics CHRM1
CEVIMELINE Parasympathomimetics CHRM3
CHLOPHEDIANOL Antitussive Agents HRH1
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRA1
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRA2
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRA3
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRA4
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRA5
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRA6
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRB1
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRB2
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRB3
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRD
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRE
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRG1
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRG2
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRG3
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRP
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRQ
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRR1
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRR2
CHLORDIAZEPOXIDE Hypnotics and Sedatives GABRR3
CHLORMERODRIN Antihypertensive Agents; Diuretics SLC12A1
CHLORMEZANONE Anti-anxiety Agents; Muscle BZRP
Relaxants
CHLOROPROCAINE Anesthetics, Local SCN10A
CHLOROTHIAZIDE Antihypertensive Agents; Diuretics CA1
CHLOROTHIAZIDE Antihypertensive Agents; Diuretics CA2
CHLOROTHIAZIDE Antihypertensive Agents; Diuretics CA4
CHLOROTHIAZIDE Antihypertensive Agents; Diuretics SLC12A3
CHLOROTRIANISENE Hormone Replacement Agents ESR1
CHLORPHENIRAMINE Anti-Allergic Agents HRH1
CHLORPROPAMIDE Hypoglycemic Agents KCNJ1
CHLORPROTHIXENE Antipsychotic Agents DRD1
CHLORPROTHIXENE Antipsychotic Agents DRD2
CHLORPROTHIXENE Antipsychotic Agents DRD3
CHLORPROTHIXENE Antipsychotic Agents HRH1
CHLORPROTHIXENE Antipsychotic Agents HTR2A
CHLORPROTHIXENE Antipsychotic Agents HTR2B
CHLORPROTHIXENE Antipsychotic Agents HTR2C
CHLORTHALIDONE Antihypertensive Agents; Diuretics SLC12A1
CHLORZOXAZONE Muscle Relaxants KCNMA1
CICLESONIDE Anti-Inflammatory Agents; Anti- NR3C1
allergic agents; Glucocorticoids
CILASTATIN Adjuvants, enzyme inhibitors DPEP1
CILAZAPRIL Antihypertensive Agents ACE
CILOSTAZOL Platelet Aggregation Inhibitors PDE3A
CIMETIDINE GI Anti-Ulcer Agents, HRH2
antihistamines
CINACALCET Calcimimetics CASR
CINALUKAST Anti-Asthmatic Agents CYSLTR1
CINNARIZINE Anti-Allergic Agents HRH1
CINOLAZEPAM Hypnotics and Sedatives GABRA1
CINOLAZEPAM Hypnotics and Sedatives GABRA2
CINOLAZEPAM Hypnotics and Sedatives GABRA3
CINOLAZEPAM Hypnotics and Sedatives GABRA5
CINOLAZEPAM Hypnotics and Sedatives GABRB1
CINOLAZEPAM Hypnotics and Sedatives GABRB2
CINOLAZEPAM Hypnotics and Sedatives GABRB3
CINOLAZEPAM Hypnotics and Sedatives GABRD
CINOLAZEPAM Hypnotics and Sedatives GABRE
CINOLAZEPAM Hypnotics and Sedatives GABRG1
CINOLAZEPAM Hypnotics and Sedatives GABRG2
CINOLAZEPAM Hypnotics and Sedatives GABRG3
CINOLAZEPAM Hypnotics and Sedatives GABRP
CINOLAZEPAM Hypnotics and Sedatives GABRR1
CINOLAZEPAM Hypnotics and Sedatives GABRR2
CINOLAZEPAM Hypnotics and Sedatives GABRR3
CISAPRIDE Parasympathomimetics HTR4
CISATRACURIUM Neuromuscular Blocking Agents CHRNA2
BESYLATE
CITALOPRAM Antidepressive Agents, Second- SLC6A4
Generation
CLEMASTINE Anti-Allergic Agents HRH1
CLENBUTEROL Bronchodilator Agents ADRB2
CLIDINIUM GI Anti-Ulcer Agents, CHRM1
anticholinergic; Antispasmodics
CLOCORTOLONE Anti-Inflammatory Agents; Anti- NR3C1
pruritics; Corticosteroids, topical
CLOFIBRATE Anticholesteremic Agents PPARA
CLOMIPRAMINE Antidepressive Agents, Tricyclic SLC6A2
CLOMIPRAMINE Antidepressive Agents, Tricyclic SLC6A4
CLORAZEPATE Hypnotics and Sedatives BZRP
CLORAZEPATE Hypnotics and Sedatives GABRA1
CLORAZEPATE Hypnotics and Sedatives GABRA2
CLORAZEPATE Hypnotics and Sedatives GABRA3
CLORAZEPATE Hypnotics and Sedatives GABRA4
CLORAZEPATE Hypnotics and Sedatives GABRA5
CLORAZEPATE Hypnotics and Sedatives GABRA6
CLORAZEPATE Hypnotics and Sedatives GABRB1
CLORAZEPATE Hypnotics and Sedatives GABRB2
CLORAZEPATE Hypnotics and Sedatives GABRB3
CLORAZEPATE Hypnotics and Sedatives GABRD
CLORAZEPATE Hypnotics and Sedatives GABRE
CLORAZEPATE Hypnotics and Sedatives GABRG1
CLORAZEPATE Hypnotics and Sedatives GABRG2
CLORAZEPATE Hypnotics and Sedatives GABRG3
CLORAZEPATE Hypnotics and Sedatives GABRP
CLORAZEPATE Hypnotics and Sedatives GABRQ
CLORAZEPATE Hypnotics and Sedatives GABRR1
CLORAZEPATE Hypnotics and Sedatives GABRR2
CLORAZEPATE Hypnotics and Sedatives GABRR3
CLOTIAZEPAM Hypnotics and Sedatives GABRA1
CLOTIAZEPAM Hypnotics and Sedatives GABRA2
CLOTIAZEPAM Hypnotics and Sedatives GABRA3
CLOTIAZEPAM Hypnotics and Sedatives GABRA5
CLOTIAZEPAM Hypnotics and Sedatives GABRB1
CLOTIAZEPAM Hypnotics and Sedatives GABRB2
CLOTIAZEPAM Hypnotics and Sedatives GABRB3
CLOTIAZEPAM Hypnotics and Sedatives GABRD
CLOTIAZEPAM Hypnotics and Sedatives GABRE
CLOTIAZEPAM Hypnotics and Sedatives GABRG1
CLOTIAZEPAM Hypnotics and Sedatives GABRG2
CLOTIAZEPAM Hypnotics and Sedatives GABRG3
CLOTIAZEPAM Hypnotics and Sedatives GABRP
CLOTIAZEPAM Hypnotics and Sedatives GABRR1
CLOTIAZEPAM Hypnotics and Sedatives GABRR2
CLOTIAZEPAM Hypnotics and Sedatives GABRR3
CLOZAPINE Antipsychotic Agents DRD1
CLOZAPINE Antipsychotic Agents DRD2
CLOZAPINE Antipsychotic Agents DRD4
CLOZAPINE Antipsychotic Agents HRH1
CLOZAPINE Antipsychotic Agents HRH4
CLOZAPINE Antipsychotic Agents HTR1A
CLOZAPINE Antipsychotic Agents HTR2A
CLOZAPINE Antipsychotic Agents HTR2C
COCAINE local anesthetic DRD3
COCAINE local anesthetic OPRK1
COCAINE local anesthetic SCN10A
COCAINE local anesthetic SCN11A
COCAINE local anesthetic SCN5A
COCAINE local anesthetic SLC6A2
COCAINE local anesthetic SLC6A3
COCAINE local anesthetic SLC6A4
CODEINE Analgesics, Opioid; Antitussive OPRD1
Agents
CODEINE Analgesics, Opioid; Antitussive OPRK1
Agents
CODEINE Analgesics, Opioid; Antitussive OPRM1
Agents
CONJUGATED ESTROGENS Hormone Replacement Agents ESR1
CROMOGLICATE Anti-Asthmatic Agents KCNMA1
CYCLIZINE Antiemetics HRH1
CYCLOBENZAPRINE Antidepressive Agents, Tricyclic HTR2A
CYCLOPENTOLATE Mydriatics CHRM1
CYCLOTHIAZIDE Antihypertensive Agents; Diuretics FXYD2
CYCRIMINE Antiparkinson Agents CHRM1
CYPROHEPTADINE Anti-Allergic Agents; Appetite HRH1
Stimulant
CYPROHEPTADINE Anti-Allergic Agents; Appetite HTR2A
Stimulant
CYPROTERONE Hypersexuality-inhibiting agents; AR
Antihirsutism agents
DACARBAZINE Antineoplastic Agents POLA2
DALFAMPRIDINE MS-treatment KCNA1
DANAZOL Antiendometriosis Agent, ESR1
Antineoplastic Agent
DANAZOL Antiendometriosis Agent, GNRHR
Antineoplastic Agent
DANAZOL Antiendometriosis Agent, GNRHR2
Antineoplastic Agent
DANTROLENE Muscle Relaxants RYR1
DAPIPRAZOLE ophthalmological agent ADRA1A
DAPIPRAZOLE ophthalmological agent ADRA1B
DAPIPRAZOLE ophthalmological agent ADRA1D
DEBRISOQUIN Antihypertensive Agents ADRA1A
DEBRISOQUIN Antihypertensive Agents ADRA1B
DEBRISOQUIN Antihypertensive Agents ADRA1D
DEBRISOQUIN Antihypertensive Agents ADRA2A
DEBRISOQUIN Antihypertensive Agents ADRA2B
DEBRISOQUIN Antihypertensive Agents ADRA2C
DECAMETHONIUM Muscle Relaxants CHRNA2
DEMECARIUM BROMIDE Antiglaucomic Agents ACHE
DEMECARIUM BROMIDE Antiglaucomic Agents BCHE
DESERPIDINE Antihypertensive Agents ACE
DESFLURANE inhalation anesthetics ATP2C1
DESFLURANE inhalation anesthetics ATP5D
DESFLURANE inhalation anesthetics GABRA1
DESFLURANE inhalation anesthetics GLRA1
DESFLURANE inhalation anesthetics GRIA1
DESFLURANE inhalation anesthetics KCNA1
DESFLURANE inhalation anesthetics MT-ND1
DESIPRAMINE Antidepressive Agents, Tricyclic ADRB1
DESIPRAMINE Antidepressive Agents, Tricyclic ADRB2
DESIPRAMINE Antidepressive Agents, Tricyclic CHRM1
DESIPRAMINE Antidepressive Agents, Tricyclic CHRM2
DESIPRAMINE Antidepressive Agents, Tricyclic HRH1
DESIPRAMINE Antidepressive Agents, Tricyclic SLC6A2
DESIPRAMINE Antidepressive Agents, Tricyclic SLC6A4
DESLANOSIDE Antiarrhythmia Agents; Cardiotonic ATP1A1
Agents
DESOGESTREL Contraceptives, Oral ESR1
DESOGESTREL Contraceptives, Oral PGR
DESOXIMETASONE Anti-Inflammatory Agents; NR3C1
Glucocorticoids
DESOXYCORTICOSTERONE Hormone Replacement Agents, anti- NR3C2
PIVALATE addison agent
DEXBROMPHENIRAMINE Anti-Allergic Agents HRH1
DEXFENFLURAMINE Appetite Depressants SLC6A4
DEXMEDETOMIDINE Analgesics; Hypnotics and Sedatives ADRA2A
DEXTROMETHORPHAN Antitussive Agents GRIN3A
DEXTROMETHORPHAN Antitussive Agents OPRS1
DEZOCINE Analgesics, Opioid OPRK1
DEZOCINE Analgesics, Opioid OPRM1
DIAZOXIDE Antihypertensive Agents; SLC12A3
Vasodilator Agents
DIBUCAINE Anesthetics, Local SCN10A
DIBUCAINE Anesthetics, Local SCN5A
DICHLORPHENAMIDE Antiglaucomic Agents CA1
DICUMAROL Anticoagulants VKORC1
DICYCLOMINE Antispasmodics CHRM1
DIENESTROL Hormone Replacement Agents ESR1
DIETHYLPROPION Appetite Depressants SLC6A2
DIETHYLPROPION Appetite Depressants SLC6A3
DIETHYLSTILBESTROL Hormone Replacement Agents ESR1
DIFLORASONE Anti-Inflammatory Agents; NR3C1
Glucocorticoids
DIGITOXIN Anti-Arrhythmia Agents; ATP1A1
Cardiotonic Agents
DIGOXIN Anti-Arrhythmia Agents; ATP1A1
Cardiotonic Agents
DIHYDROTACHYSTEROL Anti-migraine Agents VDR
DIMENHYDRINATE Antiemetics HRH1
DINOPROST Abortifacient Agents PTGIR
TROMETHAMINE
DINOPROSTONE Abortifacient Agents PTGER1
DINOPROSTONE Abortifacient Agents PTGER2
DINOPROSTONE Abortifacient Agents PTGER3
DINOPROSTONE Abortifacient Agents PTGER4
DIPHEMANIL Bronchodilator Agents CHRM3
METHYLSULFATE
DIPHENHYDRAMINE Anti-Allergic Agents; Hypnotics and HRH1
sedatives; Antiemetics;
Antipruritics; Antitussives
DIPHENIDOL Antiemetics CHRM1
DIPHENIDOL Antiemetics CHRM2
DIPHENIDOL Antiemetics CHRM3
DIPHENOXYLATE Antidiarrheals OPRM1
DIPHENYLPYRALINE Anti-Allergic Agents HRH1
DIPIVEFRIN Ophthalmologicals ADRA2A
DISOPYRAMIDE Anti-Arrhythmia Agents SCN5A
DISULFIRAM Alcohol Deterrents ALDH2
DIVALPROEX SODIUM Anticonvulsants; Antimanic Agents ABAT
DOBUTAMINE Cardiotonic Agents ADRB1
DOFETILIDE Anti-Arrhythmia Agents KCNH2
DOFETILIDE Anti-Arrhythmia Agents KCNJ12
DOFETILIDE Anti-Arrhythmia Agents KCNK2
DOMPERIDONE Antiemetics DRD2
DOXACURIUM Muscle Relaxants CHRM2
DOXACURIUM Muscle Relaxants CHRNA2
DOXACURIUM CHLORIDE Muscle Relaxants CHRM2
DOXACURIUM CHLORIDE Muscle Relaxants CHRNA2
DOXAZOSIN Anticholesteremic Agents; ADRA1A
Antihypertensive Agents;
Vasodilator Agents
DOXAZOSIN Anticholesteremic Agents; ADRA1B
Antihypertensive Agents;
Vasodilator Agents
DOXAZOSIN Anticholesteremic Agents; ADRA1D
Antihypertensive Agents;
Vasodilator Agents
DOXYLAMINE Anti-Allergic Agents; Antiemetics; HRH1
Antitussive Agents; Hypnotics and
Sedatives
DROMOSTANOLONE Antineoplastic Agents, Hormonal AR
DRONEDARONE Anti-Arrhythmia Agents ADRA1A
DRONEDARONE Anti-Arrhythmia Agents ADRB1
DRONEDARONE Anti-Arrhythmia Agents KCNH2
DROPERIDOL Adjuvants, Anesthesia DRD2
DUTASTERIDE Anti-baldness Agents, SRD5A1
Antihyperplasia Agents
DUTASTERIDE Anti-baldness Agents, SRD5A2
Antihyperplasia Agents
DYCLONINE Anesthetics, Local SCN10A
DYDROGESTERONE Antidysmennorheal Agents PGR
DYPHYLLINE Bronchodilator Agents; Vasodilator PDE4A
Agents
DYPHYLLINE Bronchodilator Agents; Vasodilator PDE4B
Agents
DYPHYLLINE Bronchodilator Agents; Vasodilator PDE4C
Agents
DYPHYLLINE Bronchodilator Agents; Vasodilator PDE4D
Agents
DYPHYLLINE Bronchodilator Agents; Vasodilator PDE7A
Agents
DYPHYLLINE Bronchodilator Agents; Vasodilator PDE7B
Agents
ECHOTHIOPHATE IODIDE Miotics BCHE
EDROPHONIUM Anti-Arrhythmia Agents; Antidotes ACHE
EMEDASTINE Anti-Allergic Agents HRH1
ENCAINIDE Anti-Arrhythmia Agents SCN5A
ENFLURANE Anesthetics, Inhalation ATP2C1
ENFLURANE Anesthetics, Inhalation ATP5D
ENFLURANE Anesthetics, Inhalation GABRA1
ENFLURANE Anesthetics, Inhalation GLRA1
ENFLURANE Anesthetics, Inhalation GRIA1
ENFLURANE Anesthetics, Inhalation KCNA1
ENFLURANE Anesthetics, Inhalation KCNMA1
ENFLURANE Anesthetics, Inhalation MT-ND1
ENOXIMONE Cardiotonic Agents; Vasodilator PDE3A
Agents
ENPROFYLLINE Anti-Asthmatic Agents; PDE4A
Antiarrhythmic Agents;
Bronchodilator Agents
ENPROFYLLINE Anti-Asthmatic Agents; PDE4B
Antiarrhythmic Agents;
Bronchodilator Agents
EPHEDRINE Central Nervous System Stimulants ADRA1A
EPIRUBICIN Antineoplastic Agents CHD1
EPIRUBICIN Antineoplastic Agents TOP2A
EPOPROSTENOL Antihypertensive Agents; Platelet PTGIR
Aggregation Inhibitors
EPROSARTAN Antihypertensive Agents AGTR1
ERGOCALCIFEROL Antihypocalcemic Agents VDR
ERGOLOID MESYLATE Nootropic Agents; Vasodilator ADRA1A
Agents
ERGOLOID MESYLATE Nootropic Agents; Vasodilator ADRA2A
Agents
ERGOTAMINE Anti-migraine Agents HTR1B
ERGOTAMINE Anti-migraine Agents HTR1D
ERYTHRITYL Antianginal Agents; Vasodilator NPR1
TETRANITRATE Agents
ERYTHRITYL Antianginal Agents; Vasodilator NPR2
TETRANITRATE Agents
ESMOLOL Anti-Arrhythmia Agents ADRB1
ESTAZOLAM Anti-anxiety Agents; GABRA1
Anticonvulsants
ESTAZOLAM Anti-anxiety Agents; GABRA2
Anticonvulsants
ESTAZOLAM Anti-anxiety Agents; GABRA3
Anticonvulsants
ESTAZOLAM Anti-anxiety Agents; GABRA5
Anticonvulsants
ESTAZOLAM Anti-anxiety Agents; GABRB1
Anticonvulsants
ESTAZOLAM Anti-anxiety Agents; GABRB2
Anticonvulsants
ESTAZOLAM Anti-anxiety Agents; GABRB3
Anticonvulsants
ESTAZOLAM Anti-anxiety Agents; GABRD
Anticonvulsants
ESTAZOLAM Anti-anxiety Agents; GABRE
Anticonvulsants
ESTAZOLAM Anti-anxiety Agents; GABRG1
Anticonvulsants
ESTAZOLAM Anti-anxiety Agents; GABRG2
Anticonvulsants
ESTAZOLAM Anti-anxiety Agents; GABRG3
Anticonvulsants
ESTAZOLAM Anti-anxiety Agents; GABRP
Anticonvulsants
ESTAZOLAM Anti-anxiety Agents; GABRR1
Anticonvulsants
ESTAZOLAM Anti-anxiety Agents; GABRR2
Anticonvulsants
ESTAZOLAM Anti-anxiety Agents; GABRR3
Anticonvulsants
ESTRIOL Hormone Replacement Agents ESR1
ESTRONE Hormone Replacement Agents ESR1
ETHACRYNIC ACID Antihypertensive Agents; Diuretics SLC12A1
ETHOPROPAZINE Antidyskinetics CHRM1
ETHOSUXIMIDE Anticonvulsants CACNA1G
ETHOTOIN Anticonvulsants SCN5A
ETHOXZOLAMIDE Antihypertensive Agents, Diuretics; CA1
Antiglaucoma agents
ETHYNODIOL DIACETATE Contraceptives, Oral, Synthetic ESR1
ETHYNODIOL DIACETATE Contraceptives, Oral, Synthetic PGR
ETOMIDATE Anesthetics, Intravenous ADRA2B
ETOMIDATE Anesthetics, Intravenous GABRA1
ETOPOSIDE Antineoplastic Agents TOP2A
EZETIMIBE Anticholesteremic Agents NPC1L1
FELBAMATE Anticonvulsants; Antiepileptics GRIN2A
FELBAMATE Anticonvulsants; Antiepileptics GRIN2B
FELBAMATE Anticonvulsants; Antiepileptics GRIN3A
FENCAMFAMINE Central Nervous System Stimulants SLC6A3
FENOPROFEN NSAID PTGS1
FENOPROFEN NSAID PTGS2
FENOTEROL Bronchodilator Agents; Tocolytic ADRB2
Agents
FLAVOXATE Antispasmodics CHRM1
FLAVOXATE Antispasmodics CHRM2
FLECAINIDE Anti-Arrhythmia Agents SCN5A
FLUDIAZEPAM Anti-anxiety Agents; GABRA1
Anticonvulsants
FLUDIAZEPAM Anti-anxiety Agents; GABRA2
Anticonvulsants
FLUDIAZEPAM Anti-anxiety Agents; GABRA3
Anticonvulsants
FLUDIAZEPAM Anti-anxiety Agents; GABRA5
Anticonvulsants
FLUDIAZEPAM Anti-anxiety Agents; GABRB1
Anticonvulsants
FLUDIAZEPAM Anti-anxiety Agents; GABRB2
Anticonvulsants
FLUDIAZEPAM Anti-anxiety Agents; GABRB3
Anticonvulsants
FLUDIAZEPAM Anti-anxiety Agents; GABRD
Anticonvulsants
FLUDIAZEPAM Anti-anxiety Agents; GABRE
Anticonvulsants
FLUDIAZEPAM Anti-anxiety Agents; GABRG1
Anticonvulsants
FLUDIAZEPAM Anti-anxiety Agents; GABRG2
Anticonvulsants
FLUDIAZEPAM Anti-anxiety Agents; GABRG3
Anticonvulsants
FLUDIAZEPAM Anti-anxiety Agents; GABRP
Anticonvulsants
FLUDIAZEPAM Anti-anxiety Agents; GABRR1
Anticonvulsants
FLUDIAZEPAM Anti-anxiety Agents; GABRR2
Anticonvulsants
FLUDIAZEPAM Anti-anxiety Agents; GABRR3
Anticonvulsants
FLUDROCORTISONE Anti-Inflammatory Agents; NR3C2
corticosteroid
FLUMAZENIL Antidotes, Benzodoazepine GABRA1
Overdose
FLUMAZENIL Antidotes, Benzodoazepine GABRA2
Overdose
FLUMAZENIL Antidotes, Benzodoazepine GABRA3
Overdose
FLUMAZENIL Antidotes, Benzodoazepine GABRA5
Overdose
FLUMETHASONE PIVALATE Anti-Inflammatory Agents; NR3C1
corticosteroid
FLUNARIZINE Anticonvulsants; Vasodilator Agents CACNA1G
FLUNARIZINE Anticonvulsants; Vasodilator Agents CACNA1H
FLUNARIZINE Anticonvulsants; Vasodilator Agents CACNA1I
FLUNARIZINE Anticonvulsants; Vasodilator Agents HRH1
FLUNITRAZEPAM Hypnotics and Sedatives BZRP
FLUNITRAZEPAM Hypnotics and Sedatives GABRA2
FLUNITRAZEPAM Hypnotics and Sedatives GABRA3
FLUNITRAZEPAM Hypnotics and Sedatives GABRA4
FLUNITRAZEPAM Hypnotics and Sedatives GABRA5
FLUNITRAZEPAM Hypnotics and Sedatives GABRA6
FLUOROMETHOLONE Anti-Inflammatory Agents; Anti- NR3C1
allergic agents; Glucocorticoids
FLUOXYMESTERONE Anabolic Agents; Antineoplastic AR
Agents
FLUPENTHIXOL Antipsychotic Agents DRD1
FLUPENTHIXOL Antipsychotic Agents DRD2
FLUPHENAZINE Antipsychotic Agents DRD1
FLUPHENAZINE Antipsychotic Agents DRD2
FLURANDRENOLIDE Anti-Inflammatory Agents; NR3C1
Glucocorticoids
FLURAZEPAM Hypnotics and Sedatives GABRA1
FLURAZEPAM Hypnotics and Sedatives GABRA2
FLURAZEPAM Hypnotics and Sedatives GABRA3
FLURAZEPAM Hypnotics and Sedatives GABRA4
FLURAZEPAM Hypnotics and Sedatives GABRA5
FLURAZEPAM Hypnotics and Sedatives GABRA6
FLURAZEPAM Hypnotics and Sedatives GABRB1
FLURAZEPAM Hypnotics and Sedatives GABRB2
FLURAZEPAM Hypnotics and Sedatives GABRB3
FLURAZEPAM Hypnotics and Sedatives GABRD
FLURAZEPAM Hypnotics and Sedatives GABRE
FLURAZEPAM Hypnotics and Sedatives GABRG1
FLURAZEPAM Hypnotics and Sedatives GABRG2
FLURAZEPAM Hypnotics and Sedatives GABRG3
FLURAZEPAM Hypnotics and Sedatives GABRP
FLURAZEPAM Hypnotics and Sedatives GABRQ
FLURAZEPAM Hypnotics and Sedatives GABRR1
FLURAZEPAM Hypnotics and Sedatives GABRR2
FLURAZEPAM Hypnotics and Sedatives GABRR3
FLUSPIRILENE Antipsychotic Agents DRD2
FLUTAMIDE Antineoplastic Agents, Hormonal AR
FONDAPARINUX Antithrombotic Agents SERPINC1
FORASARTAN Antihypertensive Agents AGTR1
FOSINOPRIL Antihypertensive Agents ACE
FUROSEMIDE Antihypertensive Agents; Diuretics SLC12A1
GALLAMINE TRIETHIODIDE Muscle Relaxants, Skeletal CHRNA2
GEMFIBROZIL Antilipemic Agents PPARA
GLIBENCLAMIDE Hypoglycemic Agents KCNJ1
GLIBENCLAMIDE Hypoglycemic Agents KCNJ11
GLICLAZIDE Hypoglycemic Agents KCNJ1
GLIPIZIDE Hypoglycemic Agents KCNJ1
GLYCODIAZINE Hypoglycemic Agents KCNJ1
GONADORELIN Fertility Agents GNRHR
GONADORELIN Fertility Agents GNRHR2
GUANABENZ Antihypertensive Agents ADRA2A
GUANADREL SULFATE Antihypertensive Agents SLC6A2
GUANETHIDINE Antihypertensive Agents SLC6A2
HALAZEPAM Anti-anxiety Agents; Muscle GABRA1
Relaxants; Sedative
HALAZEPAM Anti-anxiety Agents; Muscle GABRA2
Relaxants; Sedative
HALAZEPAM Anti-anxiety Agents; Muscle GABRA3
Relaxants; Sedative
HALAZEPAM Anti-anxiety Agents; Muscle GABRA5
Relaxants; Sedative
HALAZEPAM Anti-anxiety Agents; Muscle GABRB1
Relaxants; Sedative
HALAZEPAM Anti-anxiety Agents; Muscle GABRB2
Relaxants; Sedative
HALAZEPAM Anti-anxiety Agents; Muscle GABRB3
Relaxants; Sedative
HALAZEPAM Anti-anxiety Agents; Muscle GABRD
Relaxants; Sedative
HALAZEPAM Anti-anxiety Agents; Muscle GABRE
Relaxants; Sedative
HALAZEPAM Anti-anxiety Agents; Muscle GABRG1
Relaxants; Sedative
HALAZEPAM Anti-anxiety Agents; Muscle GABRG2
Relaxants; Sedative
HALAZEPAM Anti-anxiety Agents; Muscle GABRG3
Relaxants; Sedative
HALAZEPAM Anti-anxiety Agents; Muscle GABRP
Relaxants; Sedative
HALAZEPAM Anti-anxiety Agents; Muscle GABRR1
Relaxants; Sedative
HALAZEPAM Anti-anxiety Agents; Muscle GABRR2
Relaxants; Sedative
HALAZEPAM Anti-anxiety Agents; Muscle GABRR3
Relaxants; Sedative
HALOBETASOL Anti-inflammatory Agents NR3C1
PROPIONATE
HALOPERIDOL Antipsychotic Agents DRD2
HALOTHANE Anesthetics, Inhalation ATP5D
HEXAFLURONIUM Muscle Relaxants BCHE
BROMIDE
HEXOBARBITAL Hypnotics and Sedatives CHRNA4
HEXOBARBITAL Hypnotics and Sedatives CHRNA7
HEXOBARBITAL Hypnotics and Sedatives GABRA1
HEXOBARBITAL Hypnotics and Sedatives GABRA2
HEXOBARBITAL Hypnotics and Sedatives GABRA3
HEXOBARBITAL Hypnotics and Sedatives GABRA4
HEXOBARBITAL Hypnotics and Sedatives GABRA5
HEXOBARBITAL Hypnotics and Sedatives GABRA6
HEXOBARBITAL Hypnotics and Sedatives GRIA2
HEXOBARBITAL Hypnotics and Sedatives GRIK2
HEXYLCAINE Anesthetics, Local SCN10A
HEXYLCAINE Anesthetics, Local SCN5A
HOMATROPINE GI Anti-Ulcer Agents, CHRM1
METHYLBROMIDE Antimuscarinics
HOMATROPINE GI Anti-Ulcer Agents, CHRM2
METHYLBROMIDE Antimuscarinics
HOMATROPINE GI Anti-Ulcer Agents, CHRM3
METHYLBROMIDE Antimuscarinics
HOMATROPINE GI Anti-Ulcer Agents, CHRM4
METHYLBROMIDE Antimuscarinics
HOMATROPINE GI Anti-Ulcer Agents, CHRM5
METHYLBROMIDE Antimuscarinics
HYDROCORTAMATE Anti-Inflammatory Agents; NR3C1
Glucocorticoids
HYDROCORTAMATE Anti-Inflammatory Agents; NR3C1
Glucocorticoids
HYDROFLUMETHIAZIDE Antihypertensive Agents; Diuretics SLC12A1
HYDROXYUREA Antineoplastic Agents RRM1
HYDROXYZINE Antipruritics; Anxiolytics sedatives HRH1
and hypnotics
IBUTILIDE Anti-Arrhythmia Agents CACNA1C
IBUTILIDE Anti-Arrhythmia Agents CACNA2D1
IBUTILIDE Anti-Arrhythmia Agents CACNB1
IBUTILIDE Anti-Arrhythmia Agents KCNH2
IDARUBICIN Antineoplastic Agents TOP2A
IFOSFAMIDE Antineoplastic Agents DNMT1
IMIPRAMINE Antidepressive Agents, Tricyclic SLC6A2
IMIPRAMINE Antidepressive Agents, Tricyclic SLC6A4
INDAPAMIDE Antihypertensive Agents; Diuretics KCNE1
INDAPAMIDE Antihypertensive Agents; Diuretics KCNQ1
INDECAINIDE Anti-Arrhythmia Agents SCN5A
ISOCARBOXAZID Antidepressive Agents MAOA
ISOCARBOXAZID Antidepressive Agents MAOB
ISOETHARINE Bronchodilator Agents ADRB1
ISOFLURANE Anesthetics, Inhalation ATP2C1
ISOFLURANE Anesthetics, Inhalation GABRA1
ISOFLURANE Anesthetics, Inhalation GLRA1
ISOFLURANE Anesthetics, Inhalation GRIA1
ISOFLURANE Anesthetics, Inhalation KCNA1
ISOFLUROPHATE Antiglaucomic Agents BCHE
ISOPROTERENOL Bronchodilator Agents; Cardiotonic ADRB1
Agents
ISOPROTERENOL Bronchodilator Agents; Cardiotonic ADRB2
Agents
ISOSORBIDE-5- Antianginal Agents; Vasodilator NPR1
MONONITRATE Agents
ISRADIPINE Antihypertensive Agents; CACNA1C
Vasodilator Agents
ISRADIPINE Antihypertensive Agents; CACNA2D1
Vasodilator Agents
LABETALOL Antihypertensive Agents ADRA1A
LABETALOL Antihypertensive Agents ADRA1B
LABETALOL Antihypertensive Agents ADRB1
LABETALOL Antihypertensive Agents ADRB2
LEFLUNOMIDE Antirheumatic Agents DHODH
LEVALLORPHAN Opiate Antagonists OPRM1
LEVOBUNOLOL Antiglaucomic Agents ADRB1
LEVOBUNOLOL Antiglaucomic Agents ADRB2
LEVOBUPIVACAINE Anesthetics, Local SCN10A
LEVOCABASTINE Anti-Allergic Agents HRH1
LEVOMETHADYL ACETATE Analgesics, Opioid OPRM1
LEVORPHANOL Analgesics, Opioid OPRM1
LIOTHYRONINE Hormone Replacement Agents THRA
LIOTHYRONINE Hormone Replacement Agents THRB
LISDEXAMFETAMINE Central Nervous System Stimulants ADRA1A
LISDEXAMFETAMINE Central Nervous System Stimulants ADRA1B
LISDEXAMFETAMINE Central Nervous System Stimulants SLC6A3
LISURIDE Antiparkinson Agents DRD1
LISURIDE Antiparkinson Agents DRD2
LISURIDE Antiparkinson Agents HTR1A
LOPERAMIDE Antidiarrheals OPRM1
LORAZEPAM Anti-anxiety Agents; BZRP
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRA1
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRA2
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRA3
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRA4
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRA5
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRA6
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRB1
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRB2
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRB3
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRD
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRE
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRG1
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRG2
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRG3
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRP
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRQ
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRR1
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRR2
Anticonvulsants; Hypnotics and
Sedatives
LORAZEPAM Anti-anxiety Agents; GABRR3
Anticonvulsants; Hypnotics and
Sedatives
LOSARTAN Antihypertensive Agents AGTR1
MAPROTILINE Antidepressive Agents, Second- SLC6A2
Generation
MARIMASTAT Antineoplastic Agents MMP2
MARIMASTAT Antineoplastic Agents MMP3
MARIMASTAT Antineoplastic Agents MMP9
MARINOL Antiemetics CNR1
MECLIZINE Antiemetics HRH1
MECLOFENAMIC ACID NSAID ALOX5
MECLOFENAMIC ACID NSAID PTGS1
MECLOFENAMIC ACID NSAID PTGS2
MEDRYSONE Anti-Inflammatory Agents, Topical NR3C1
MEFENAMIC ACID NSAID PTGS1
MEFENAMIC ACID NSAID PTGS2
MEGESTROL Antineoplastic Agents, Hormonal; ESR1
Contraceptives
MEGESTROL Antineoplastic Agents, Hormonal; PGR
Contraceptives
MELATONIN Hypnotics and Sedatives MTNR1A
MELATONIN Hypnotics and Sedatives MTNR1B
MELOXICAM NSAID PTGS2
MENTHOL Antipruritics TRPA1
MENTHOL Antipruritics TRPM8
MENTHOL Antipruritics TRPV3
MEPENZOLATE Antispasmodics GPR109A
MEPENZOLATE Antispasmodics GPR109B
MEPERIDINE Analgesics, Opioid OPRK1
MEPHENTERMINE Antihypotensive Agents; ADRA1A
Vasoconstrictor Agents
MEPHENYTOIN Anticonvulsants SCN5A
MEPROBAMATE Anticonvulsants; Hypnotics and GABRA1
Sedatives
MEPROBAMATE Anticonvulsants; Hypnotics and GABRA2
Sedatives
MEPROBAMATE Anticonvulsants; Hypnotics and GABRA3
Sedatives
MEPROBAMATE Anticonvulsants; Hypnotics and GABRA4
Sedatives
MEPROBAMATE Anticonvulsants; Hypnotics and GABRA5
Sedatives
MEPROBAMATE Anticonvulsants; Hypnotics and GABRA6
Sedatives
MEQUITAZINE Anti-Allergic Agents HRH1
MERCAPTOPURINE Antineoplastic Agents HPRT1
MESORIDAZINE Antipsychotic Agents DRD2
MESORIDAZINE Antipsychotic Agents HTR2A
MESTRANOL Contraceptives, Oral ESR1
METARAMINOL Antihypotensive Agents; ADRA1A
Vasoconstrictor Agents
METHADONE Analgesics, Opioid; Antitussive OPRM1
Agents
METHADYL ACETATE Analgesics, Opioid OPRM1
METHANTHELINE GI Anti-Ulcer Agents, CHRM1
anticholinergic; Antispasmodics
METHARBITAL Anticonvulsants CHRNA4
METHARBITAL Anticonvulsants CHRNA7
METHARBITAL Anticonvulsants GABRA1
METHARBITAL Anticonvulsants GABRA2
METHARBITAL Anticonvulsants GABRA3
METHARBITAL Anticonvulsants GABRA4
METHARBITAL Anticonvulsants GABRA5
METHARBITAL Anticonvulsants GABRA6
METHARBITAL Anticonvulsants GRIA2
METHARBITAL Anticonvulsants GRIK2
METHAZOLAMIDE Antihypertensive Agents, Diuretics; CA1
Antiglaucoma agents
METHDILAZINE Anti-Allergic Agents HRH1
METHIMAZOLE Antithyroid Agents TPO
METHOHEXITAL Anesthetics, Intravenous GABRA1
METHOTRIMEPRAZINE Antipsychotic Agents ADRA1A
METHOTRIMEPRAZINE Antipsychotic Agents ADRA1B
METHOTRIMEPRAZINE Antipsychotic Agents ADRA1D
METHOTRIMEPRAZINE Antipsychotic Agents CHRM1
METHOTRIMEPRAZINE Antipsychotic Agents CHRM2
METHOTRIMEPRAZINE Antipsychotic Agents CHRM3
METHOTRIMEPRAZINE Antipsychotic Agents CHRM4
METHOTRIMEPRAZINE Antipsychotic Agents CHRM5
METHOTRIMEPRAZINE Antipsychotic Agents DRD3
METHOTRIMEPRAZINE Antipsychotic Agents HRH1
METHOTRIMEPRAZINE Antipsychotic Agents HTR2B
METHOXAMINE Antihypotensive Agents; ADRA1A
Vasoconstrictor Agents
METHOXAMINE Antihypotensive Agents; ADRA1B
Vasoconstrictor Agents
METHOXYFLURANE Anesthetics, Inhalation ATP5D
METHYCLOTHIAZIDE Antihypertensive Agents; Diuretics SLC12A1
METHYLDOPA Antihypertensive Agents ADRA2A
METHYLERGONOVINE Abortifacient Agents DRD1
METHYLNALTREXONE OIC treatment OPRM1
BROMIDE
METHYLPHENOBARBITAL Anticonvulsants; Hypnotics and CHRNA4
Sedatives
METHYLPHENOBARBITAL Anticonvulsants; Hypnotics and CHRNA7
Sedatives
METHYLPHENOBARBITAL Anticonvulsants; Hypnotics and GABRA1
Sedatives
METHYLPHENOBARBITAL Anticonvulsants; Hypnotics and GABRA2
Sedatives
METHYLPHENOBARBITAL Anticonvulsants; Hypnotics and GABRA3
Sedatives
METHYLPHENOBARBITAL Anticonvulsants; Hypnotics and GABRA4
Sedatives
METHYLPHENOBARBITAL Anticonvulsants; Hypnotics and GABRA5
Sedatives
METHYLPHENOBARBITAL Anticonvulsants; Hypnotics and GABRA6
Sedatives
METHYLPHENOBARBITAL Anticonvulsants; Hypnotics and GRIA2
Sedatives
METHYLPHENOBARBITAL Anticonvulsants; Hypnotics and GRIK2
Sedatives
METHYLPREDNISOLONE Anti-Inflammatory Agents; NR3C1
Glucocorticoids
METHYLPREDNISOLONE Anti-Inflammatory Agents; NR3C1
Glucocorticoids
METHYLSCOPOLAMINE Antispasmodics CHRM1
METHYPRYLON Hypnotics and Sedatives GABRA1
METHYSERGIDE Anti-migraine agents; HTR1A
Vasoconstrictor Agents
METHYSERGIDE Anti-migraine agents; HTR2A
Vasoconstrictor Agents
METHYSERGIDE Anti-migraine agents; HTR2C
Vasoconstrictor Agents
METHYSERGIDE Anti-migraine agents; HTR7
Vasoconstrictor Agents
METIPRANOLOL Anti-Arrhythmia Agents; ADRB1
Antihypertensive Agents; Anti-
glaucoma agent
METIPRANOLOL Anti-Arrhythmia Agents; ADRB2
Antihypertensive Agents; Anti-
glaucoma agent
METIXENE Antiparkinson Agents CHRM1
METIXENE Antiparkinson Agents CHRM2
METIXENE Antiparkinson Agents CHRM3
METIXENE Antiparkinson Agents CHRM4
METIXENE Antiparkinson Agents CHRM5
METOCURINE Muscle Relaxants CHRNA2
METOCURINE IODIDE Muscle Relaxants CHRNA2
METOLAZONE Antihypertensive Agents; Diuretics SLC12A1
METOLAZONE Antihypertensive Agents; Diuretics SLC12A3
METOPROLOL Anti-Arrhythmia Agents; ADRB1
Antihypertensive Agents
METYRAPONE Diagnostic Agents CYP11B1
METYROSINE Catecholamine synthesis inhibitors TH
MEXILETINE Anti-Arrhythmia Agents SCN5A
MIANSERIN Antidepressive Agents, Second- ADRA2A
Generation
MIANSERIN Antidepressive Agents, Second- HRH1
Generation
MIANSERIN Antidepressive Agents, Second- HTR2A
Generation
MIANSERIN Antidepressive Agents, Second- HTR2C
Generation
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRA1
and Sedatives
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRA2
and Sedatives
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRA3
and Sedatives
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRA4
and Sedatives
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRA5
and Sedatives
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRA6
and Sedatives
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRB1
and Sedatives
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRB2
and Sedatives
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRB3
and Sedatives
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRD
and Sedatives
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRE
and Sedatives
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRG1
and Sedatives
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRG2
and Sedatives
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRG3
and Sedatives
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRP
and Sedatives
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRQ
and Sedatives
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRR1
and Sedatives
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRR2
and Sedatives
MIDAZOLAM Adjuvants, Anesthesia; Hypnotics GABRR3
and Sedatives
MIDODRINE Antihypotensive Agents; ADRA1A
Vasoconstrictor Agents
MIDODRINE Antihypotensive Agents; ADRA1B
Vasoconstrictor Agents
MIGLITOL Hypoglycemic Agents MGAM
MILRINONE Cardiotonic Agents; Vasodilator PDE3A
Agents
MILRINONE Cardiotonic Agents; Vasodilator PDE4A
Agents
MINAPRINE Antidepressive Agents DRD1
MINAPRINE Antidepressive Agents DRD2
MINAPRINE Antidepressive Agents HTR2A
MINAPRINE Antidepressive Agents HTR2B
MINAPRINE Antidepressive Agents HTR2C
MINAPRINE Antidepressive Agents SLC6A4
MINOXIDIL Antihypertensive Agents; KCNJ1
Vasodilator Agents
MIVACURIUM Muscle Relaxants CHRM2
MIVACURIUM Muscle Relaxants CHRNA2
MOEXIPRIL Antihypertensive Agents ACE
MOLINDONE Antipsychotic Agents DRD2
MORICIZINE Anti-Arrhythmia Agents SCN5A
NABUMETONE Anti-Inflammatory Agents, Non- PTGS1
Steroidal
NABUMETONE Anti-Inflammatory Agents, Non- PTGS2
Steroidal
NADOLOL Anti-Arrhythmia Agents; ADRB1
Antihypertensive Agents
NADOLOL Anti-Arrhythmia Agents; ADRB2
Antihypertensive Agents
NAFARELIN Antiendometriosis Agent GNRHR
NAFARELIN Antiendometriosis Agent GNRHR2
NANDROLONE Antianemic Agents; anti- AR
osteoporosis agents
NEDOCROMIL Anti-Allergic Agents; Anti- CYSLTR1
Asthmatic Agents
NEFAZODONE Antidepressive Agents, Second- ADRA1A
Generation
NEFAZODONE Antidepressive Agents, Second- ADRA1B
Generation
NEFAZODONE Antidepressive Agents, Second- HTR2A
Generation
NEFAZODONE Antidepressive Agents, Second- SLC6A2
Generation
NEFAZODONE Antidepressive Agents, Second- SLC6A4
Generation
NEOSTIGMINE Parasympathomimetics ACHE
NEPAFENAC NSAID PTGS1
NEPAFENAC NSAID PTGS2
NICARDIPINE Anti-Arrhythmia Agents; CACNA1C
Antihypertensive Agents
NICERGOLINE Nootropic Agents; Vasodilator ADRA1A
Agents
NICOTINE Central Nervous System Stimulants CHRNA10
NICOTINE Central Nervous System Stimulants CHRNA2
NICOTINE Central Nervous System Stimulants CHRNA4
NICOTINE Central Nervous System Stimulants CHRNA7
NICOTINE Central Nervous System Stimulants CHRNA9
NICOTINE Central Nervous System Stimulants CHRNB2
NIFEDIPINE Antianginal Agents; Vasodilator CACNA2D1
Agents
NIFLUMIC ACID NSAID PLA2G1B
NIFLUMIC ACID NSAID PTGS2
NILUTAMIDE Antineoplastic Agents AR
NIMODIPINE Antihypertensive Agents; CACNG1
Vasodilator Agents
NISOLDIPINE Antihypertensive Agents; CACNA1A
Vasodilator Agents
NITRAZEPAM Anticonvulsants; Hypnotics and GABRA1
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and GABRA2
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and GABRA3
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and GABRA4
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and GABRA5
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and GABRA6
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and GABRB1
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and GABRB2
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and GABRB3
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and GABRD
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and GABRE
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and GABRG1
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and GABRG2
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and GABRG3
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and GABRP
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and GABRQ
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and GABRR1
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and GABRR2
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and GABRR3
Sedatives
NITRAZEPAM Anticonvulsants; Hypnotics and SCN1A
Sedatives
NITRENDIPINE Antihypertensive Agents; CACNG1
Vasodilator Agents
NITROPRUSSIDE Antihypertensive Agents; NPR1
Vasodilator Agents
NIZATIDINE GI Anti-Ulcer Agents, HRH2
antihistamines
NOREPINEPHRINE Antihypotensive Agents; ADRA1A
Vasoconstrictor Agents
NOREPINEPHRINE Antihypotensive Agents; ADRA1B
Vasoconstrictor Agents
NOREPINEPHRINE Antihypotensive Agents; ADRA1D
Vasoconstrictor Agents
NOREPINEPHRINE Antihypotensive Agents; ADRA2A
Vasoconstrictor Agents
NOREPINEPHRINE Antihypotensive Agents; ADRA2B
Vasoconstrictor Agents
NOREPINEPHRINE Antihypotensive Agents; ADRA2C
Vasoconstrictor Agents
NORETHINDRONE Contraceptives, Oral, Synthetic PGR
NORGESTIMATE Contraceptives, Oral, Synthetic ESR1
NORGESTIMATE Contraceptives, Oral, Synthetic PGR
NORGESTREL Contraceptives, Oral, Synthetic ESR1
NORGESTREL Contraceptives, Oral, Synthetic PGR
ORCIPRENALINE Bronchodilator Agents ADRB2
ORPHENADRINE Antiparkinson Agents; Muscle GRIN1
Relaxants, Central
ORPHENADRINE Antiparkinson Agents; Muscle GRIN2D
Relaxants, Central
ORPHENADRINE Antiparkinson Agents; Muscle GRIN3A
Relaxants, Central
ORPHENADRINE Antiparkinson Agents; Muscle GRIN3B
Relaxants, Central
ORPHENADRINE Antiparkinson Agents; Muscle HRH1
Relaxants, Central
OUABAIN Cardiotonic Agents ATP1A1
OXAPROZIN NSAID PTGS2
OXAZEPAM Hypnotics and Sedatives GABRA1
OXAZEPAM Hypnotics and Sedatives GABRA2
OXAZEPAM Hypnotics and Sedatives GABRA3
OXAZEPAM Hypnotics and Sedatives GABRA4
OXAZEPAM Hypnotics and Sedatives GABRA5
OXAZEPAM Hypnotics and Sedatives GABRA6
OXAZEPAM Hypnotics and Sedatives GABRB1
OXAZEPAM Hypnotics and Sedatives GABRB2
OXAZEPAM Hypnotics and Sedatives GABRB3
OXAZEPAM Hypnotics and Sedatives GABRD
OXAZEPAM Hypnotics and Sedatives GABRE
OXAZEPAM Hypnotics and Sedatives GABRG1
OXAZEPAM Hypnotics and Sedatives GABRG2
OXAZEPAM Hypnotics and Sedatives GABRG3
OXAZEPAM Hypnotics and Sedatives GABRP
OXAZEPAM Hypnotics and Sedatives GABRQ
OXAZEPAM Hypnotics and Sedatives GABRR1
OXAZEPAM Hypnotics and Sedatives GABRR2
OXAZEPAM Hypnotics and Sedatives GABRR3
OXPRENOLOL Antihypertensive Agents; Anti- ADRB1
Arrhythmia Agents
OXPRENOLOL Antihypertensive Agents; Anti- ADRB2
Arrhythmia Agents
OXYBUPROCAINE Anesthetics, Local SCN10A
OXYPHENCYCLIMINE GI Anti-Ulcer Agents, CHRM1
anticholinergic; Antispasmodics
OXYPHENCYCLIMINE GI Anti-Ulcer Agents, CHRM2
anticholinergic; Antispasmodics
OXYPHENCYCLIMINE GI Anti-Ulcer Agents, CHRM3
anticholinergic; Antispasmodics
OXYPHENONIUM Mydriatics CHRM1
PAMIDRONATE Bisphosphonates FDPS
PANCURONIUM Muscle Relaxants CHRNA2
PAPAVERINE Antispasmodics; Anti-impotence PDE4B
Agents; Vasodilator Agents
PARAMETHADIONE Anticonvulsants CACNA1I
PARAMETHASONE Anti-Inflammatory Agents; NR3C1
Glucocorticoids
PEMETREXED Antineoplastic Agents DHFR
PEMETREXED Antineoplastic Agents GART
PEMETREXED Antineoplastic Agents TYMS
PEMIROLAST Anti-Allergic Agents HRH1
PENBUTOLOL Antihypertensive Agents ADRB1
PENBUTOLOL Antihypertensive Agents ADRB2
PENTAGASTRIN Diagnostic Agents CCKBR
PENTAZOCINE Analgesics, Opioid OPRK1
PENTAZOCINE Analgesics, Opioid OPRM1
PENTOBARBITAL Hypnotics and Sedatives CHRNA4
PENTOBARBITAL Hypnotics and Sedatives CHRNA7
PENTOBARBITAL Hypnotics and Sedatives GABRA1
PENTOBARBITAL Hypnotics and Sedatives GABRA2
PENTOBARBITAL Hypnotics and Sedatives GABRA3
PENTOBARBITAL Hypnotics and Sedatives GABRA4
PENTOBARBITAL Hypnotics and Sedatives GABRA5
PENTOBARBITAL Hypnotics and Sedatives GABRA6
PENTOBARBITAL Hypnotics and Sedatives GRIA2
PENTOBARBITAL Hypnotics and Sedatives GRIK2
PENTOLINIUM Antihypertensive Agents CHRNA10
PERGOLIDE Antiparkinson Agents DRD1
PERGOLIDE Antiparkinson Agents DRD2
PERHEXILINE Antianginal Agents; Vasodilator CPT1A
Agents
PERHEXILINE Antianginal Agents; Vasodilator CPT2
Agents
PERINDOPRIL Antihypertensive Agents ACE
PERPHENAZINE Antipsychotic Agents DRD1
PERPHENAZINE Antipsychotic Agents DRD2
PHENACEMIDE Anticonvulsants SCN1A
PHENDIMETRAZINE Appetite Depressants ADRA1A
PHENDIMETRAZINE Appetite Depressants ADRA1B
PHENELZINE Antidepressive Agents MAOA
PHENELZINE Antidepressive Agents MAOB
PHENFORMIN Hypoglycemic Agents PRKAA1
PHENINDIONE Anticoagulants VKORC1
PHENIRAMINE Anti-Allergic Agents HRH1
PHENMETRAZINE Appetite Depressants SLC6A2
PHENMETRAZINE Appetite Depressants SLC6A3
PHENOBARBITAL Anticonvulsants; Hypnotics and CHRNA4
Sedatives
PHENOBARBITAL Anticonvulsants; Hypnotics and CHRNA7
Sedatives
PHENOBARBITAL Anticonvulsants; Hypnotics and GABRA1
Sedatives
PHENOBARBITAL Anticonvulsants; Hypnotics and GABRA2
Sedatives
PHENOBARBITAL Anticonvulsants; Hypnotics and GABRA3
Sedatives
PHENOBARBITAL Anticonvulsants; Hypnotics and GABRA4
Sedatives
PHENOBARBITAL Anticonvulsants; Hypnotics and GABRA5
Sedatives
PHENOBARBITAL Anticonvulsants; Hypnotics and GABRA6
Sedatives
PHENOBARBITAL Anticonvulsants; Hypnotics and GRIA1
Sedatives
PHENOBARBITAL Anticonvulsants; Hypnotics and GRIA2
Sedatives
PHENOBARBITAL Anticonvulsants; Hypnotics and GRIK2
Sedatives
PHENOXYBENZAMINE Anticonvulsants; Hypnotics and ADRA1A
Sedatives
PHENPROCOUMON Anticoagulants VKORC1
PHENTERMINE Appetite Depressants SLC6A2
PHENTERMINE Appetite Depressants SLC6A3
PHENTERMINE Appetite Depressants SLC6A4
PHENTOLAMINE Antihypertensive Agents ADRA2A
PHENYLBUTAZONE NSAID PTGIS
PHENYLBUTAZONE NSAID PTGS2
PHENYLPROPANOLAMINE Appetite Depressants; Nasal ADRA1A
Decongestants
PHENYLPROPANOLAMINE Appetite Depressants; Nasal ADRA2A
Decongestants
PHENYTOIN Anticonvulsants SCN1A
PHENYTOIN Anticonvulsants SCN5A
PHYTONADIONE Antifibrinolytic Agents GGCX
PICROTOXIN Central Nervous System Stimulants; GABRA1
Convulsants
PICROTOXIN Central Nervous System Stimulants; GABRR1
Convulsants
PIMOZIDE Antidyskinetics; Antipsychotic DRD2
Agents
PINDOLOL Antihypertensive Agents ADRB1
PINDOLOL Antihypertensive Agents ADRB2
PIPECURONIUM Muscle Relaxants CHRNA2
PIRENZEPINE GI Anti-Ulcer Agents, CHRM1
anticholinergic; Antispasmodics
PODOFILOX Antineoplastic Agents, Phytogenic; TOP2A
Keratolytic Agents
POLYTHIAZIDE Antihypertensive Agents; Diuretics SLC12A3
PRACTOLOL Anti-Arrhythmia Agents ADRB1
PRALATREXATE Antineoplastic Agents DHFR
PRANLUKAST Anti-Asthmatic Agents CYSLTR1
PRAZEPAM Anti-anxiety Agents; Hypnotics and GABRA1
Sedatives
PRAZEPAM Anti-anxiety Agents; Hypnotics and GABRA2
Sedatives
PRAZEPAM Anti-anxiety Agents; Hypnotics and GABRA3
Sedatives
PRAZEPAM Anti-anxiety Agents; Hypnotics and GABRA5
Sedatives
PRAZEPAM Anti-anxiety Agents; Hypnotics and GABRB1
Sedatives
PRAZEPAM Anti-anxiety Agents; Hypnotics and GABRB2
Sedatives
PRAZEPAM Anti-anxiety Agents; Hypnotics and GABRB3
Sedatives
PRAZEPAM Anti-anxiety Agents; Hypnotics and GABRD
Sedatives
PRAZEPAM Anti-anxiety Agents; Hypnotics and GABRE
Sedatives
PRAZEPAM Anti-anxiety Agents; Hypnotics and GABRG1
Sedatives
PRAZEPAM Anti-anxiety Agents; Hypnotics and GABRG2
Sedatives
PRAZEPAM Anti-anxiety Agents; Hypnotics and GABRG3
Sedatives
PRAZEPAM Anti-anxiety Agents; Hypnotics and GABRP
Sedatives
PRAZEPAM Anti-anxiety Agents; Hypnotics and GABRR1
Sedatives
PRAZEPAM Anti-anxiety Agents; Hypnotics and GABRR2
Sedatives
PRAZEPAM Anti-anxiety Agents; Hypnotics and GABRR3
Sedatives
PRAZOSIN Antihypertensive Agents; ADRA1A
antispasmodics
PRAZOSIN Antihypertensive Agents; ADRA1B
antispasmodics
PRAZOSIN Antihypertensive Agents; ADRA1D
antispasmodics
PREDNICARBATE Anti-Inflammatory Agents; NR3C1
Corticosteroids
PRIMIDONE Anticonvulsants CHRNA4
PRIMIDONE Anticonvulsants CHRNA7
PRIMIDONE Anticonvulsants GABRA1
PRIMIDONE Anticonvulsants GABRA2
PRIMIDONE Anticonvulsants GABRA3
PRIMIDONE Anticonvulsants GABRA4
PRIMIDONE Anticonvulsants GABRA5
PRIMIDONE Anticonvulsants GABRA6
PRIMIDONE Anticonvulsants GRIA2
PRIMIDONE Anticonvulsants GRIK2
PROBENECID Uricosuric Agents SLC22A11
PROBENECID Uricosuric Agents SLC22A8
PROCAINAMIDE Anti-Arrhythmia Agents SCN5A
PROCAINE Anesthetics, Local SCN10A
PROCATEROL Bronchodilator Agents ADRB2
PROCYCLIDINE Antidyskinetics; Antiparkinson CHRM1
Agents
PROCYCLIDINE Antidyskinetics; Antiparkinson CHRM2
Agents
PROCYCLIDINE Antidyskinetics; Antiparkinson CHRM4
Agents
PROGABIDE Anticonvulsants GABBR1
PROGABIDE Anticonvulsants GABRA1
PROMAZINE Antiemetics; Antipsychotic Agents ADRA1A
PROMAZINE Antiemetics; Antipsychotic Agents ADRA1B
PROMAZINE Antiemetics; Antipsychotic Agents ADRA1D
PROMAZINE Antiemetics; Antipsychotic Agents CHRM1
PROMAZINE Antiemetics; Antipsychotic Agents CHRM2
PROMAZINE Antiemetics; Antipsychotic Agents CHRM3
PROMAZINE Antiemetics; Antipsychotic Agents CHRM4
PROMAZINE Antiemetics; Antipsychotic Agents CHRM5
PROMAZINE Antiemetics; Antipsychotic Agents DRD1
PROMAZINE Antiemetics; Antipsychotic Agents DRD2
PROMAZINE Antiemetics; Antipsychotic Agents DRD4
PROMAZINE Antiemetics; Antipsychotic Agents HRH1
PROMAZINE Antiemetics; Antipsychotic Agents HTR2A
PROMAZINE Antiemetics; Antipsychotic Agents HTR2C
PROMETHAZINE Hypnotics and Sedatives; Anti- CHRM1
anxiety agents; Anti-allergic Agents
PROMETHAZINE Hypnotics and Sedatives; Anti- CHRM2
anxiety agents; Anti-allergic Agents
PROMETHAZINE Hypnotics and Sedatives; Anti- CHRM3
anxiety agents; Anti-allergic Agents
PROMETHAZINE Hypnotics and Sedatives; Anti- CHRM4
anxiety agents; Anti-allergic Agents
PROMETHAZINE Hypnotics and Sedatives; Anti- CHRM5
anxiety agents; Anti-allergic Agents
PROMETHAZINE Hypnotics and Sedatives; Anti- HRH1
anxiety agents; Anti-allergic Agents
PROPANTHELINE GI Anti-Ulcer Agents, CHRM1
anticholinergic; Antispasmodics
PROPARACAINE Anesthetics, Local SCN10A
PROPERICIAZINE Antipsychotic Agents ADRA1A
PROPERICIAZINE Antipsychotic Agents ADRA1B
PROPERICIAZINE Antipsychotic Agents ADRA1D
PROPIOMAZINE Hypnotics and Sedatives ADRA1A
PROPIOMAZINE Hypnotics and Sedatives ADRA1B
PROPIOMAZINE Hypnotics and Sedatives ADRA1D
PROPIOMAZINE Hypnotics and Sedatives CHRM1
PROPIOMAZINE Hypnotics and Sedatives CHRM2
PROPIOMAZINE Hypnotics and Sedatives CHRM3
PROPIOMAZINE Hypnotics and Sedatives CHRM4
PROPIOMAZINE Hypnotics and Sedatives CHRM5
PROPIOMAZINE Hypnotics and Sedatives DRD1
PROPIOMAZINE Hypnotics and Sedatives DRD2
PROPIOMAZINE Hypnotics and Sedatives DRD4
PROPIOMAZINE Hypnotics and Sedatives HRH1
PROPIOMAZINE Hypnotics and Sedatives HTR2A
PROPIOMAZINE Hypnotics and Sedatives HTR2C
PROPOXYPHENE Analgesics, Opioid; Antitussive OPRD1
Agents
PROPOXYPHENE Analgesics, Opioid; Antitussive OPRK1
Agents
PROPOXYPHENE Analgesics, Opioid; Antitussive OPRM1
Agents
PROPYLTHIOURACIL Antithyroid Agents TPO
PROTRIPTYLINE Antidepressive Agents, Tricyclic SLC6A2
PROTRIPTYLINE Antidepressive Agents, Tricyclic SLC6A4
PYRIDOSTIGMINE Antimyasthenics ACHE
QUAZEPAM Hypnotics and Sedatives GABRA1
QUAZEPAM Hypnotics and Sedatives GABRA2
QUAZEPAM Hypnotics and Sedatives GABRA3
QUAZEPAM Hypnotics and Sedatives GABRA5
QUAZEPAM Hypnotics and Sedatives GABRB1
QUAZEPAM Hypnotics and Sedatives GABRB3
QUAZEPAM Hypnotics and Sedatives GABRD
QUAZEPAM Hypnotics and Sedatives GABRE
QUAZEPAM Hypnotics and Sedatives GABRG1
QUAZEPAM Hypnotics and Sedatives GABRG2
QUAZEPAM Hypnotics and Sedatives GABRG3
QUAZEPAM Hypnotics and Sedatives GABRP
QUAZEPAM Hypnotics and Sedatives GABRR1
QUAZEPAM Hypnotics and Sedatives GABRR2
QUAZEPAM Hypnotics and Sedatives GABRR3
QUINESTROL Hormone Replacement Agents ESR1
QUINETHAZONE Antihypertensive Agents; Diuretics SLC12A3
QUINIDINE Anti-Arrhythmia Agents SCN5A
RALOXIFENE Hormone Replacement Agents ESR1
RALOXIFENE Hormone Replacement Agents ESR2
RAMIPRIL Antihypertensive Agents ACE
REMIKIREN Antihypertensive Agents REN
REMOXIPRIDE Antipsychotic Agents DRD2
RESCINNAMINE Antihypertensive Agents ACE
RESERPINE Antihypertensive Agents; SLC18A2
Antipsychotic Agents
RIMEXOLONE Anti-Inflammatory Agents; NR3C1
Corticosteroids
RIMEXOLONE Anti-Inflammatory Agents; NR3C1
Corticosteroids
RISEDRONATE Bisphosphonates FDPS
RISPERIDONE Antipsychotic Agents DRD2
RISPERIDONE Antipsychotic Agents HTR2A
RITODRINE Tocolytic Agents ADRB2
RIZATRIPTAN Anti-migraine Agents HTR1B
RIZATRIPTAN Anti-migraine Agents HTR1D
SALICYLIC ACID Keratolytic Agents PTGS1
SALICYLIC ACID Keratolytic Agents PTGS2
SALSALATE Anti-Inflammatory Agents, Non- PTGS1
Steroidal
SALSALATE Anti-Inflammatory Agents, Non- PTGS2
Steroidal
SAPRISARTAN Antihypertensive Agents AGTR1
SAPROPTERIN PKU-treatment PAH
SCOPOLAMINE Adjuvants, Anesthesia; CHRM1
Antispasmodics; Mydriatics
SECOBARBITAL Adjuvants, anesthesia; Hypnotics CHRNA4
and Sedatives
SECOBARBITAL Adjuvants, anesthesia; Hypnotics CHRNA7
and Sedatives
SECOBARBITAL Adjuvants, anesthesia; Hypnotics GABRA1
and Sedatives
SECOBARBITAL Adjuvants, anesthesia; Hypnotics GABRA2
and Sedatives
SECOBARBITAL Adjuvants, anesthesia; Hypnotics GABRA3
and Sedatives
SECOBARBITAL Adjuvants, anesthesia; Hypnotics GABRA4
and Sedatives
SECOBARBITAL Adjuvants, anesthesia; Hypnotics GABRA5
and Sedatives
SECOBARBITAL Adjuvants, anesthesia; Hypnotics GABRA6
and Sedatives
SECOBARBITAL Adjuvants, anesthesia; Hypnotics GRIA2
and Sedatives
SECOBARBITAL Adjuvants, anesthesia; Hypnotics GRIK2
and Sedatives
SEVOFLURANE Anesthetics, Inhalation ATP2C1
SEVOFLURANE Anesthetics, Inhalation ATP5D
SEVOFLURANE Anesthetics, Inhalation GABRA1
SEVOFLURANE Anesthetics, Inhalation GLRA1
SEVOFLURANE Anesthetics, Inhalation GRIA1
SEVOFLURANE Anesthetics, Inhalation KCNA1
SEVOFLURANE Anesthetics, Inhalation MT-ND1
SODIUM TETRADECYL Sclerosing Agents PROC
SULFATE
SOTALOL Anti-Arrhythmia Agents KCNH2
SPIRAPRIL Antihypertensive Agents ACE
SUCCINYLCHOLINE Muscle Relaxants, Skeletal CHRM1
SULFINPYRAZONE Uricosuric Agents ABCC1
SULFINPYRAZONE Uricosuric Agents ABCC2
SULINDAC NSAID PTGS1
SULINDAC NSAID PTGS2
SULPIRIDE Antidepressive Agents, Second- DRD2
Generation; Antipsychotic Agents
SUPROFEN NSAID PTGS1
SUPROFEN NSAID PTGS2
TACRINE Nootropic Agents ACHE
TALBUTAL Analgesics CHRNA4
TALBUTAL Analgesics CHRNA7
TALBUTAL Analgesics GABRA1
TALBUTAL Analgesics GABRA2
TALBUTAL Analgesics GABRA3
TALBUTAL Analgesics GABRA4
TALBUTAL Analgesics GABRA5
TALBUTAL Analgesics GABRA6
TALBUTAL Analgesics GRIA2
TALBUTAL Analgesics GRIK2
TAMOXIFEN Antineoplastic Agents, Hormonal ESR1
TAMOXIFEN Antineoplastic Agents, Hormonal ESR2
TASOSARTAN Antihypertensive Agents AGTR1
TEMAZEPAM Hypnotics and Sedatives BZRP
TEMAZEPAM Hypnotics and Sedatives GABRA1
TEMAZEPAM Hypnotics and Sedatives GABRA2
TEMAZEPAM Hypnotics and Sedatives GABRA3
TEMAZEPAM Hypnotics and Sedatives GABRA4
TEMAZEPAM Hypnotics and Sedatives GABRA5
TEMAZEPAM Hypnotics and Sedatives GABRA6
TEMAZEPAM Hypnotics and Sedatives GABRB1
TEMAZEPAM Hypnotics and Sedatives GABRB2
TEMAZEPAM Hypnotics and Sedatives GABRB3
TEMAZEPAM Hypnotics and Sedatives GABRD
TEMAZEPAM Hypnotics and Sedatives GABRE
TEMAZEPAM Hypnotics and Sedatives GABRG1
TEMAZEPAM Hypnotics and Sedatives GABRG2
TEMAZEPAM Hypnotics and Sedatives GABRG3
TEMAZEPAM Hypnotics and Sedatives GABRP
TEMAZEPAM Hypnotics and Sedatives GABRQ
TEMAZEPAM Hypnotics and Sedatives GABRR1
TEMAZEPAM Hypnotics and Sedatives GABRR2
TEMAZEPAM Hypnotics and Sedatives GABRR3
TENIPOSIDE Antineoplastic Agents TOP2A
TENOXICAM NSAID PTGS1
TENOXICAM NSAID PTGS2
TERAZOSIN Antineoplastic Agents; ADRA1A
antihypertensive agents
TERAZOSIN Antineoplastic Agents; ADRA1B
antihypertensive agents
TERAZOSIN Antineoplastic Agents; ADRA1D
antihypertensive agents
TERBUTALINE Bronchodilator Agents; Tocolytic ADRB2
Agents
TERFENADINE Anti-Allergic Agents HRH1
TESTOLACTONE Antineoplastic Agents, Hormonal CYP19A1
THIAMYLAL Anesthetics, Intravenous GABRA1
THIAMYLAL Anesthetics, Intravenous KCNJ11
THIAMYLAL Anesthetics, Intravenous KCNJ8
THIETHYLPERAZINE Antiemetics CHRM1
THIETHYLPERAZINE Antiemetics CHRM2
THIETHYLPERAZINE Antiemetics CHRM3
THIETHYLPERAZINE Antiemetics CHRM4
THIETHYLPERAZINE Antiemetics CHRM5
THIETHYLPERAZINE Antiemetics DRD1
THIETHYLPERAZINE Antiemetics DRD2
THIETHYLPERAZINE Antiemetics DRD4
THIETHYLPERAZINE Antiemetics HRH1
THIETHYLPERAZINE Antiemetics HTR2A
THIETHYLPERAZINE Antiemetics HTR2C
THIOPENTAL Anesthetics, Intravenous CHRNA4
THIOPENTAL Anesthetics, Intravenous CHRNA7
THIOPENTAL Anesthetics, Intravenous GABRA1
THIOPENTAL Anesthetics, Intravenous GABRA2
THIOPENTAL Anesthetics, Intravenous GABRA3
THIOPENTAL Anesthetics, Intravenous GABRA4
THIOPENTAL Anesthetics, Intravenous GABRA5
THIOPENTAL Anesthetics, Intravenous GABRA6
THIOPENTAL Anesthetics, Intravenous GRIA2
THIOPENTAL Anesthetics, Intravenous GRIK2
THIORIDAZINE Antipsychotic Agents ADRA1A
THIORIDAZINE Antipsychotic Agents DRD1
THIORIDAZINE Antipsychotic Agents DRD2
THIORIDAZINE Antipsychotic Agents HTR2A
TIAGABINE Anticonvulsants ABAT
TIAGABINE Anticonvulsants SLC6A1
TIAPROFENIC ACID NSAID PTGS2
TICLOPIDINE Platelet Aggregation Inhibitors P2RY12
TILUDRONATE Bisphosphonates PTPN1
TIROFIBAN Platelet Aggregation Inhibitors ITGA2B
TIROFIBAN Platelet Aggregation Inhibitors ITGB3
TOCAINIDE Anti-Arrhythmia Agents SCN5A
TOLAZAMIDE Hypoglycemic Agents KCNJ1
TOLAZOLINE Antihypertensive Agents ADRA1A
TOLBUTAMIDE Hypoglycemic Agents KCNJ1
TOLCAPONE Antiparkinson Agents COMT
TOLMETIN NSAID PTGS1
TOLMETIN NSAID PTGS2
TOPIRAMATE Anticonvulsants; anti-migraine CA2
agents
TOPIRAMATE Anticonvulsants; anti-migraine CA4
agents
TOPIRAMATE Anticonvulsants; anti-migraine GABRA1
agents
TOPIRAMATE Anticonvulsants; anti-migraine GRIK1
agents
TOPIRAMATE Anticonvulsants; anti-migraine SCN1A
agents
TORASEMIDE Antihypertensive Agents; Diuretics SLC12A1
TRANYLCYPROMINE Antidepressive Agents MAOA
TRANYLCYPROMINE Antidepressive Agents MAOB
TREPROSTINIL Antihypertensive Agents; P2RY12
Antithrombotic Agents
TREPROSTINIL Antihypertensive Agents; PPARG
Antithrombotic Agents
TRIAMTERENE Antihypertensive Agents; Diuretics SCNN1A
TRIAMTERENE Antihypertensive Agents; Diuretics SCNN1B
TRIAMTERENE Antihypertensive Agents; Diuretics SCNN1D
TRIAMTERENE Antihypertensive Agents; Diuretics SCNN1G
TRICHLORMETHIAZIDE Antihypertensive Agents; Diuretics CA1
TRICHLORMETHIAZIDE Antihypertensive Agents; Diuretics CA2
TRICHLORMETHIAZIDE Antihypertensive Agents; Diuretics CA4
TRICHLORMETHIAZIDE Antihypertensive Agents; Diuretics KCNMA1
TRICHLORMETHIAZIDE Antihypertensive Agents; Diuretics SLC12A1
TRIDIHEXETHYL GI Anti-Ulcer Agents, CHRM1
anticholinergic; Antispasmodics
TRIDIHEXETHYL GI Anti-Ulcer Agents, CHRM2
anticholinergic; Antispasmodics
TRIDIHEXETHYL GI Anti-Ulcer Agents, CHRM3
anticholinergic; Antispasmodics
TRIFLUOPERAZINE Antiemetics; Antipsychotic Agents ADRA1A
TRIFLUOPERAZINE Antiemetics; Antipsychotic Agents DRD1IP
TRIFLUOPERAZINE Antiemetics; Antipsychotic Agents DRD2
TRIFLUPROMAZINE Antiemetics; Antipsychotic Agents CHRM1
TRIFLUPROMAZINE Antiemetics; Antipsychotic Agents CHRM2
TRIFLUPROMAZINE Antiemetics; Antipsychotic Agents DRD1
TRIFLUPROMAZINE Antiemetics; Antipsychotic Agents DRD2
TRIFLUPROMAZINE Antiemetics; Antipsychotic Agents HTR2B
TRIHEXYPHENIDYL Antiparkinson Agents CHRM1
TRILOSTANE Antiadrenal HSD3B1
TRILOSTANE Antiadrenal HSD3B2
TRIMEPRAZINE Antipruritics HRH1
TRIMETHADIONE Anticonvulsants CACNA1G
TRIMETHAPHAN Antihypertensive Agents; CHRNA10
Vasodilator Agents
TRIMETREXATE Antineoplastic Agents DHFR
TRIMIPRAMINE Antidepressive Agents, Tricyclic SLC6A2
TRIMIPRAMINE Antidepressive Agents, Tricyclic SLC6A4
TRIPELENNAMINE Anti-Allergic Agents HRH1
TRIPROLIDINE Anti-Allergic Agents HRH1
TROPICAMIDE Diagnostic Agents; Mydriatics CHRM4
TUBOCURARINE Muscle Relaxants, Skeletal CHRNA2
VALPROIC ACID Anticonvulsants ABAT
VALRUBICIN Antineoplastic Agents TOP2A
WARFARIN Anticoagulants VKORC1
WARFARIN Anticoagulants VKORC1L1
VINBLASTINE Antineoplastic Agents TUBB2A
VINDESINE Antineoplastic Agents TUBB1
XIMELAGATRAN Anticoagulants F2
YOHIMBINE Mydriatics; Anti-impotence Agents ADRA2A
YOHIMBINE Mydriatics; Anti-impotence Agents ADRA2B
YOHIMBINE Mydriatics; Anti-impotence Agents ADRA2C
ZOPICLONE Hypnotics and Sedatives BZRP
ZOPICLONE Hypnotics and Sedatives GABRA1
ZOPICLONE Hypnotics and Sedatives GABRA2
ZOPICLONE Hypnotics and Sedatives GABRA3
ZOPICLONE Hypnotics and Sedatives GABRA5
ZUCLOPENTHIXOL Antipsychotic Agents DRD1
ZUCLOPENTHIXOL Antipsychotic Agents DRD2
ZUCLOPENTHIXOL Antipsychotic Agents DRD5
5. Uses, Formulation and Administration
Pharmaceutically Acceptable Compositions
According to another embodiment, the invention provides a composition comprising a compound of this invention or a pharmaceutically acceptable derivative thereof and a pharmaceutically acceptable carrier, adjuvant, or vehicle. The amount of compound in compositions of this invention is such that is effective to measurably bind CRBN, or a mutant thereof, and a targeted protein, or a mutant thereof, in a biological sample or in a patient. In certain embodiments, a composition of this invention is formulated for administration to a patient in need of such composition. In some embodiments, a composition of this invention is formulated for oral administration to a patient.
The term “patient,” as used herein, means an animal, preferably a mammal, and most preferably a human.
The term “pharmaceutically acceptable carrier, adjuvant, or vehicle” refers to a non-toxic carrier, adjuvant, or vehicle that does not destroy the pharmacological activity of the compound with which it is formulated. Pharmaceutically acceptable carriers, adjuvants or vehicles that may be used in the compositions of this invention include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium tri silicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol and wool fat.
A “pharmaceutically acceptable derivative” means any non-toxic salt, ester, salt of an ester or other derivative of a compound of this invention that, upon administration to a recipient, is capable of providing, either directly or indirectly, a compound of this invention or an inhibitorily active metabolite or residue thereof.
As used herein, the term “active metabolite or residue thereof” means that a metabolite or residue thereof is also a binder of CRBN, or a mutant thereof, or a targeted protein, or a mutant thereof.
Compositions of the present invention may be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, buccally, vagin*lly or via an implanted reservoir. The term “parenteral” as used herein includes subcutaneous, intravenous, intramuscular, intra-articular, intra-synovial, intrasternal, intrathecal, intrahepatic, intralesional and intracranial injection or infusion techniques. Preferably, the compositions are administered orally, intraperitoneally or intravenously. Sterile injectable forms of the compositions of this invention may be aqueous or oleaginous suspension. These suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium.
For this purpose, any bland fixed oil may be employed including synthetic mono- or di-glycerides. Fatty acids, such as oleic acid and its glyceride derivatives are useful in the preparation of injectables, as are natural pharmaceutically-acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylated versions. These oil solutions or suspensions may also contain a long-chain alcohol diluent or dispersant, such as carboxymethyl cellulose or similar dispersing agents that are commonly used in the formulation of pharmaceutically acceptable dosage forms including emulsions and suspensions. Other commonly used surfactants, such as Tweens, Spans and other emulsifying agents or bioavailability enhancers which are commonly used in the manufacture of pharmaceutically acceptable solid, liquid, or other dosage forms may also be used for the purposes of formulation.
Pharmaceutically acceptable compositions of this invention may be orally administered in any orally acceptable dosage form including, but not limited to, capsules, tablets, aqueous suspensions or solutions. In the case of tablets for oral use, carriers commonly used include lactose and corn starch. Lubricating agents, such as magnesium stearate, are also typically added. For oral administration in a capsule form, useful diluents include lactose and dried cornstarch. When aqueous suspensions are required for oral use, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening, flavoring or coloring agents may also be added.
Alternatively, pharmaceutically acceptable compositions of this invention may be administered in the form of suppositories for rectal administration. These can be prepared by mixing the agent with a suitable non-irritating excipient that is solid at room temperature but liquid at rectal temperature and therefore will melt in the rectum to release the drug. Such materials include cocoa butter, beeswax and polyethylene glycols.
Pharmaceutically acceptable compositions of this invention may also be administered topically, especially when the target of treatment includes areas or organs readily accessible by topical application, including diseases of the eye, the skin, or the lower intestinal tract. Suitable topical formulations are readily prepared for each of these areas or organs.
Topical application for the lower intestinal tract can be effected in a rectal suppository formulation (see above) or in a suitable enema formulation. Topically-transdermal patches may also be used.
For topical applications, provided pharmaceutically acceptable compositions may be formulated in a suitable ointment containing the active component suspended or dissolved in one or more carriers. Carriers for topical administration of compounds of this invention include, but are not limited to, mineral oil, liquid petrolatum, white petrolatum, propylene glycol, polyoxyethylene, polyoxypropylene compound, emulsifying wax and water. Alternatively, provided pharmaceutically acceptable compositions can be formulated in a suitable lotion or cream containing the active components suspended or dissolved in one or more pharmaceutically acceptable carriers. Suitable carriers include, but are not limited to, mineral oil, sorbitan monostearate, polysorbate 60, cetyl esters wax, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol and water.
For ophthalmic use, provided pharmaceutically acceptable compositions may be formulated as micronized suspensions in isotonic, pH adjusted sterile saline, or, preferably, as solutions in isotonic, pH adjusted sterile saline, either with or without a preservative such as benzylalkonium chloride. Alternatively, for ophthalmic uses, the pharmaceutically acceptable compositions may be formulated in an ointment such as petrolatum.
Pharmaceutically acceptable compositions of this invention may also be administered by nasal aerosol or inhalation. Such compositions are prepared according to techniques well-known in the art of pharmaceutical formulation and may be prepared as solutions in saline, employing benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, fluorocarbons, and/or other conventional solubilizing or dispersing agents.
Most preferably, pharmaceutically acceptable compositions of this invention are formulated for oral administration. Such formulations may be administered with or without food. In some embodiments, pharmaceutically acceptable compositions of this invention are administered without food. In other embodiments, pharmaceutically acceptable compositions of this invention are administered with food.
The amount of compounds of the present invention that may be combined with the carrier materials to produce a composition in a single dosage form will vary depending upon the host treated, the particular mode of administration. Preferably, provided compositions should be formulated so that a dosage of between 0.01-100 mg/kg body weight/day of the compound can be administered to a patient receiving these compositions.
It should also be understood that a specific dosage and treatment regimen for any particular patient will depend upon a variety of factors, including the activity of the specific compound employed, the age, body weight, general health, sex, diet, time of administration, rate of excretion, drug combination, and the judgment of the treating physician and the severity of the particular disease being treated. The amount of a compound of the present invention in the composition will also depend upon the particular compound in the composition.
Uses of Compounds and Pharmaceutically Acceptable Compositions
Presently described are compositions and methods that relate to the surprising and unexpected discovery that an E3 Ubiquitin Ligase protein, e.g., cereblon, ubiquitinates a target protein once it and the target protein are placed in proximity by a bifunctional or chimeric construct that binds the E3 Ubiquitin Ligase protein and the target protein. Accordingly the present invention provides such compounds and compositions comprising an E3 Ubiquintin Ligase binding moiety (“UBM”) coupled to a protein target binding moiety (“TBM”), which result in the ubiquitination of a chosen target protein, which leads to degradation of the target protein by the proteasome.
Compounds and compositions described herein are generally useful for the modulation of targeted ubiquitination, especially with respect to a variety of polypeptides and other proteins, which are degraded and/or otherwise inhibited. In some embodiments the protein inhibited by the compounds and methods of the invention comprises those proteins listed herein.
Compounds and compositions described herein exhibit a broad range of pharmacological activities, consistent with the degradation/inhibition of targeted polypeptides.
Accordingly, compounds that bind CRBN are beneficial, especially those with selectivity over E3 ligases. Such compounds should deliver a pharmacological response that favorably treats one or more of the conditions described herein without the side-effects associated with the binding of E3 ligases.
Even though CRBN binders are known in the art, there is a continuing need to provide novel binders having more effective or advantageous pharmaceutically relevant properties. For example, compounds with increased activity, selectivity over other E3 ligases, and ADMET (absorption, distribution, metabolism, excretion, and/or toxicity) properties. Thus, in some embodiments, the present invention provides binders of CRBN which show selectivity over other E3 ligases.
The activity of a compound utilized in this invention as an binder of CRBN, or a mutant thereof, may be assayed in vitro, in vivo or in a cell line. In vitro assays include assays that determine the subsequent functional consequences, or activity of activated CRBN, or a mutant thereof. Alternate in vitro assays quantitate the ability of the compound to bind to CRBN. Binding may be measured by radiolabeling the compound prior to binding, isolating the compound/CRBN complex and determining the amount of radiolabel bound. Alternatively, compound binding may be determined by running a competition experiment where new compounds are incubated with CRBN bound to known radioligands. Representative in vitro and in vivo assays useful in assaying a CRBN binder include those described and disclosed in, Boichenko et al. J. Med. Chem. (2016) 59, 770-774 and Iconomou and Saunders Biochemical Journal (2016) 473, 4083-4101, the entirety of each of which is herein incorporated by reference. Detailed conditions for assaying a compound utilized in this invention as an binder of CRBN, or a mutant thereof, are set forth in the Examples below.
The term“Ubiquitin Ligase” refers to a family of proteins that facilitate the transfer of ubiquitin to a specific substrate protein, targeting the substrate protein for degradation. For example, cereblon is an E3 Ubiquitin Ligase protein that alone or in combination with an E2 ubiquitin-conjugating enzyme causes the attachment of ubiquitin to a lysine on a target protein, and subsequently targets the specific protein substrates for degradation by the proteasome. Thus, E3 ubiquitin ligase alone or in complex with an E2 ubiquitin conjugating enzyme is responsible for the transfer of ubiquitin to targeted proteins. In general, the ubiquitin ligase is involved in polyubiquitination such that a second ubiquitin is attached to the first; a third is attached to the second, and so forth. Polyubiquitination marks proteins for degradation by the proteasome. However, there are some ubiquitination events that are limited to mono-ubiquitination, in which only a single ubiquitin is added by the ubiquitin ligase to a substrate molecule. Mono-ubiquitinated proteins are not targeted to the proteasome for degradation, but may instead be altered in their cellular location or function, for example, via binding other proteins that have domains capable of binding ubiquitin. Further complicating matters, different lysines on ubiquitin can be targeted by an E3 to make chains. The most common lysine is Lys48 on the ubiquitin chain. This is the lysine used to make polyubiquitin, which is recognized by the proteasome.
As used herein, the terms “treatment,” “treat,” and “treating” refer to reversing, alleviating, delaying the onset of, or inhibiting the progress of a disease or disorder, or one or more symptoms thereof, as described herein. In some embodiments, treatment may be administered after one or more symptoms have developed. In other embodiments, treatment may be administered in the absence of symptoms. For example, treatment may be administered to a susceptible individual prior to the onset of symptoms (e.g., in light of a history of symptoms and/or in light of genetic or other susceptibility factors). Treatment may also be continued after symptoms have resolved, for example to prevent or delay their recurrence.
The description provides therapeutic compositions as described herein for effectuating the degradation of proteins of interest for the treatment or amelioration of a disease, e.g., cancer. In certain additional embodiments, the disease is multiple myeloma. As such, in another aspect, the description provides a method of ubiquitinating/degrading a target protein in a cell. In certain embodiments, the method comprises administering a bifunctional compound as described herein comprising, e.g., a UBM and a TBM, linked through a linker moiety, as otherwise described herein, wherein the UBM is coupled to the TBM and wherein the UBM recognizes a ubiquitin pathway protein (e.g., an ubiquitin ligase, preferably an E3 ubiquitin ligase such as, e.g., cereblon) and the TBM recognizes the target protein such that degradation of the target protein will occur when the target protein is placed in proximity to the ubiquitin ligase, thus resulting in degradation/inhibition of the effects of the target protein and the control of protein levels. The control of protein levels afforded by the present invention provides treatment of a disease state or condition, which is modulated through the target protein by lowering the level of that protein in the cell, e.g., cell of a patient. In certain embodiments, the method comprises administering an effective amount of a compound as described herein, optionally including a pharmaceutically acceptable excipient, carrier, adjuvant, another bioactive agent or combination thereof.
In additional embodiments, the description provides methods for treating or emeliorating a disease, disorder or symptom thereof in a subject or a patient, comprising administering to a subject in need thereof a composition comprising an effective amount, e.g., a therapeutically effective amount, of a compound as described herein or salt form thereof, and a pharmaceutically acceptable excipient, carrier, adjuvant, another bioactive agent or combination thereof, wherein the composition is effective for treating or ameliorating the disease or disorder or symptom thereof in the subject.
In another aspect, the description provides methods for identifying the effects of the degradation of proteins of interest in a biological system using compounds according to the present invention.
In another embodiment, the present invention is directed to a method of treating a human patient in need for a disease state or condition modulated through a protein where the degradation of that protein will produce a therapeutic effect in that patient, the method comprising administering to a patient in need an effective amount of a compound according to the present invention, optionally in combination with another bioactive agent. The disease state or condition may be a disease caused by a microbial agent or other exogenous agent such as a virus, bacteria, fungus, protozoa or other microbe or may be a disease state, which is caused by overexpression of a protein, which leads to a disease state and/or condition.
Disease states of conditions which may be treated using compounds according to the present invention include, for example, asthma, autoimmune diseases such as multiple sclerosis, various cancers, ciliopathies, cleft palate, diabetes, heart disease, hypertension, inflammatory bowel disease, mental retardation, mood disorder, obesity, refractive error, infertility, Angelman syndrome, Canavan disease, Coeliac disease, Charcot-Marie-Tooth disease, Cystic fibrosis, duch*enne muscular dystrophy, Haemochromatosis, Haemophilia, Klinefelter's syndrome, Neurofibromatosis, Phenylketonuria, Polycystic kidney disease, (PKD1) or 4 (PKD2) Prader-Willi syndrome, Sickle-cell disease, Tay-Sachs disease, Turner syndrome.
Further disease states or conditions which may be treated by compounds according to the present invention include Alzheimer's disease, Amyotrophic lateral sclerosis (Lou Gehrig's disease), Anorexia nervosa, Anxiety disorder, Atherosclerosis, Attention deficit hyperactivity disorder, Autism, Bipolar disorder, Chronic fatigue syndrome, Chronic obstructive pulmonary disease, Crohn's disease, Coronary heart disease, Dementia, Depression, Diabetes mellitus type 1, Diabetes mellitus type 2, Epilepsy, Guillain-Barré syndrome, Irritable bowel syndrome, Lupus, Metabolic syndrome, Multiple sclerosis, Myocardial infarction, Obesity, Obsessive-compulsive disorder, Panic disorder, Parkinson's disease, Psoriasis, Rheumatoid arthritis, Sarcoidosis, Schizophrenia, Stroke, Thromboangiitis obliterans, Tourette syndrome, Vasculitis.
Still additional disease states or conditions which can be treated by compounds according to the present invention include aceruloplasminemia, Achondrogenesis type II, achondroplasia, Acrocephaly, Gaucher disease type 2, acute intermittent porphyria, Canavan disease, Adenomatous Polyposis Coli, ALA dehydratase deficiency, adenylosuccinate lyase deficiency, Adrenogenital syndrome, Adrenoleukodystrophy, ALA-D porphyria, ALA dehydratase deficiency, Alkaptonuria, Alexander disease, Alkaptonuric ochronosis, alpha 1-antitrypsin deficiency, alpha-1 proteinase inhibitor, emphysema, amyotrophic lateral sclerosis Alstrom syndrome, Alexander disease, Amelogenesis imperfecta, ALA dehydratase deficiency, Anderson-Fabry disease, androgen insensitivity syndrome, Anemia Angiokeratoma Corporis Diffusum, Angiomatosis retinae (von Hippel-Lindau disease) Apert syndrome, Arachnodactyly (Marfan syndrome), Stickler syndrome, Arthrochalasis multiplex congenital (Ehlers-Danlos syndrome #arthrochalasia type) ataxia telangiectasia, Rett syndrome, primary pulmonary hypertension, Sandhoff disease, neurofibromatosis type II, Beare-Stevenson cutis gyrata syndrome, Mediterranean fever, familial, Benjamin syndrome, beta-thalassemia, Bilateral Acoustic Neurofibromatosis (neurofibromatosis type II), factor V Leiden thrombophilia, Bloch-Sulzberger syndrome (incontinentia pigmenti), Bloom syndrome, X-linked sideroblastic anemia, Bonnevie-Ullrich syndrome (Turner syndrome), Bourneville disease (tuberous sclerosis), prion disease, Birt-Hogg-Dubé syndrome, Brittle bone disease (osteogenesis imperfecta), Broad Thumb-Hallux syndrome (Rubinstein-Taybi syndrome), Bronze Diabetes/Bronzed Cirrhosis (hemochromatosis), Bulbospinal muscular atrophy (Kennedy's disease), Burger-Grutz syndrome (lipoprotein lipase deficiency), CGD Chronic granulomatous disorder, Campomelic dysplasia, biotinidase deficiency, Cardiomyopathy (Noonan syndrome), Cri du chat, CAVD (congenital absence of the vas deferens), Caylor cardiofacial syndrome (CBAVD), CEP (congenital erythropoietic porphyria), cystic fibrosis, congenital hypothyroidism, Chondrodystrophy syndrome (achondroplasia), otospondylomegaepiphyseal dysplasia, Lesch-Nyhan syndrome, galactosemia, Ehlers-Danlos syndrome, Thanatophoric dysplasia, Coffin-Lowry syndrome, co*ckayne syndrome, (familial adenomatous polyposis), Congenital erythropoietic porphyria, Congenital heart disease, Methemoglobinemia/Congenital methaemoglobinaemi a, achondroplasia, X-linked sideroblastic anemia, Connective tissue disease, Conotruncal anomaly face syndrome, Cooley's Anemia (beta-thalassemia), Copper storage disease (Wilson's disease), Copper transport disease (Menkes disease), hereditary coproporphyria, Cowden syndrome, Craniofacial dysarthrosis (Crouzon syndrome), Creutzfeldt-Jakob disease (prion disease), co*ckayne syndrome, Cowden syndrome, Curschmann-Batten-Steinert syndrome (myotonic dystrophy), Beare-Stevenson cutis gyrata syndrome, primary hyperoxaluria, spondyloepimetaphyseal dysplasia (Strudwick type), muscular dystrophy, duch*enne and Becker types (DBMD), Usher syndrome, Degenerative nerve diseases including de Grouchy syndrome and Dejerine-Sottas syndrome, developmental disabilities, distal spinal muscular atrophy, type V, androgen insensitivity syndrome, Diffuse Globoid Body Sclerosis (Krabbe disease), Di George's syndrome, Dihydrotestosterone receptor deficiency, androgen insensitivity syndrome, Down syndrome, Dwarfism, erythropoietic protoporphyria Erythroid 5-aminolevulinate synthetase deficiency, Erythropoieti c porphyria, erythropoietic protoporphyria, erythropoietic uroporphyria, Friedreich's ataxia, familial paroxysmal polyserositis, porphyria cutanea tarda, familial pressure sensitive neuropathy, primary pulmonary hypertension (PPH), Fibrocystic disease of the pancreas, fragile X syndrome, galactosemia, genetic brain disorders, Giant cell hepatitis (Neonatal hemochromatosis), Gronblad-Strandberg syndrome (pseudoxanthoma elasticum), Gunther disease (congenital erythropoietic porphyria), haemochromatosis, Hallgren syndrome, sickle cell anemia, hemophilia, hepatoerythropoietic porphyria (HEP), Hippel-Lindau disease (von Hippel-Lindau disease), Huntington's disease, Hutchinson-Gilford progeria syndrome (progeria), Hyperandrogenism, Hypochondroplasia, Hypochromic anemia, Immune system disorders, including X-linked severe combined immunodeficiency, Insley-Astley syndrome, Jackson-Weiss syndrome, Joubert syndrome, Lesch-Nyhan syndrome, Jackson-Weiss syndrome, Kidney diseases, including hyperoxaluria, Klinefelter's syndrome, Kniest dysplasia, Lacunar dementia, Langer-Saldino achondrogenesis, ataxia telangiectasia, Lynch syndrome, Lysyl-hydroxylase deficiency, Machado-Joseph disease, Metabolic disorders, including Kniest dysplasia, Marfan syndrome, Movement disorders, Mowat-Wilson syndrome, cystic fibrosis, Muenke syndrome, Multiple neurofibromatosis, Nance-Insley syndrome, Nance-Sweeney chondrodysplasia, Niemann-Pick disease, Noack syndrome (Pfeiffer syndrome), Osler-Weber-Rendu disease, Peutz-Jeghers syndrome, Polycystic kidney disease, polyostotic fibrous dysplasia (McCune-Albright syndrome), Peutz-Jeghers syndrome, Prader-Labhart-Willi syndrome, hemochromatosis, primary hyperuricemia syndrome (Lesch-Nyhan syndrome), primary pulmonary hypertension, primary senile degenerative dementia, prion disease, progeria (Hutchinson Gilford Progeria Syndrome), progressive chorea, chronic hereditary (Huntington) (Huntington's disease), progressive muscular atrophy, spinal muscular atrophy, propionic acidemia, protoporphyria, proximal myotonic dystrophy, pulmonary arterial hypertension, PXE (pseudoxanthoma elasticum), Rb (retinoblastoma), Recklinghausen disease (neurofibromatosis type I), Recurrent polyserositis, Retinal disorders, Retinoblastoma, Rett syndrome, RFALS type 3, Ricker syndrome, Riley-Day syndrome, Roussy-Levy syndrome, severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), Li-Fraumeni syndrome, sarcoma, breast, leukemia, and adrenal gland (SBLA) syndrome, sclerosis tuberose (tuberous sclerosis), SDAT, SED congenital (spondyloepiphyseal dysplasia congenita), SED Strudwick (spondyloepimetaphyseal dysplasia, Strudwick type), SEDc (spondyloepiphyseal dysplasia congenita) SEMD, Strudwick type (spondyloepimetaphyseal dysplasia, Strudwick type), Shprintzen syndrome, Skin pigmentation disorders, Smith-Lemli-Opitz syndrome, South-African genetic porphyria (variegate porphyria), infantile-onset ascending hereditary spastic paralysis, Speech and communication disorders, sphingolipidosis, Tay-Sachs disease, spinocerebellar ataxia, Stickler syndrome, stroke, androgen insensitivity syndrome, tetrahydrobiopterin deficiency, beta-thalassemia, Thyroid disease, Tomaculous neuropathy (hereditary neuropathy with liability to pressure palsies), Treacher Collins syndrome, Triplo X syndrome (triple X syndrome), Trisomy 21 (Down syndrome), Trisomy X, VHL syndrome (von Hippel-Lindau disease), Vision impairment and blindness (Alström syndrome), Vrolik disease, Waardenburg syndrome, Warburg Sjo Fledelius Syndrome, Weissenbacher-Zweymüller syndrome, Wolf-Hirschhorn syndrome, Wolff Periodic disease, Weissenbacher-Zweymüller syndrome and Xeroderma pigmentosum, among others.
The term “neoplasia” or“cancer” is used throughout the specification to refer to the pathological process that results in the formation and growth of a cancerous or malignant neoplasm, i.e., abnormal tissue that grows by cellular proliferation, often more rapidly than normal and continues to grow after the stimuli that initiated the new growth cease. Malignant neoplasms show partial or complete lack of structural organization and functional coordination with the normal tissue and most invade surrounding tissues, metastasize to several sites, and are likely to recur after attempted removal and to cause the death of the patient unless adequately treated. As used herein, the term neoplasia is used to describe all cancerous disease states and embraces or encompasses the pathological process associated with malignant hematogenous, ascitic and solid tumors. Exemplary cancers which may be treated by the present compounds either alone or in combination with at least one additional anti-cancer agent include squamous-cell carcinoma, basal cell carcinoma, adenocarcinoma, hepatocellular carcinomas, and renal cell carcinomas, cancer of the bladder, bowel, breast, cervix, colon, esophagus, head, kidney, liver, lung, neck, ovary, pancreas, prostate, and stomach; leukemias; benign and malignant lymphomas, particularly Burkitt's lymphoma and Non-Hodgkin's lymphoma; benign and malignant melanomas; myeloproliferative diseases; sarcomas, including Ewing's sarcoma, hemangiosarcoma, Kaposi's sarcoma, liposarcoma, myosarcomas, peripheral neuroepithelioma, synovial sarcoma, gliomas, astrocytomas, oligodendrogliomas, ependymomas, gliobastomas, neuroblastomas, ganglioneuromas, gangliogliomas, medulloblastomas, pineal cell tumors, meningiomas, meningeal sarcomas, neurofibromas, and Schwannomas; bowel cancer, breast cancer, prostate cancer, cervical cancer, uterine cancer, lung cancer, ovarian cancer, testicular cancer, thyroid cancer, astrocytoma, esophageal cancer, pancreatic cancer, stomach cancer, liver cancer, colon cancer, melanoma; carcinosarcoma, Hodgkin's disease, Wilms' tumor and teratocarcinomas. Additional cancers which may be treated using compounds according to the present invention include, for example, T-lineage Acute lymphoblastic Leukemia (T-ALL), T-lineage lymphoblastic Lymphoma (T-LL), Peripheral T-cell lymphoma, Adult T-cell Leukemia, Pre-B ALL, Pre-B Lymphomas, Large B-cell Lymphoma, Burkitts Lymphoma, B-cell ALL, Philadelphia chromosome positive ALL and Philadelphia chromosome positive CML.
In some embodiments, the present invention provides a method for treating one or more disorders, wherein the disorders are selected from autoimmune disorders, inflammatory disorders, proliferative disorders, endocrine disorders, neurological disorders, and disorders associated with transplantation, said method comprising administering to a patient in need thereof, a pharmaceutical composition comprising an effective amount of a compound of the present invention, or a pharmaceutically acceptable salt thereof.
In some embodiments, compounds of the present invention induce the ubiquitination and degradation of a target protein selected from the group consisting of
A1BG, A1CF, A2M,
A2ML1, A3GALT2, A4GALT, A4GNT, AAAS, AACS, AADAC, AADACL2, AADACL3,
AADACL4, AADAT, AAED1, AAGAB, AAK1, AAMDC, AAMP, AANAT, AAR2, AARD,
AARS, AARS2, AARSD1, AASDH, AASDHPPT, AASS, AATF, AATK, AATK-AS1, ABAT,
ABCA1, ABCA10, ABCA12, ABCA13, ABCA2, ABCA3, ABCA4, ABCA5, ABCA6, ABCA7,
ABCA8, ABCA9, ABCB1, ABCB10, ABCB11, ABCB4, ABCB5, ABCB6, ABCB7, ABCB8,
ABCB9, ABCC1, ABCC10, ABCC11, ABCC12, ABCC2, ABCC3, ABCC4, ABCC5, ABCC6,
ABCC8, ABCC9, ABCD1, ABCD2, ABCD3, ABCD4, ABCE1, ABCF1, ABCF2, ABCF3,
ABCG1, ABCG2, ABCG4, ABCG5, ABCG8, ABHD1, ABHD10, ABHD11, ABHD12,
ABHD12B, ABHD13, ABHD14A, ABHD14A-ACY1, ABHD14B, ABHD15, ABHD16A,
ABHD16B, ABHD17A, ABHD17B, ABHD17C, ABHD18, ABHD2, ABHD3, ABHD4, ABHD5,
ABHD6, ABHD8, ABI1, ABI2, ABI3, ABI3BP, ABL1, ABL2, ABLIM1, ABLIM2, ABLIM3,
ABO, ABR, ABRA, ABRACL, ABRAXAS1, ABRAXAS2, ABT1, ABTB1, ABTB2,
AC001226.2, AC002094.3, AC002115.2, AC002310.4, AC002310.5, AC002429.2, AC002985.1,
AC002996.1, AC003002.1, AC003002.2, AC003002.3, AC003002.4, AC003005.1, AC003006.1,
AC003688.1, AC004076.1, AC004080.3, AC004223.3, AC004233.2, AC004556.1, AC004691.2,
AC004706.4, AC004754.1, AC004805.1, AC004832.3, AC004922.1, AC004997.1, AC005020.2,
AC005041.1, AC005154.6, AC005258.1, AC005324.3, AC005324.4, AC005520.1, AC005551.1,
AC005670.2, AC005697.1, AC005702.2, AC005726.2, AC005779.2, AC005832.4, AC005833.1,
AC005833.3, AC005837.2, AC005841.2, AC005885.1, AC005943.1, AC006030.1, AC006254.1,
AC006269.1, AC006449.4, AC006486.1, AC006538.2, AC006978.2, AC007040.2, AC007192.1,
AC007240.1, AC007325.1, AC007325.2, AC007325.4, AC007326.4, AC007375.2, AC007383.6,
AC007537.5, AC007731.5, AC007906.2, AC007998.2, AC008073.3, AC008162.2, AC008393.2,
AC008403.1, AC008481.3, AC008537.1, AC008560.1, AC008575.1, AC008575.2, AC008687.1,
AC008687.4, AC008687.8, AC008695.1, AC008735.6, AC008750.8, AC008758.1, AC008758.4,
AC008758.5, AC008758.6, AC008763.2, AC008763.3, AC008764.1, AC008764.4, AC008770.2,
AC008770.3, AC008878.1, AC008878.2, AC008878.3, AC008982.1, AC008982.3, AC009014.1,
AC009086.2, AC009119.2, AC009122.1, AC009133.6, AC009163.2, AC009163.4, AC009286.3,
AC009336.2, AC009477.2, AC009690.1, AC009690.3, AC009779.3, AC010132.3, AC010255.3,
AC010319.2, AC010323.1, AC010325.1, AC010326.2, AC010327.1, AC010422.3, AC010422.5,
AC010422.6, AC010463.1, AC010487.3, AC010522.1, AC010531.1, AC010542.3, AC010547.4,
AC010547.5, AC010615.4, AC010616.1, AC010619.1, AC010646.1, AC010724.2, AC011005.1,
AC011043.1, AC011043.2, AC011195.2, AC011295.1, AC011346.1, AC011448.1, AC011452.1,
AC011455.3, AC011455.4, AC011462.1, AC011473.4, AC011479.1, AC011498.4, AC011499.1,
AC011511.1, AC011511.4, AC011530.1, AC011604.2, AC011841.1, AC012184.2, AC012254.2,
AC012309.1, AC012314.1, AC012314.10, AC012314.11, AC012314.12, AC012314.4,
AC012314.5, AC012314.6, AC012314.8, AC012531.3, AC012651.1, AC013269.1, AC013271.1,
AC013394.1, AC013470.2, AC015688.5, AC015802.6, AC015813.2, AC017081.3, AC017081.4,
AC017081.5, AC017083.4, AC018512.1, AC018523.2, AC018554.3, AC018630.6, AC018709.1,
AC018755.2, AC018793.1, AC018793.2, AC018793.3, AC018793.4, AC018793.5, AC019117.3,
AC020636.2, AC020909.1, AC020914.1, AC020915.1, AC020915.2, AC020915.6, AC020922.1,
AC020934.3, AC021072.1, AC022016.2, AC022167.5, AC022335.1, AC022384.1, AC022400.6,
AC022826.2, AC023055.1, AC023491.2, AC023509.3, AC024592.3, AC024940.1, AC024940.6,
AC025165.3, AC025263.2, AC025283.2, AC025287.4, AC025594.2, AC026369.8, AC026398.1,
AC026461.4, AC026464.1, AC026464.3, AC026464.4, AC026786.1, AC026954.2, AC027796.3,
AC034102.2, AC036214.3, AC037459.1, AC037482.2, AC037482.3, AC040162.1, AC040162.4,
AC044810.8, AC046185.1, AC048338.1, AC051649.2, AC053481.5, AC055811.2, AC058822.1,
AC064853.2, AC064853.3, AC064853.4, AC064853.5, AC064853.6, AC067968.1, AC068234.1,
AC068533.4, AC068547.1, AC068580.4, AC068631.2, AC068775.1, AC068775.2, AC068790.8,
AC068896.1, AC068946.1, AC068987.5, AC069257.3, AC069368.1, AC069503.2, AC069544.2,
AC072022.1, AC073082.1, AC073111.3, AC073111.5, AC073264.3, AC073508.2, AC073610.2,
AC073610.3, AC073612.1, AC073896.1, AC074143.1, AC078927.1, AC079325.2, AC079447.1,
AC079594.2, AC083800.1, AC083902.2, AC084337.2, AC087289.3, AC087498.1, AC087632.1,
AC090004.1, AC090227.1, AC090360.1, AC090527.2, AC090958.3, AC091167.3, AC091167.7,
AC091167.8, AC091304.7, AC091491.1, AC091551.1, AC091959.3, AC091980.2, AC092017.3,
AC092042.3, AC092073.1, AC092111.3, AC092143.1, AC092329.3, AC092442.1, AC092587.1,
AC092647.5, AC092718.3, AC092718.8, AC092821.1, AC092824.3, AC092835.1, AC093155.3,
AC093227.3, AC093423.3, AC093525.1, AC093525.2, AC093668.1, AC093762.1, AC093762.2,
AC093762.3, AC093899.2, AC096582.3, AC096887.1, AC097372.1, AC097495.1, AC097637.1,
AC097662.2, AC098484.3, AC098650.1, AC098850.4, AC099329.3, AC099489.1, AC099518.3,
AC099811.2, AC099850.2, AC100868.1, AC104109.3, AC104151.1, AC104304.1, AC104452.1,
AC104532.1, AC104534.3, AC104581.1, AC104581.3, AC104662.2, AC104836.1, AC105001.2,
AC105052.1, AC106774.10, AC106774.5, AC106774.6, AC106774.7, AC106774.8,
AC106774.9, AC106782.1, AC106886.5, AC107871.1, AC108488.2, AC108750.1, AC108941.2,
AC109583.3, AC110275.1, AC112229.3, AC112484.1, AC113189.6, AC113189.9, AC113331.2,
AC113554.2, AC114296.1, AC114490.2, AC115220.1, AC116366.3, AC116565.1, AC117457.1,
AC118470.1, AC118553.2, AC119396.1, AC119674.2, AC120057.3, AC120114.5, AC124312.1,
AC126755.2, AC127537.5, AC127537.6, AC127537.8, AC129492.3, AC131097.2, AC131160.1,
AC133551.1, AC133555.3, AC134669.2, AC134772.2, AC135050.2, AC135068.1, AC135068.2,
AC135068.3, AC135068.8, AC135178.2, AC135586.2, AC136352.3, AC136352.4, AC136428.1,
AC136612.1, AC136616.1, AC136616.2, AC136616.3, AC137834.1, AC138517.2, AC138647.1,
AC138696.1, AC138811.2, AC138894.1, AC138969.1, AC139530.2, AC139677.1, AC139677.2,
AC140504.1, AC141272.1, AC142391.1, AC142525.4, AC145029.2, AC145212.1, AC145212.2,
AC171558.1, AC171558.3, AC171558.5, AC171558.6, AC187653.1, AC207056.1, AC209232.1,
AC209539.2, AC210544.1, AC213203.1, AC229888.1, AC229888.10, AC229888.2,
AC229888.3, AC229888.4, AC229888.5, AC229888.6, AC229888.7, AC229888.8, AC229888.9,
AC233282.1, AC233282.2, AC233723.1, AC233724.12, AC233724.16, AC233724.17,
AC233724.18, AC233724.19, AC233724.20, AC233724.21, AC233724.6, AC233755.1,
AC233755.2, AC233992.2, AC234301.1, AC234301.3, AC234635.1, AC234635.3, AC234635.4,
AC234635.5, AC236040.1, AC239612.1, AC239618.1, AC239618.2, AC239618.3, AC239618.4,
AC239618.5, AC239618.6, AC239618.7, AC239618.9, AC239799.1, AC240274.1, AC241401.1,
AC241409.2, AC241410.1, AC241556.3, AC241556.4, AC241640.1, AC241640.2, AC241640.4,
AC242528.1, AC242528.2, AC243547.3, AC243733.1, AC243734.1, AC243756.1, AC243790.1,
AC243967.1, AC244196.1, AC244196.2, AC244196.3, AC244196.4, AC244196.5, AC244197.3,
AC244216.4, AC244216.5, AC244226.1, AC244226.2, AC244472.1, AC244472.2, AC244472.3,
AC244472.4, AC244472.5, AC244489.1, AC244489.2, AC244517.10, AC244517.6,
AC245033.1, AC245034.2, AC245078.1, AC245088.2, AC245088.3, AC245369.1, AC245369.2,
AC245369.3, AC245369.4, AC245369.6, AC245427.1, AC245427.3, AC245427.4, AC245427.5,
AC245427.6, AC245427.7, AC245427.8, AC245427.9, AC245748.1, AC247036.3, AC247036.4,
AC247036.5, AC247036.6, AC254560.1, AC254788.1, AC254788.2, AC254952.1, AC255093.3,
AC255093.5, AC256236.1, AC256236.2, AC256236.3, AC256300.2, AC256309.2, AC270107.1,
AC270107.10, AC270107.12, AC270107.2, AC270107.3, AC270107.4, AC270107.5,
AC270107.7, AC270107.8, AC270107.9, AC270227.1, AC270306.4, AC275455.2, ACAA1,
ACAA2, ACACA, ACACB, ACAD10, ACAD11, ACAD8, ACAD9, ACADL, ACADM,
ACADS, ACADSB, ACADVL, ACAN, ACAP1, ACAP2, ACAP3, ACAT1, ACAT2, ACBD3,
ACBD4, ACBD5, ACBD6, ACBD7, ACCS, ACCSL, ACD, ACE, ACE2, ACER1, ACER2,
ACER3, ACHE, ACIN1, ACKR1, ACKR2, ACKR3, ACKR4, ACLY, ACMSD, ACO1, ACO2,
ACOD1, ACOT1, ACOT11, ACOT12, ACOT13, ACOT2, ACOT4, ACOT6, ACOT7, ACOT8,
ACOT9, ACOX1, ACOX2, ACOX3, ACOXL, ACP1, ACP2, ACP4, ACP5, ACP6, ACP7, ACPP,
ACR, ACRBP, ACRV1, ACSBG1, ACSBG2, ACSF2, ACSF3, ACSL1, ACSL3, ACSL4,
ACSL5, ACSL6, ACSM1, ACSM2A, ACSM2B, ACSM3, ACSM4, ACSM5, ACSM6, ACSS1,
ACSS2, ACSS3, ACTA1, ACTA2, ACTB, ACTBL2, ACTC1, ACTG1, ACTG2, ACTL10,
ACTL6A, ACTL6B, ACTL7A, ACTL7B, ACTL8, ACTL9, ACTN1, ACTN2, ACTN3, ACTN4,
ACTR10, ACTRIA, ACTRIB, ACTR2, ACTR3, ACTR3B, ACTR3C, ACTR5, ACTR6,
ACTR8, ACTRT1, ACTRT2, ACTRT3, ACVR1, ACVRIB, ACVRIC, ACVR2A, ACVR2B,
ACVRL1, ACY1, ACY3, ACYP1, ACYP2, AD000671.1, AD000671.2, ADA, ADA2, ADAD1,
ADAD2, ADAL, ADAM10, ADAM11, ADAM12, ADAM15, ADAM17, ADAM18, ADAM19,
ADAM2, ADAM20, ADAM21, ADAM22, ADAM23, ADAM28, ADAM29, ADAM30,
ADAM32, ADAM33, ADAM7, ADAM8, ADAM9, ADAMDEC1, ADAMTS1, ADAMTS10,
ADAMTS12, ADAMTS13, ADAMTS14, ADAMTS15, ADAMTS16, ADAMTS17,
ADAMTS18, ADAMTS19, ADAMTS2, ADAMTS20, ADAMTS3, ADAMTS4, ADAMTS5,
ADAMTS6, ADAMTS7, ADAMTS8, ADAMTS9, ADAMTSL1, ADAMTSL2, ADAMTSL3,
ADAMTSL4, ADAMTSL5, ADAP1, ADAP2, ADAR, ADARB1, ADARB2, ADAT1, ADAT2,
ADAT3, ADCK1, ADCK2, ADCK5, ADCY1, ADCY10, ADCY2, ADCY3, ADCY4, ADCY5,
ADCY6, ADCY7, ADCY8, ADCY9, ADCYAP1, ADCYAPIR1, ADD1, ADD2, ADD3, ADGB,
ADGRA1, ADGRA2, ADGRA3, ADGRB1, ADGRB2, ADGRB3, ADGRD1, ADGRD2,
ADGRE1, ADGRE2, ADGRE3, ADGRE5, ADGRF1, ADGRF2, ADGRF3, ADGRF4, ADGRF5,
ADGRG1, ADGRG2, ADGRG3, ADGRG4, ADGRG5, ADGRG6, ADGRG7, ADGRL1,
ADGRL2, ADGRL3, ADGRL4, ADGRV1, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6,
ADH7, ADHFE1, ADI1, ADIG, ADIPOQ, ADIPOR1, ADIPOR2, ADIRF, ADK, ADM, ADM2,
ADM5, ADNP, ADNP2, ADO, ADORA1, ADORA2A, ADORA2B, ADORA3, ADPGK,
ADPRH, ADPRHL1, ADPRHL2, ADPRM, ADRA1A, ADRA1B, ADRA1D, ADRA2A,
ADRA2B, ADRA2C, ADRB1, ADRB2, ADRB3, ADRM1, ADSL, ADSS, ADSSL1, ADTRP,
AEBP1, AEBP2, AEN, AES, AF130351.1, AF241726.2, AFAP1, AFAPIL1, AFAPIL2, AFDN,
AFF1, AFF2, AFF3, AFF4, AFGIL, AFG3L2, AFM, AFMID, AFP, AFTPH, AGA, AGAP1,
AGAP2, AGAP3, AGAP4, AGAP5, AGAP6, AGAP9, AGBL1, AGBL2, AGBL3, AGBL4,
AGBL5, AGER, AGFG1, AGFG2, AGGF1, AGK, AGL, AGMAT, AGMO, AGO1, AGO2,
AGO3, AGO4, AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPAT5, AGPS, AGR2, AGR3,
AGRN, AGRP, AGT, AGTPBP1, AGTR1, AGTR2, AGTRAP, AGXT, AGXT2, AHCTF1,
AHCY, AHCYL1, AHCYL2, AHDC1, AHI1, AHNAK, AHNAK2, AHR, AHRR, AHSA1,
AHSA2, AHSG, AHSP, AICDA, AIDA, AIF1, AIFIL, AIFM1, AIFM2, AIFM3, AIG1, AIM2,
AIMP1, AIMP2, AIP, AIPL1, AIRE, AJAP1, AJUBA, AK1, AK2, AK3, AK4, AK5, AK6, AK7,
AK8, AK9, AKAIN1, AKAP1, AKAP10, AKAP11, AKAP12, AKAP13, AKAP14, AKAP17A,
AKAP2, AKAP3, AKAP4, AKAP5, AKAP6, AKAP7, AKAP8, AKAP8L, AKAP9, AKIP1,
AKIRIN1, AKIRIN2, AKNA, AKNAD1, AKR1A1, AKRIB1, AKRIB10, AKRIB15, AKRIC1,
AKRIC2, AKRIC3, AKRIC4, AKRID1, AKRIE2, AKR7A2, AKR7A3, AKR7L, AKT1,
AKTIS1, AKT2, AKT3, AKTIP, AL020996.2, AL021154.3, AL021546.1, AL021997.3,
AL022238.4, AL022318.4, AL024498.2, AL031708.1, AL032819.3, AL033529.1, AL035425.2,
AL035460.1, AL049634.2, AL049650.1, AL049697.1, AL049779.1, AL049839.2, AL049844.1,
AL049844.3, AL080251.1, AL096814.1, AL096870.1, AL109810.2, AL109811.4, AL109827.1,
AL109936.3, AL109936.4, AL110118.2, AL110118.4, AL117258.1, AL117339.5, AL117348.2,
AL121581.1, AL121594.3, AL121722.1, AL121753.1, AL121758.1, AL121845.2, AL121845.3,
AL132671.2, AL132780.3, AL133352.1, AL133414.1, AL133414.2, AL136295.1, AL136295.3,
AL136295.4, AL136295.5, AL136373.1, AL136531.2, AL138694.1, AL138752.2, AL138826.1,
AL139011.2, AL139260.3, AL139300.1, AL139353.1, AL157392.5, AL159163.1, AL160275.1,
AL160276.1, AL160396.2, AL161669.4, AL161911.1, AL162231.1, AL162231.3, AL163195.3,
AL163636.2, AL353572.3, AL353588.1, AL354761.2, AL354822.1, AL355102.2, AL355315.1,
AL355860.1, AL355916.3, AL355987.1, AL355987.3, AL356585.9, AL357673.1, AL358075.4,
AL359736.1, AL359736.3, AL359922.1, AL360181.3, AL360181.5, AL365205.1, AL365214.3,
AL365232.1, AL365273.2, AL391650.1, AL449266.1, AL451007.3, AL512428.1, AL512506.3,
AL512785.2, AL513165.2, AL513523.10, AL513523.9, AL583836.1, AL589666.1, AL590132.1,
AL590560.1, AL591806.3, AL592183.1, AL592490.1, AL593848.2, AL603832.3, AL645922.1,
AL645941.2, AL662828.1, AL662852.6, AL662899.1, AL662899.2, AL662899.3, AL669918.1,
AL672043.1, AL672142.1, AL691442.1, AL713999.1, AL772284.2, AL807752.6, AL807752.7,
AL844853.2, AL845331.2, AL845464.1, AL928654.4, AL929554.1, AL929561.7, ALAD,
ALAS1, ALAS2, ALB, ALCAM, ALDH16A1, ALDH18A1, ALDH1A1, ALDH1A2,
ALDH1A3, ALDH1B1, ALDH1L1, ALDH1L2, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1,
ALDH3B2, ALDH4A1, ALDH5A1, ALDH6A1, ALDH7A1, ALDH8A1, ALDH9A1, ALDOA,
ALDOB, ALDOC, ALG1, ALG10, ALG10B, ALG11, ALG12, ALG13, ALG14, ALGIL,
ALG1L2, ALG2, ALG3, ALG5, ALG6, ALG8, ALG9, ALK, ALKAL1, ALKAL2, ALKBH1,
ALKBH2, ALKBH3, ALKBH4, ALKBH5, ALKBH6, ALKBH7, ALKBH8, ALLC, ALMS1,
ALOX12, ALOX12B, ALOX15, ALOX15B, ALOX5, ALOX5AP, ALOXE3, ALPI, ALPK1,
ALPK2, ALPK3, ALPL, ALPP, ALPPL2, ALS2, ALS2CL, ALS2CR12, ALX1, ALX3, ALX4,
ALYREF, AMACR, AMBN, AMBP, AMBRA1, AMD1, AMDHD1, AMDHD2, AMELX,
AMELY, AMER1, AMER2, AMER3, AMFR, AMH, AMHR2, AMIGO1, AMIGO2, AMIGO3,
AMMECR1, AMMECRIL, AMN, AMN1, AMOT, AMOTL1, AMOTL2, AMPD1, AMPD2,
AMPD3, AMPH, AMT, AMTN, AMY1A, AMY1B, AMY1C, AMY2A, AMY2B, AMZ1,
AMZ2, ANAPC1, ANAPC10, ANAPC11, ANAPC13, ANAPC15, ANAPC16, ANAPC2,
ANAPC4, ANAPC5, ANAPC7, ANG, ANGEL1, ANGEL2, ANGPT1, ANGPT2, ANGPT4,
ANGPTL1, ANGPTL2, ANGPTL3, ANGPTL4, ANGPTL5, ANGPTL6, ANGPTL7, ANGPTL8,
ANHX, ANK1, ANK2, ANK3, ANKAR, ANKDDIA, ANKDD1B, ANKEF1, ANKFN1,
ANKFY1, ANKH, ANKHD1, ANKHD1-EIF4EBP3, ANKIB1, ANKK1, ANKLE1, ANKLE2,
ANKMY1, ANKMY2, ANKRA2, ANKRD1, ANKRD10, ANKRD11, ANKRD12, ANKRD13A,
ANKRD13B, ANKRD13C, ANKRD13D, ANKRD16, ANKRD17, ANKRD18A, ANKRD18B,
ANKRD2, ANKRD20A1, ANKRD20A2, ANKRD20A3, ANKRD20A4, ANKRD20A8P,
ANKRD22, ANKRD23, ANKRD24, ANKRD26, ANKRD27, ANKRD28, ANKRD29,
ANKRD30A, ANKRD30B, ANKRD30BL, ANKRD31, ANKRD33, ANKRD33B, ANKRD34A,
ANKRD34B, ANKRD34C, ANKRD35, ANKRD36, ANKRD36B, ANKRD36C, ANKRD37,
ANKRD39, ANKRD40, ANKRD42, ANKRD44, ANKRD45, ANKRD46, ANKRD49,
ANKRD50, ANKRD52, ANKRD53, ANKRD54, ANKRD55, ANKRD6, ANKRD60,
ANKRD61, ANKRD62, ANKRD63, ANKRD65, ANKRD66, ANKRD7, ANKRD9, ANKSIA,
ANKS1B, ANKS3, ANKS4B, ANKS6, ANKUB1, ANKZF1, ANLN, ANO1, ANO10, ANO2,
ANO3, ANO4, ANO5, ANO6, ANO7, ANO8, ANO9, ANOS1, ANP32A, ANP32B, ANP32D,
ANP32E, ANPEP, ANTXR1, ANTXR2, ANTXRL, ANXA1, ANXA10, ANXA11, ANXA13,
ANXA2, ANXA2R, ANXA3, ANXA4, ANXA5, ANXA6, ANXA7, ANXA8, ANXA8L1,
ANXA9, AOAH, AOC1, AOC2, AOC3, AOX1, AP000275.2, AP000295.1, AP000311.1,
AP000322.1, AP000349.1, AP000350.12, AP000350.4, AP000351.3, AP000351.7, AP000721.1,
AP000781.2, AP001160.5, AP001273.2, AP001458.2, AP001781.3, AP001931.1, AP002360.1,
AP002373.1, AP002495.1, AP002512.3, AP002512.4, AP002748.4, AP002990.1, AP003071.5,
AP003108.2, AP003419.2, AP004243.1, AP006285.3, APIAR, AP1B1, APIG1, AP1G2,
APIM1, AP1M2, AP1S1, AP1S2, AP1S3, AP2A1, AP2A2, AP2B1, AP2M1, AP2S1, AP3B1,
AP3B2, AP3D1, AP3M1, AP3M2, AP3S1, AP3S2, AP4B1, AP4E1, AP4M1, AP4S1, AP5B1,
AP5M1, AP5S1, AP5Z1, APAF1, APBA1, APBA2, APBA3, APBB1, APBBIIP, APBB2,
APBB3, APC, APC2, APCDD1, APCDDIL, APCS, APEH, APELA, APEX1, APEX2, APHIA,
APH1B, API5, APIP, APLF, APLN, APLNR, APLP1, APLP2, APMAP, APOA1, APOA2,
APOA4, APOA5, APOB, APOBEC1, APOBEC2, APOBEC3A, APOBEC3B, APOBEC3C,
APOBEC3D, APOBEC3F, APOBEC3G, APOBEC3H, APOBEC4, APOBR, APOC1, APOC2,
APOC3, APOC4, APOC4-APOC2, APOD, APOE, APOF, APOH, APOL1, APOL2, APOL3,
APOL4, APOL5, APOL6, APOLD1, APOM, APOO, APOOL, APOPT1, APP, APPBP2, APPL1,
APPL2, APRT, APTX, AQP1, AQP10, AQP11, AQP12A, AQP12B, AQP2, AQP3, AQP4,
AQP5, AQP6, AQP7, AQP8, AQP9, AQR, AR, ARAF, ARAP1, ARAP2, ARAP3, ARC,
ARCN1, AREG, AREL1, ARF1, ARF3, ARF4, ARF5, ARF6, ARFGAP1, ARFGAP2,
ARFGAP3, ARFGEF1, ARFGEF2, ARFGEF3, ARFIP1, ARFIP2, ARFRP1, ARG1, ARG2,
ARGFX, ARGLU1, ARHGAP1, ARHGAP10, ARHGAP11A, ARHGAP11B, ARHGAP12,
ARHGAP15, ARHGAP17, ARHGAP18, ARHGAP19, ARHGAP19-SLIT1, ARHGAP20,
ARHGAP21, ARHGAP22, ARHGAP23, ARHGAP24, ARHGAP25, ARHGAP26, ARHGAP27,
ARHGAP28, ARHGAP29, ARHGAP30, ARHGAP31, ARHGAP32, ARHGAP33, ARHGAP35,
ARHGAP36, ARHGAP39, ARHGAP4, ARHGAP40, ARHGAP42, ARHGAP44, ARHGAP45,
ARHGAP5, ARHGAP6, ARHGAP8, ARHGAP9, ARHGDIA, ARHGDIB, ARHGDIG,
ARHGEF1, ARHGEF10, ARHGEF10L, ARHGEF11, ARHGEF12, ARHGEF15, ARHGEF16,
ARHGEF17, ARHGEF18, ARHGEF19, ARHGEF2, ARHGEF25, ARHGEF26, ARHGEF28,
ARHGEF3, ARHGEF33, ARHGEF35, ARHGEF37, ARHGEF38, ARHGEF39, ARHGEF4,
ARHGEF40, ARHGEF5, ARHGEF6, ARHGEF7, ARHGEF9, ARIDIA, ARIDIB, ARID2,
ARID3A, ARID3B, ARID3C, ARID4A, ARID4B, ARIDSA, ARID5B, ARIH1, ARIH2,
ARIH2OS, ARL1, ARL10, ARL11, ARL13A, ARL13B, ARL14, ARL14EP, ARL14EPL,
ARL15, ARL16, ARL17A, ARL17B, ARL2, ARL2BP, ARL2-SNX15, ARL3, ARL4A, ARL4C,
ARL4D, ARL5A, ARL5B, ARL5C, ARL6, ARL6IP1, ARL6IP4, ARL6IP5, ARL6IP6, ARL8A,
ARL8B, ARL9, ARMC1, ARMC10, ARMC12, ARMC2, ARMC3, ARMC4, ARMC5, ARMC6,
ARMC7, ARMC8, ARMC9, ARMCX1, ARMCX2, ARMCX3, ARMCX4, ARMCX5
ARMCX6, ARMS2, ARMT1, ARNT, ARNT2, ARNTL, ARNTL2, ARPCIA, ARPC1B, ARPC2,
ARPC3, ARPC4, ARPC4-TTLL3, ARPC5, ARPC5L, ARPIN, ARPP19, ARPP21, ARR3,
ARRB1, ARRB2, ARRDC1, ARRDC2, ARRDC3, ARRDC4, ARRDC5, ARSA, ARSB, ARSD,
ARSE, ARSF, ARSG, ARSH, ARSI, ARSJ, ARSK, ART1, ART3, ART4, ART5, ARTN, ARV1,
ARVCF, ARX, AS3MT, ASAH1, ASAH2, ASAH2B, ASAP1, ASAP2, ASAP3, ASB1, ASB10,
ASB11, ASB12, ASB13, ASB14, ASB15, ASB16, ASB17, ASB18, ASB2, ASB3, ASB4, ASB5,
ASB6, ASB7, ASB8, ASB9, ASCC1, ASCC2, ASCC3, ASCL1, ASCL2, ASCL3, ASCL4,
ASCL5, ASFIA, ASFIB, ASGR1, ASGR2, ASH1L, ASH2L, ASIC1, ASIC2, ASIC3, ASIC4,
ASIC5, ASIP, ASL, ASMT, ASMTL, ASNA1, ASNS, ASNSD1, ASPA, ASPDH, ASPG, ASPH,
ASPHD1, ASPHD2, ASPM, ASPN, ASPRV1, ASPSCR1, ASRGL1, ASS1, ASTE1, ASTL,
ASTN1, ASTN2, ASXL1, ASXL2, ASXL3, ASZ1, ATAD1, ATAD2, ATAD2B, ATAD3A,
ATAD3B, ATAD3C, ATAD5, ATAT1, ATCAY, ATE1, ATF1, ATF2, ATF3, ATF4, ATF5,
ATF6, ATF6B, ATF7, ATF7IP, ATF7IP2, ATG10, ATG101, ATG12, ATG13, ATG14,
ATG16L1, ATG16L2, ATG2A, ATG2B, ATG3, ATG4A, ATG4B, ATG4C, ATG4D, ATG5,
ATG7, ATG9A, ATG9B, ATIC, ATL1, ATL2, ATL3, ATM, ATMIN, ATN1, ATOH1, ATOH7,
ATOH8, ATOX1, ATP10A, ATP10B, ATP1OD, ATP11A, ATP11B, ATP11C, ATP12A,
ATP13A1, ATP13A2, ATP13A3, ATP13A4, ATP13A5, ATP1A1, ATP1A2, ATP1A3, ATP1A4,
ATP1B1, ATP1B2, ATP1B3, ATP1B4, ATP23, ATP2A1, ATP2A2, ATP2A3, ATP2B1,
ATP2B2, ATP2B3, ATP2B4, ATP2C1, ATP2C2, ATP4A, ATP4B, ATP5A1, ATP5B, ATP5C1,
ATP5D, ATP5E, ATPSEP2, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5H, ATP51, ATP5J,
ATP5J2, ATP5J2-PTCD1, ATP5L, ATP5L2, ATP50, ATP5S, ATP6AP1, ATP6AP1L,
ATP6AP2, ATP6VOA1, ATP6VOA2, ATP6VOA4, ATP6VOB, ATP6VOC, ATP6VOD1,
ATP6VOD2, ATP6VOE1, ATP6VOE2, ATP6VIA, ATP6VIB1, ATP6VIB2, ATP6VIC1,
ATP6VIC2, ATP6VID, ATP6VIE1, ATP6VIE2, ATP6VIF, ATP6VIG1, ATP6VIG2,
ATP6V1G2-DDX39B, ATP6V1G3, ATP6VIH, ATP7A, ATP7B, ATP8A1, ATP8A2, ATP8B1,
ATP8B2, ATP8B3, ATP8B4, ATP9A, ATP9B, ATPAF1, ATPAF2, ATPIF1, ATR, ATRAID,
ATRIP, ATRN, ATRNL1, ATRX, ATXN1, ATXN10, ATXN1L, ATXN2, ATXN2L, ATXN3,
ATXN3L, ATXN7, ATXN7L1, ATXN7L2, ATXN7L3, ATXN7L3B, AUH, AUNIP, AUP1,
AURKA, AURKAIP1, AURKB, AURKC, AUTS2, AVEN, AVIL, AVL9, AVP, AVPI1,
AVPRIA, AVPRIB, AVPR2, AWAT1, AWAT2, AXDND1, AXIN1, AXIN2, AXL, AZGP1,
AZI2, AZIN1, AZIN2, AZU1, B2M, B3GALNT1, B3GALNT2, B3GALT1, B3GALT2,
B3GALT4, B3GALT5, B3GALT6, B3GAT1, B3GAT2, B3GAT3, B3GLCT, B3GNT2,
B3GNT3, B3GNT4, B3GNT5, B3GNT6, B3GNT7, B3GNT8, B3GNT9, B3GNTL1,
B4GALNT1, B4GALNT2, B4GALNT3, B4GALNT4, B4GALT1, B4GALT2, B4GALT3,
B4GALT4, B4GALT5, B4GALT6, B4GALT7, B4GAT1, B9D1, B9D2, BAALC, BAAT,
BABAM1, BABAM2, BACE1, BACE2, BACH1, BACH2, BAD, BAG1, BAG2, BAG3, BAG4,
BAG5, BAG6, BAGE3, BAHCC1, BAHD1, BAIAP2, BAIAP2L1, BAIAP2L2, BAIAP3, BAK1,
BAMB1, BANF1, BANF2, BANK1, BANP, BAP1, BARD1, BARHL1, BARHL2, BARX1,
BARX2, BASP1, BATF, BATF2, BATF3, BAX, BAZIA, BAZIB, BAZ2A, BAZ2B, BBC3,
BBIP1, BBOF1, BBOX1, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, BBX,
BCAM, BCAN, BCAP29, BCAP31, BCAR1, BCAR3, BCAS1, BCAS2, BCAS3, BCAS4,
BCAT1, BCAT2, BCCIP, BCDIN3D, BCHE, BCKDHA, BCKDHB, BCKDK, BCL10, BCL11A,
BCL11B, BCL2, BCL2A1, BCL2L1, BCL2L10, BCL2L11, BCL2L12, BCL2L13, BCL2L14,
BCL2L15, BCL2L2, BCL2L2-PABPN1, BCL3, BCL6, BCL6B, BCL7A, BCL7B, BCL7C,
BCL9, BCL9L, BCLAF1, BCLAF3, BCO1, BCO2, BCOR, BCORL1, BCR, BCSIL, BDH1,
BDH2, BDKRB1, BDKRB2, BDNF, BDP1, BEAN1, BECN1, BECN2, BEGAIN, BEND2,
BEND3, BEND4, BEND5, BEND6, BEND7, BEST1, BEST2, BEST3, BEST4, BET1, BET1L,
BEX1, BEX2, BEX3, BEX4, BEX5, BFAR, BFSP1, BFSP2, BGLAP, BGN, BHLHA15,
BHLHA9, BHLHB9, BHLHE22, BHLHE23, BHLHE40, BHLHE41, BHMG1, BHMT, BHMT2,
BICC1, BICD1, BICD2, BICDL1, BICDL2, BICRA, BICRAL, BID, BIK, BIN1, BIN2, BIN3,
BIRC2, BIRC3, BIRC5, BIRC6, BIRC7, BIRC8, BIVM, BIVM-ERCC5, BLACE, BLCAP,
BLID, BLK, BLM, BLMH, BLNK, BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5,
BLOC1S5-TXNDC5, BLOC1S6, BLVRA, BLVRB, BLZF1, BMF, BMI1, BMP1, BMP10,
BMP15, BMP2, BMP2K, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8A, BMP8B, BMPER,
BMPRIA, BMPRIB, BMPR2, BMS1, BMT2, BMX, BNC1, BNC2, BNIP1, BNIP2, BNIP3,
BNIP3L, BNIPL, BOC, BOD1, BOD1L1, BOD1L2, BOK, BOLA1, BOLA2, BOLA2B, BOLA2-
SMG1P6, BOLA3, BOLL, BOP1, BORA, BORCS5, BORCS6, BORCS7, BORCS7-ASMT,
BORCS8, BORCS8-MEF2B, BPGM, BPHL, BP1, BPIFA1, BPIFA2, BPIFA3, BPIFB1, BPIFB2,
BPIFB3, BPIFB4, BPIFB6, BPIFC, BPNT1, BPTF, BPY2, BPY2B, BPY2C, BRAF, BRAP,
BRAT1, BRCA1, BRCA2, BRCC3, BRD1, BRD2, BRD3, BRD4, BRD7, BRD8, BRD9, BRDT,
BRF1, BRF2, BRI3, BRI3BP, BRICD5, BRINP1, BRINP2, BRINP3, BRIP1, BRIX1, BRK1,
BRMS1, BRMS1L, BROX, BRPF1, BRPF3, BRS3, BRSK1, BRSK2, BRWD1, BRWD3,
BSCL2, BSDC1, BSG, BSN, BSND, BSPH1, BSPRY, BST1, BST2, BSX, BTAF1, BTBD1,
BTBD10, BTBD11, BTBD16, BTBD17, BTBD18, BTBD19, BTBD2, BTBD3, BTBD6, BTBD7,
BTBD8, BTBD9, BTC, BTD, BTF3, BTF3L4, BTG1, BTG2, BTG3, BTG4, BTK, BTLA,
BTN1A1, BTN2A1, BTN2A2, BTN3A1, BTN3A2, BTN3A3, BTNL2, BTNL3, BTNL8, BTNL9,
BTRC, BUB1, BUB1B, BUB1B-PAK6, BUB3, BUD13, BUD23, BUD31, BVES, BX004987.1,
BX072566.1, BX088645.1, BX248244.1, BX248413.4, BX248415.1, BX248516.1, BX276092.9,
BYSL, BZW1, BZW2, C10orf10, C10orf105, C10orf107, C10orf113, C10orf120, C10orf126,
C10orf128, C10orf142, C10orf35, C10orf53, C10orf55, C10orf62, C10orf67, C10orf71,
C10orf76, C10orf82, C10orf88, C10orf90, C10orf95, C10orf99, C11orf1, Cllorf16, C11orf21,
C11orf24, C11orf40, C11orf42, C11orf45, C11orf49, C11orf52, C11orf53, C11orf54, C11orf57,
C11orf58, C11orf63, C11orf65, C11orf68, C11orf70, C11orf71, C11orf74, C11orf80, C11orf84,
C11orf86, C11orf87, C11orf88, C11orf91, C11orf94, C11orf95, C11orf96, C11orf97, C11orf98,
C12orf10, C12orf29, C12orf4, C12orf40, C12orf42, C12orf43, C12orf45, C12orf49, C12orf50,
C12orf54, C12orf56, C12orf57, C12orf60, C12orf65, C12orf66, C12orf71, C12orf73, C12orf74,
C12orf75, C12orf76, C13orf42, C14orf105, C14orf119, C14orf132, C14orf159, C14orf166,
C14orf177, C14orf178, C14orf180, C14orf2, C14orf28, C14orf37, C14orf39, C14orf79,
C14orf80, C14orf93, C15orf38-AP3S2, C15orf39, C15orf40, C15orf41, C15orf48, C15orf52,
C15orf53, C15orf59, C15orf61, C15orf62, C15orf65, C16orf45, C16orf46, C16orf52, C16orf54,
C16orf58, C16orf59, C16orf62, C16orf70, C16orf71, C16orf72, C16orf74, C16orf78, C16orf82,
C16orf86, C16orf87, C16orf89, C16orf90, C16orf91, C16orf92, C16orf95, C16orf96, C17orf100,
C17orf105, C17orf107, C17orf113, C17orf47, C17orf49, C17orf50, C17orf51, C17orf53,
C17orf58, C17orf62, C17orf64, C17orf67, C17orf74, C17orf75, C17orf78, C17orf80, C17orf97,
C17orf98, C17orf99, C18orf21, C18orf25, C18orf32, C18orf54, C18orf63, C18orf8, C19orf12,
C19orf18, C19orf24, C19orf25, C19orf33, C19orf35, C19orf38, C19orf44, C19orf47, C19orf48,
C19orf53, C19orf54, C19orf57, C19orf60, C19orf66, C19orf67, C19orf68, C19orf70, C19orf71,
C19orf73, C19orf81, C19orf84, CID, CIGALT1, CIGALT1C1, CIGALT1C1L, Clorf100,
Clorf105, Clorf109, Clorf112, Clorf115, Clorf116, Clorf122, Clorf123, Clorf127, Clorf131,
Clorf141, Clorf146, Clorf158, Clorf159, Clorf162, Clorf167, Clorf174, Clorf185, Clorf186,
Clorf189, Clorf194, Clorf198, Clorf21, Clorf210, Clorf216, Clorf226, Clorf228, Clorf232,
Clorf27, Clorf35, Clorf43, Clorf50, Clorf52, Clorf53, Clorf54, Clorf56, Clorf61, Clorf64,
Clorf68, Clorf74, Clorf87, Clorf94, CIQA, CIQB, CIQBP, CIQC, C1QL1, C1QL2, C1QL3,
C1QL4, CIQTNF1, CIQTNF12, CIQTNF2, CIQTNF3, CIQTNF3-AMACR, CIQTNF4,
C1QTNF5, C1QTNF6, C1QTNF7, C1QTNF8, C1QTNF9, CIQTNF9B, CIR, CIRL, CIS, C2,
C20orf141, C20orf144, C20orf173, C20orf194, C20orf196, C20orf202, C20orf204, C20orf24,
C20orf27, C20orf85, C20orf96, C21orf140, C21orf2, C21orf33, C21orf58, C21orf59, C21orf62,
C21orf91, C22orf15, C22orf23, C22orf31, C22orf39, C22orf42, C22orf46, C2CD2, C2CD2L,
C2CD3, C2CD4A, C2CD4B, C2CD4C, C2CD4D, C2CD5, C2CD6, C2orf15, C2orf16, C2orf40,
C2orf42, C2orf49, C2orf50, C2orf54, C2orf66, C2orf68, C2orf69, C2orf70, C2orf71, C2orf72,
C2orf73, C2orf74, C2orf76, C2orf78, C2orf80, C2orf81, C2orf82, C2orf83, C2orf88, C2orf91,
C3, C3AR1, C3orf14, C3orf18, C3orf20, C3orf22, C3orf30, C3orf33, C3orf35, C3orf36, C3orf38,
C3orf49, C3orf52, C3orf56, C3orf58, C3orf62, C3orf67, C3orf70, C3orf80, C3orf84, C3orf85,
C4A, C4B, C4B_2, C4BPA, C4BPB, C4orf17, C4orf19, C4orf22, C4orf26, C4orf3, C4orf32,
C4orf33, C4orf36, C4orf45, C4orf46, C4orf47, C4orf48, C4orf50, C4orf51, C5, C5AR1, C5AR2,
C5orf15, C5orf22, C5orf24, C5orf30, C5orf34, C5orf38, C5orf42, C5orf46, C5orf47, C5orf49,
C5orf51, C5orf52, C5orf56, C5orf58, C5orf60, C5orf63, C5orf67, C6, C6orf10, C6orf106,
C6orf118, C6orf120, C6orf132, C6orf136, C6orf141, C6orf15, C6orf163, C6orf201, C6orf203,
C6orf222, C6orf223, C6orf226, C6orf229, C6orf47, C6orf48, C6orf52, C6orf58, C6orf62,
C6orf89, C7, C7orf25, C7orf26, C7orf31, C7orf33, C7orf34, C7orf43, C7orf49, C7orf50,
C7orf55-LUC7L2, C7orf57, C7orf61, C7orf72, C7orf73, C7orf77, C8A, C8B, C8G, C8orf22,
C8orf33, C8orf34, C8orf37, C8orf4, C8orf44, C8orf44-SGK3, C8orf46, C8orf48, C8orf58,
C8orf59, C8orf74, C8orf76, C8orf82, C8orf86, C8orf88, C8orf89, C9, C9orf116, C9orf129,
C9orf131, C9orf135, C9orf152, C9orf153, C9orf16, C9orf172, C9orf24, C9orf3, C9orf40,
C9orf43, C9orf47, C9orf50, C9orf57, C9orf64, C9orf66, C9orf72, C9orf78, C9orf84, C9orf85,
C9orf92, CA1, CA10, CA11, CA12, CA13, CA14, CA2, CA3, CA4, CASA, CA5B, CA6, CA7,
CA8, CA9, CAAP1, CAB39, CAB39L, CABIN1, CABLES1, CABLES2, CABP1, CABP2,
CABP4, CABP5, CABP7, CABS1, CABYR, CACFD1, CACHD1, CACNA1A, CACNA1B,
CACNA1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, CACNA1I,
CACNA1S, CACNA2D1, CACNA2D2, CACNA2D3, CACNA2D4, CACNB1, CACNB2,
CACNB3, CACNB4, CACNG1, CACNG2, CACNG3, CACNG4, CACNG5, CACNG6,
CACNG7, CACNG8, CACTIN, CACUL1, CACYBP, CAD, CADM1, CADM2, CADM3,
CADM4, CADPS, CADPS2, CAGE1, CALB1, CALB2, CALCA, CALCB, CALCOCO1,
CALCOCO2, CALCR, CALCRL, CALD1, CALHM1, CALHM2, CALHM3, CALM1, CALM2,
CALM3, CALML3, CALML4, CALML5, CALML6, CALN1, CALR, CALR3, CALU, CALY,
CAMK1, CAMKID, CAMKIG, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK2N1,
CAMK2N2, CAMK4, CAMKK1, CAMKK2, CAMKMT, CAMKV, CAMLG, CAMP,
CAMSAP1, CAMSAP2, CAMSAP3, CAMTA1, CAMTA2, CAND1, CAND2, CANT1, CANX,
CAP1, CAP2, CAPG, CAPN1, CAPN10, CAPN11, CAPN12, CAPN13, CAPN14, CAPN15,
CAPN2, CAPN3, CAPN5, CAPN6, CAPN7, CAPN8, CAPN9, CAPNS1, CAPNS2, CAPRIN1,
CAPRIN2, CAPS, CAPS2, CAPSL, CAPZA1, CAPZA2, CAPZA3, CAPZB, CARD10,
CARD11, CARD14, CARD16, CARD17, CARD18, CARD19, CARD6, CARD8, CARD9,
CARF, CARHSP1, CARM1, CARM1L1, CARM1L2, CARM1L3, CARNMT1, CARNS1, CARS,
CARS2, CARTPT, CASC1, CASC10, CASC3, CASC4, CASD1, CASK, CASKIN1, CASKIN2,
CASP1, CASP10, CASP12, CASP14, CASP2, CASP3, CASP4, CASP5, CASP6, CASP7,
CASP8, CASP8AP2, CASP9, CASQ1, CASQ2, CASR, CASS4, CAST, CASTOR1, CASTOR2,
CASZ1, CAT, CATIP, CATSPER1, CATSPER2, CATSPER3, CATSPER4, CATSPERB,
CATSPERD, CATSPERE, CATSPERG, CATSPERZ, CAV1, CAV2, CAV3, CAVIN1,
CAVIN2, CAVIN3, CAVIN4, CBARP, CBFA2T2, CBFA2T3, CBFB, CBL, CBLB, CBLC,
CBLL1, CBLN1, CBLN2, CBLN3, CBLN4, CBR1, CBR3, CBR4, CBS, CBSL, CBWD1,
CBWD2, CBWD3, CBWD5, CBWD6, CBX1, CBX2, CBX3, CBX4, CBX5, CBX6, CBX7,
CBX8, CBY1, CBY3, CC2D1A, CC2D1B, CC2D2A, CC2D2B, CCAR1, CCAR2, CCBE1,
CCDC102A, CCDC102B, CCDC103, CCDC105, CCDC106, CCDC107, CCDC110, CCDC112,
CCDC113, CCDC114, CCDC115, CCDC116, CCDC117, CCDC12, CCDC120, CCDC121,
CCDC122, CCDC124, CCDC125, CCDC126, CCDC127, CCDC129, CCDC13, CCDC130,
CCDC134, CCDC136, CCDC137, CCDC138, CCDC14, CCDC140, CCDC141, CCDC142,
CCDC144A, CCDC144NL, CCDC146, CCDC148, CCDC149, CCDC15, CCDC150, CCDC151,
CCDC152, CCDC153, CCDC154, CCDC155, CCDC157, CCDC158, CCDC159, CCDC160,
CCDC163, CCDC166, CCDC167, CCDC168, CCDC169, CCDC169-SOHLH2, CCDC17,
CCDC170, CCDC171, CCDC172, CCDC173, CCDC174, CCDC175, CCDC177, CCDC178,
CCDC179, CCDC18, CCDC180, CCDC181, CCDC182, CCDC183, CCDC184, CCDC185,
CCDC186, CCDC187, CCDC188, CCDC189, CCDC190, CCDC191, CCDC192, CCDC194,
CCDC195, CCDC196, CCDC197, CCDC22, CCDC24, CCDC25, CCDC27, CCDC28A,
CCDC28B, CCDC3, CCDC30, CCDC32, CCDC33, CCDC34, CCDC36, CCDC38, CCDC39,
CCDC40, CCDC42, CCDC43, CCDC47, CCDC50, CCDC51, CCDC54, CCDC57, CCDC58,
CCDC59, CCDC6, CCDC60, CCDC61, CCDC62, CCDC63, CCDC65, CCDC66, CCDC68,
CCDC69, CCDC7, CCDC70, CCDC71, CCDC71L, CCDC73, CCDC74A, CCDC74B, CCDC77,
CCDC78, CCDC8, CCDC80, CCDC81, CCDC82, CCDC83, CCDC84, CCDC85A, CCDC85B,
CCDC85C, CCDC86, CCDC87, CCDC88A, CCDC88B, CCDC88C, CCDC89, CCDC9,
CCDC90B, CCDC91, CCDC92, CCDC93, CCDC94, CCDC96, CCDC97, CCER1, CCER2,
CCHCR1, CCIN, CCK, CCKAR, CCKBR, CCL1, CCL11, CCL13, CCL14, CCL15, CCL15-
CCL14, CCL16, CCL17, CCL18, CCL19, CCL2, CCL20, CCL21, CCL22, CCL23, CCL24,
CCL25, CCL26, CCL27, CCL28, CCL3, CCL3L1, CCL3L3, CCL4, CCL4L2, CCL5, CCL7,
CCL8, CCM2, CCM2L, CCNA1, CCNA2, CCNB1, CCNB1IP1, CCNB2, CCNB3, CCNC,
CCND1, CCND2, CCND3, CCNDBP1, CCNE1, CCNE2, CCNF, CCNG1, CCNG2, CCNH,
CCN1, CCNI2, CCNJ, CCNJL, CCNK, CCNL1, CCNL2, CCNO, CCNT1, CCNT2, CCNY,
CCNYL1, CCP110, CCPG1, CCR1, CCR10, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8,
CCR9, CCRL2, CCS, CCSAP, CCSER1, CCSER2, CCT2, CCT3, CCT4, CCT5, CCT6A,
CCT6B, CCT7, CCT8, CCT8L2, CCZ1, CCZ1B, CD101, CD109, CD14, CD151, CD160,
CD163, CD163L1, CD164, CD164L2, CD177, CD180, CD19, CD1A, CD1B, CD1C, CD1D,
CD1E, CD2, CD200, CD200R1, CD200R1L, CD207, CD209, CD22, CD226, CD24, CD244,
CD247, CD248, CD27, CD274, CD276, CD28, CD2AP, CD2BP2, CD300A, CD300C, CD300E,
CD300LB, CD300LD, CD300LF, CD300LG, CD302, CD320, CD33, CD34, CD36, CD37,
CD38, CD3D, CD3E, CD3EAP, CD3G, CD4, CD40, CD40LG, CD44, CD46, CD47, CD48, CD5,
CD52, CD53, CD55, CD58, CD59, CD5L, CD6, CD63, CD68, CD69, CD7, CD70, CD72, CD74,
CD79A, CD79B, CD80, CD81, CD82, CD83, CD84, CD86, CD8A, CD8B, CD9, CD93, CD96,
CD99, CD99L2, CDA, CDADC1, CDAN1, CDC123, CDC14A, CDC14B, CDC16, CDC20,
CDC20B, CDC23, CDC25A, CDC25B, CDC25C, CDC26, CDC27, CDC34, CDC37, CDC37L1,
CDC40, CDC42, CDC42BPA, CDC42BPB, CDC42BPG, CDC42EP1, CDC42EP2, CDC42EP3,
CDC42EP4, CDC42EP5, CDC42SE1, CDC42SE2, CDC45, CDC5L, CDC6, CDC7, CDC73,
CDCA2, CDCA3, CDCA4, CDCA5, CDCA7, CDCA7L, CDCA8, CDCP1, CDCP2, CDH1,
CDH10, CDH11, CDH12, CDH13, CDH15, CDH16, CDH17, CDH18, CDH19, CDH2, CDH20,
CDH22, CDH23, CDH24, CDH26, CDH3, CDH4, CDH5, CDH6, CDH7, CDH8, CDH9,
CDHR1, CDHR2, CDHR3, CDHR4, CDHR5, CDIP1, CDIPT, CDK1, CDK10, CDK11A,
CDK11B, CDK12, CDK13, CDK14, CDK15, CDK16, CDK17, CDK18, CDK19, CDK2,
CDK20, CDK2AP1, CDK2AP2, CDK3, CDK4, CDK5, CDK5R1, CDK5R2, CDK5RAP1,
CDK5RAP2, CDK5RAP3, CDK6, CDK7, CDK8, CDK9, CDKAL1, CDKL1, CDKL2, CDKL3,
CDKL4, CDKL5, CDKNIA, CDKNIB, CDKNIC, CDKN2A, CDKN2AIP, CDKN2AIPNL,
CDKN2B, CDKN2C, CDKN2D, CDKN3, CDNF, CDO1, CDON, CDPF1, CDR1, CDR2,
CDR2L, CDRT1, CDRT15, CDRT15L2, CDRT4, CDS1, CDS2, CDSN, CDT1, CDV3, CDX1,
CDX2, CDX4, CDY1, CDY1B, CDY2A, CDY2B, CDYL, CDYL2, CEACAM1, CEACAM16,
CEACAM19, CEACAM20, CEACAM21, CEACAM3, CEACAM4, CEACAM5, CEACAM6,
CEACAM7, CEACAM8, CEBPA, CEBPB, CEBPD, CEBPE, CEBPG, CEBPZ, CEBPZOS,
CECR2, CEL, CELA1, CELA2A, CELA2B, CELA3A, CELA3B, CELF1, CELF2, CELF3,
CELF4, CELF5, CELF6, CELSR1, CELSR2, CELSR3, CEMIP, CEMP1, CEND1, CENPA,
CENPB, CENPBD1, CENPC, CENPE, CENPF, CENPH, CENPI, CENPJ, CENPK, CENPL,
CENPM, CENPN, CENPO, CENPP, CENPQ, CENPS, CENPS-CORT, CENPT, CENPU,
CENPV, CENPVL1, CENPVL2, CENPVL3, CENPW, CENPX, CEP104, CEP112, CEP120,
CEP126, CEP128, CEP131, CEP135, CEP152, CEP162, CEP164, CEP170, CEP170B, CEP19,
CEP192, CEP250, CEP290, CEP295, CEP295NL, CEP350, CEP41, CEP44, CEP55, CEP57,
CEP57L1, CEP63, CEP68, CEP70, CEP72, CEP76, CEP78, CEP83, CEP85, CEP85L, CEP89,
CEP95, CEP97, CEPT1, CER1, CERCAM, CERK, CERKL, CERS1, CERS2, CERS3, CERS4,
CERS5, CERS6, CES1, CES2, CES3, CES4A, CES5A, CETN1, CETN2, CETN3, CETP,
CFAP100, CFAP126, CFAP157, CFAP161, CFAP20, CFAP206, CFAP221, CFAP36, CFAP43,
CFAP44, CFAP45, CFAP46, CFAP47, CFAP52, CFAP53, CFAP54, CFAP57, CFAP58,
CFAP61, CFAP65, CFAP69, CFAP70, CFAP73, CFAP74, CFAP77, CFAP97, CFAP99, CFB,
CFC1, CFC1B, CFD, CFDP1, CFH, CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, CFI, CFL1,
CFL2, CFLAR, CFP, CFTR, CGA, CGB1, CGB2, CGB3, CGB5, CGB7, CGB8, CGGBP1, CGN,
CGNL1, CGREF1, CGRRF1, CH25H, CHAC1, CHAC2, CHAD, CHADL, CHAF1A, CHAFIB,
CHAMP1, CHAT, CHCHD1, CHCHD10, CHCHD2, CHCHD3, CHCHD4, CHCHD5,
CHCHD6, CHCHD7, CHD1, CHD1L, CHD2, CHD3, CHD4, CHD5, CHD6, CHD7, CHD8,
CHD9, CHDH, CHEK1, CHEK2, CHERP, CHFR, CHGA, CHGB, CHI3L1, CHI3L2, CHIA,
CHIC1, CHIC2, CHID1, CHIT1, CHKA, CHKB, CHKB-CPTIB, CHL1, CHM, CHML,
CHMP1A, CHMP1B, CHMP2A, CHMP2B, CHMP3, CHMP4A, CHMP4B, CHMP4C, CHMP5,
CHMP6, CHMP7, CHN1, CHN2, CHODL, CHORDC1, CHP1, CHP2, CHPF, CHPF2, CHPT1,
CHRAC1, CHRD, CHRDL1, CHRDL2, CHRFAM7A, CHRM1, CHRM2, CHRM3, CHRM4,
CHRM5, CHRNA1, CHRNA10, CHRNA2, CHRNA3, CHRNA4, CHRNA5, CHRNA6,
CHRNA7, CHRNA9, CHRNB1, CHRNB2, CHRNB3, CHRNB4, CHRND, CHRNE, CHRNG,
CHST1, CHST10, CHST11, CHST12, CHST13, CHST14, CHST15, CHST2, CHST3, CHST4,
CHST5, CHST6, CHST7, CHST8, CHST9, CHSY1, CHSY3, CHTF18, CHTF8, CHTOP, CHUK,
CHURC1, CHURC1-FNTB, CIAO1, CIAPIN1, CIART, CIB1, CIB2, CIB3, CIB4, CIC, CIDEA,
CIDEB, CIDEC, CIITA, CILP, CILP2, CINP, CIPC, CIR1, CIRBP, CISD1, CISD2, CISD3,
CISH, CIT, CITED1, CITED2, CITED4, CIZ1, CKAP2, CKAP2L, CKAP4, CKAP5, CKB,
CKLF, CKLF-CMTM1, CKM, CKMTIA, CKMTIB, CKMT2, CKS1B, CKS2, CLASP1,
CLASP2, CLASRP, CLC, CLCA1, CLCA2, CLCA4, CLCC1, CLCF1, CLCN1, CLCN2,
CLCN3, CLCN4, CLCN5, CLCN6, CLCN7, CLCNKA, CLCNKB, CLDN1, CLDN10, CLDN11,
CLDN12, CLDN14, CLDN15, CLDN16, CLDN17, CLDN18, CLDN19, CLDN2, CLDN20,
CLDN22, CLDN23, CLDN24, CLDN25, CLDN3, CLDN34, CLDN4, CLDN5, CLDN6, CLDN7,
CLDN8, CLDN9, CLDND1, CLDND2, CLEC10A, CLEC11A, CLEC12A, CLEC12B,
CLEC14A, CLEC16A, CLEC17A, CLEC18A, CLEC18B, CLEC18C, CLEC19A, CLECIA,
CLEC1B, CLEC20A, CLEC2A, CLEC2B, CLEC2D, CLEC2L, CLEC3A, CLEC3B, CLEC4A,
CLEC4C, CLEC4D, CLEC4E, CLEC4F, CLEC4G, CLEC4M, CLEC5A, CLEC6A, CLEC7A,
CLEC9A, CLECL1, CLGN, CLHC1, CLIC1, CLIC2, CLIC3, CLIC4, CLIC5, CLIC6, CLINT1,
CLIP1, CLIP2, CLIP3, CLIP4, CLK1, CLK2, CLK3, CLK4, CLLU1, CLLUIOS, CLMN, CLMP,
CLN3, CLN5, CLN6, CLN8, CLNK, CLNSIA, CLOCK, CLP1, CLPB, CLPP, CLPS, CLPSL1,
CLPSL2, CLPTM1, CLPTM1L, CLPX, CLRN1, CLRN2, CLRN3, CLSPN, CLSTN1, CLSTN2,
CLSTN3, CLTA, CLTB, CLTC, CLTCL1, CLU, CLUAP1, CLUH, CLUL1, CLVS1, CLVS2,
CLYBL, CMA1, CMAS, CMBL, CMC1, CMC2, CMC4, CMIP, CMKLR1, CMPK1, CMPK2,
CMSS1, CMTM1, CMTM2, CMTM3, CMTM4, CMTM5, CMTM6, CMTM7, CMTM8,
CMTR1, CMTR2, CMYA5, CNBD1, CNBD2, CNBP, CNDP1, CNDP2, CNEPIR1, CNFN,
CNGA1, CNGA2, CNGA3, CNGA4, CNGB1, CNGB3, CNIH1, CNIH2, CNIH3, CNIH4,
CNKSR1, CNKSR2, CNKSR3, CNMD, CNN1, CNN2, CNN3, CNNM1, CNNM2, CNNM3,
CNNM4, CNOT1, CNOT10, CNOT11, CNOT2, CNOT3, CNOT4, CNOT6, CNOT6L, CNOT7,
CNOT8, CNOT9, CNP, CNPPD1, CNPY1, CNPY2, CNPY3, CNPY4, CNR1, CNR2, CNRIP1,
CNST, CNTD1, CNTD2, CNTF, CNTFR, CNTLN, CNTN1, CNTN2, CNTN3, CNTN4, CNTN5,
CNTN6, CNTNAP1, CNTNAP2, CNTNAP3, CNTNAP3B, CNTNAP4, CNTNAP5, CNTRL,
CNTROB, COA1, COA3, COA4, COA5, COA6, COA7, COASY, COBL, COBLL1, COCH,
COG1, COG2, COG3, COG4, COG5, COG6, COG7, COG8, COIL, COL10A1, COL11A1,
COL11A2, COL12A1, COL13A1, COL14A1, COL15A1, COL16A1, COL17A1, COL18A1,
COL19A1, COL1A1, COL1A2, COL20A1, COL21A1, COL22A1, COL23A1, COL24A1,
COL25A1, COL26A1, COL27A1, COL28A1, COL2A1, COL3A1, COL4A1, COL4A2,
COL4A3, COL4A3BP, COL4A4, COL4A5, COL4A6, COL5A1, COL5A2, COL5A3, COL6A1,
COL6A2, COL6A3, COL6A5, COL6A6, COL7A1, COL8A1, COL8A2, COL9A1, COL9A2,
COL9A3, COLCA2, COLEC10, COLEC11, COLEC12, COLGALT1, COLGALT2, COLQ,
COMMD1, COMMD10, COMMD2, COMMD3, COMMD3-BMI1, COMMD4, COMMD5,
COMMD6, COMMD7, COMMD8, COMMD9, COMP, COMT, COMTD1, COPA, COPB1,
COPB2, COPE, COPG1, COPG2, COPRS, COPS2, COPS3, COPS4, COPS5, COPS6, COPS7A,
COPS7B, COPS8, COPS9, COPZ1, COPZ2, COQ10A, COQ10B, COQ2, COQ3, COQ4, COQ5,
COQ6, COQ7, COQ8A, COQ8B, COQ9, CORIN, CORO1A, CORO1B, CORO1C, CORO2A,
CORO2B, CORO6, CORO7, CORO7-PAM16, CORT, COTL1, COX10, COX11, COX14,
COX15, COX16, COX17, COX18, COX19, COX20, COX411, COX412, COX5A, COX5B,
COX6A1, COX6A2, COX6B1, COX6B2, COX6C, COX7A1, COX7A2, COX7A2L, COX7B,
COX7B2, COX7C, COX8A, COX8C, CP, CPA1, CPA2, CPA3, CPA4, CPA5, CPA6, CPAMD8,
CPB1, CPB2, CPD, CPE, CPEB1, CPEB2, CPEB3, CPEB4, CPED1, CPLX1, CPLX2, CPLX3,
CPLX4, CPM, CPN1, CPN2, CPNE1, CPNE2, CPNE3, CPNE4, CPNE5, CPNE6, CPNE7,
CPNE8, CPNE9, CPO, CPOX, CPPED1, CPQ, CPS1, CPSF1, CPSF2, CPSF3, CPSF4, CPSF4L,
CPSF6, CPSF7, CPTIA, CPT1B, CPTIC, CPT2, CPTP, CPVL, CPXCR1, CPXM1, CPXM2,
CPZ, CR1, CR1L, CR2, CR354443.1, CR354443.2, CR388407.3, CR547123.3, CR753842.1,
CR753845.2, CR759815.2, CR788250.1, CR847794.2, CR854858.1, CR933783.3, CR936239.1,
CRABP1, CRABP2, CRACR2A, CRACR2B, CRADD, CRAMP1, CRAT, CRB1, CRB2, CRB3,
CRBN, CRCP, CRCT1, CREB1, CREB3, CREB3L1, CREB3L2, CREB3L3, CREB3L4, CREB5,
CREBBP, CREBL2, CREBRF, CREBZF, CREG1, CREG2, CRELD1, CRELD2, CREM, CRH,
CRHBP, CRHR1, CRHR2, CRIM1, CRIP1, CRIP2, CRIP3, CRIPT, CRISP1, CRISP2, CRISP3,
CRISPLD1, CRISPLD2, CRK, CRKL, CRLF1, CRLF2, CRLF3, CRLS1, CRMP1, CRNKL1,
CRNN, CROCC, CROCC2, CROT, CRP, CRTAC1, CRTAM, CRTAP, CRTC1, CRTC2,
CRTC3, CRX, CRY1, CRY2, CRYAA, CRYAB, CRYBA1, CRYBA2, CRYBA4, CRYBB1,
CRYBB2, CRYBB3, CRYBG1, CRYBG2, CRYBG3, CRYGA, CRYGB, CRYGC, CRYGD,
CRYGN, CRYGS, CRYL1, CRYM, CRYZ, CRYZL1, CS, CSAD, CSAG1, CSAG2, CSAG3,
CSDC2, CSDE1, CSE1L, CSF1, CSFIR, CSF2, CSF2RA, CSF2RB, CSF3, CSF3R,
CSGALNACT1, CSGALNACT2, CSH1, CSH2, CSHL1, CSK, CSMD1, CSMD2, CSMD3,
CSN1S1, CSN2, CSN3, CSNK1A1, CSNK1A1L, CSNK1D, CSNK1E, CSNK1G1, CSNK1G2,
CSNK1G3, CSNK2A1, CSNK2A2, CSNK2A3, CSNK2B, CSPG4, CSPG5, CSPP1, CSRNP1,
CSRNP2, CSRNP3, CSRP1, CSRP2, CSRP3, CST1, CST11, CST2, CST3, CST4, CST5, CST6,
CST7, CST8, CST9, CST9L, CSTA, CSTB, CSTF1, CSTF2, CSTF2T, CSTF3, CSTL1, CT45A1,
CT45A10, CT45A2, CT45A3, CT45A5, CT45A6, CT45A7, CT45A8, CT45A9, CT476828.1,
CT476828.10, CT476828.11, CT476828.12, CT476828.13, CT476828.14, CT476828.15,
CT476828.16, CT476828.17, CT476828.18, CT476828.19, CT476828.2, CT476828.20,
CT476828.21, CT476828.22, CT476828.3, CT476828.4, CT476828.5, CT476828.6,
CT476828.7, CT476828.8, CT476828.9, CT47A1, CT47A10, CT47A11, CT47A12, CT47A2,
CT47A3, CT47A4, CT47A5, CT47A6, CT47A7, CT47A8, CT47A9, CT47B1, CT55, CT62,
CT83, CTAGIA, CTAGIB, CTAG2, CTAGE1, CTAGE15, CTAGE4, CTAGE5, CTAGE6,
CTAGE8, CTAGE9, CTBP1, CTBP2, CTBS, CTC1, CTCF, CTCFL, CTDNEP1, CTDP1,
CTDSP1, CTDSP2, CTDSPL, CTDSPL2, CTF1, CTGF, CTH, CTHRC1, CTIF, CTLA4,
CTNNA1, CTNNA2, CTNNA3, CTNNAL1, CTNNB1, CTNNBIP1, CTNNBL1, CTNND1,
CTNND2, CTNS, CTPS1, CTPS2, CTR9, CTRB1, CTRB2, CTRC, CTRL, CTSA, CTSB, CTSC,
CTSD, CTSE, CTSF, CTSG, CTSH, CTSK, CTSL, CTSO, CTSS, CTSV, CTSW, CTSZ, CTTN,
CTTNBP2, CTTNBP2NL, CTU1, CTU2, CTXN1, CTXN2, CTXN3, CTXND1, CU464060.1,
CU633846.1, CU633980.1, CU633980.2, CU639417.1, CU639417.2, CUBN, CUEDC1,
CUEDC2, CUL1, CUL2, CUL3, CUL4A, CUL4B, CUL5, CUL7, CUL9, CUTA, CUTC, CUX1,
CUX2, CUZD1, CWC15, CWC22, CWC25, CWC27, CWF19L1, CWF19L2, CWH43, CX3CL1,
CX3CR1, CXADR, CXCL1, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14, CXCL16,
CXCL17, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, CXCL9, CXCR1, CXCR2, CXCR3,
CXCR4, CXCR5, CXCR6, CXorf21, CXorf36, CXorf38, CXorf40A, CXorf40B, CXorf49,
CXorf49B, CXorf51A, CXorf51B, CXorf56, CXorf57, CXorf58, CXorf65, CXorf66, CXorf67,
CXXC1, CXXC4, CXXC5, CYB561, CYB561A3, CYB561D1, CYB561D2, CYB5A, CYB5B,
CYB5D1, CYB5D2, CYB5R1, CYB5R2, CYB5R3, CYBER4, CYBERL, CYBA, CYBB,
CYBRD1, CYC1, CYCS, CYFIP1, CYFIP2, CYGB, CYHR1, CYLC1, CYLC2, CYLD,
CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1, CYP1A1, CYP1A2, CYP1B1,
CYP20A1, CYP21A2, CYP24A1, CYP26A1, CYP26B1, CYP26C1, CYP27A1, CYP27B1,
CYP27C1, CYP2A13, CYP2A6, CYP2A7, CYP2B6, CYP2C18, CYP2C19, CYP2C8, CYP2C9,
CYP2D6, CYP2D7, CYP2E1, CYP2F1, CYP2J2, CYP2R1, CYP2S1, CYP2U1, CYP2W1,
CYP39A1, CYP3A4, CYP3A43, CYP3A5, CYP3A7, CYP3A7-CYP3A51P, CYP46A1,
CYP4A11, CYP4A22, CYP4B1, CYP4F11, CYP4F12, CYP4F2, CYP4F22, CYP4F3, CYP4F8,
CYP4V2, CYP4X1, CYP4Z1, CYP51A1, CYP7A1, CYP7B1, CYP8B1, CYR61, CYS1,
CYSLTR1, CYSLTR2, CYSRT1, CYSTM1, CYTH1, CYTH2, CYTH3, CYTH4, CYTIP,
CYTL1, CYYR1, D2HGDH, DAAM1, DAAM2, DAB1, DAB2, DAB2IP, DACH1, DACH2,
DACT1, DACT2, DACT3, DAD1, DAG1, DAGLA, DAGLB, DALRD3, DAND5, DAO, DAOA,
DAP, DAP3, DAPK1, DAPK2, DAPK3, DAPL1, DAPP1, DARS, DARS2, DAW1, DAXX,
DAZ1, DAZ2, DAZ3, DAZ4, DAZAP1, DAZAP2, DAZL, DBF4, DBF4B, DBH, DBI, DBN1,
DBNDD1, DBNDD2, DBNL, DBP, DBR1, DBT, DBX1, DBX2, DCAF1, DCAF10, DCAF11,
DCAF12, DCAF12L1, DCAF12L2, DCAF13, DCAF15, DCAF16, DCAF17, DCAF4,
DCAF4L1, DCAF4L2, DCAF5, DCAF6, DCAF7, DCAF8, DCAF8L1, DCAF8L2, DCAKD,
DCANP1, DCBLD1, DCBLD2, DCC, DCD, DCDC1, DCDC2, DCDC2B, DCDC2C, DCHS1,
DCHS2, DCK, DCLK1, DCLK2, DCLK3, DCLREIA, DCLREIB, DCLREIC, DCN, DCP1A,
DCP1B, DCP2, DCPS, DCST1, DCST2, DCSTAMP, DCT, DCTD, DCTN1, DCTN2, DCTN3,
DCTN4, DCTN5, DCTN6, DCTPP1, DCUNID1, DCUNID2, DCUNID3, DCUNID4,
DCUNID5, DCX, DCXR, DDA1, DDAH1, DDAH2, DDB1, DDB2, DDC, DDHD1, DDHD2,
DDI1, DDI2, DDIAS, DDIT3, DDIT4, DDIT4L, DDN, DDO, DDOST, DDR1, DDR2, DDRGK1,
DDT, DDTL, DDX1, DDX10, DDX11, DDX17, DDX18, DDX19A, DDX19B, DDX20, DDX21,
DDX23, DDX24, DDX25, DDX27, DDX28, DDX31, DDX39A, DDX39B, DDX3X, DDX3Y,
DDX4, DDX41, DDX42, DDX43, DDX46, DDX47, DDX49, DDX5, DDX50, DDX51, DDX52,
DDX53, DDX54, DDX55, DDX56, DDX58, DDX59, DDX6, DDX60, DDX60L, DEAF1, DEC1,
DECR1, DECR2, DEDD, DEDD2, DEF6, DEF8, DEFA1, DEFAIB, DEFA3, DEFA4, DEFA5,
DEFA6, DEFB1, DEFB103A, DEFB103B, DEFB104A, DEFB104B, DEFB105A, DEFB105B,
DEFB106A, DEFB106B, DEFB107A, DEFB107B, DEFB108B, DEFB110, DEFB112,
DEFB113, DEFB114, DEFB115, DEFB116, DEFB118, DEFB119, DEFB121, DEFB123,
DEFB124, DEFB125, DEFB126, DEFB127, DEFB128, DEFB129, DEFB130A, DEFB130B,
DEFB131A, DEFB131B, DEFB132, DEFB133, DEFB134, DEFB135, DEFB136, DEFB4A,
DEFB4B, DEGS1, DEGS2, DEK, DENNDIA, DENNDIB, DENNDIC, DENND2A,
DENND2C, DENND2D, DENND3, DENND4A, DENND4B, DENND4C, DENND5A,
DENND5B, DENND6A, DENND6B, DENR, DEPDC1, DEPDC1B, DEPDC4, DEPDC5,
DEPDC7, DEPTOR, DERA, DERL1, DERL2, DERL3, DES, DESI1, DESI2, DET1, DEUP1,
DEX1, DFFA, DFFB, DFNA5, DFNB59, DGAT1, DGAT2, DGAT2L6, DGCR2, DGCR6,
DGCR6L, DGCR8, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKI, DGKK, DGKQ,
DGKZ, DGUOK, DHCR24, DHCR7, DHDDS, DHDH, DHFR, DHFR2, DHH, DHODH, DHPS,
DHRS1, DHRS11, DHRS12, DHRS13, DHRS2, DHRS3, DHRS4, DHRS4L2, DHRS7,
DHRS7B, DHRS7C, DHRS9, DHRSX, DHTKD1, DHX15, DHX16, DHX29, DHX30, DHX32,
DHX33, DHX34, DHX35, DHX36, DHX37, DHX38, DHX40, DHX57, DHX58, DHX8, DHX9,
DIABLO, DIAPH1, DIAPH2, DIAPH3, DICER1, DIDO1, DIEXF, DIMT1, DIO1, DIO2, DIO3,
DIP2A, DIP2B, DIP2C, DIRAS1, DIRAS2, DIRAS3, DIRC1, DIRC2, DIRC3, DIS3, DIS3L,
DIS3L2, DISC1, DISP1, DISP2, DISP3, DIXDC1, DKC1, DKK1, DKK2, DKK3, DKK4,
DKKL1, DLAT, DLC1, DLD, DLEC1, DLEU7, DLG1, DLG2, DLG3, DLG4, DLG5, DLGAP1,
DLGAP2, DLGAP3, DLGAP4, DLGAP5, DLK1, DLK2, DLL1, DLL3, DLL4, DLST, DLX1,
DLX2, DLX3, DLX4, DLX5, DLX6, DMAC1, DMAC2, DMAP1, DMBT1, DMBX1, DMC1,
DMD, DMGDH, DMKN, DMP1, DMPK, DMRT1, DMRT2, DMRT3, DMRTA1, DMRTA2,
DMRTB1, DMRTC1, DMRTC1B, DMRTC2, DMTF1, DMTN, DMWD, DMXL1, DMXL2,
DNA2, DNAAF1, DNAAF2, DNAAF3, DNAAF4, DNAAF5, DNAH1, DNAH10, DNAH10OS,
DNAH11, DNAH12, DNAH14, DNAH17, DNAH2, DNAH3, DNAH5, DNAH6, DNAH7,
DNAH8, DNAH9, DNAI1, DNAI2, DNAJA1, DNAJA2, DNAJA3, DNAJA4, DNAJB1,
DNAJB11, DNAJB12, DNAJB13, DNAJB14, DNAJB2, DNAJB4, DNAJB5, DNAJB6,
DNAJB7, DNAJB8, DNAJB9, DNAJC1, DNAJC10, DNAJC11, DNAJC12, DNAJC13,
DNAJC14, DNAJC15, DNAJC16, DNAJC17, DNAJC18, DNAJC19, DNAJC2, DNAJC21,
DNAJC22, DNAJC24, DNAJC25, DNAJC25-GNG10, DNAJC27, DNAJC28, DNAJC3,
DNAJC30, DNAJC4, DNAJC5, DNAJC5B, DNAJC5G, DNAJC6, DNAJC7, DNAJC8,
DNAJC9, DNAL1, DNAL4, DNALI1, DNASE1, DNASEIL1, DNASE1L2, DNASE1L3,
DNASE2, DNASE2B, DND1, DNER, DNHD1, DNLZ, DNM1, DNM1L, DNM2, DNM3,
DNMBP, DNMT1, DNMT3A, DNMT3B, DNMT3L, DNPEP, DNPH1, DNTT, DNTTIP1,
DNTTIP2, DOC2A, DOC2B, DOCK1, DOCK10, DOCK11, DOCK2, DOCK3, DOCK4,
DOCK5, DOCK6, DOCK7, DOCK8, DOCK9, DOHH, DOK1, DOK2, DOK3, DOK4, DOK5,
DOK6, DOK7, DOLK, DOLPP1, DONSON, DOPEY1, DOPEY2, DOT1L, DPAGT1, DPCD,
DPCR1, DPEP1, DPEP2, DPEP3, DPF1, DPF2, DPF3, DPH1, DPH2, DPH3, DPH5, DPH6,
DPH7, DPM1, DPM2, DPM3, DPP10, DPP3, DPP4, DPP6, DPP7, DPP8, DPP9, DPPA2, DPPA3,
DPPA4, DPPA5, DPRX, DPT, DPY19L1, DPY19L2, DPY19L3, DPY19L4, DPY30, DPYD,
DPYS, DPYSL2, DPYSL3, DPYSL4, DPYSL5, DQX1, DR1, DRAM1, DRAM2, DRAP1,
DRAXIN, DRC1, DRC3, DRC7, DRD1, DRD2, DRD3, DRD4, DRD5, DRG1, DRG2, DRGX,
DRICH1, DROSHA, DRP2, DSC1, DSC2, DSC3, DSCAM, DSCAML1, DSCC1, DSCR3,
DSCR4, DSCR8, DSE, DSEL, DSG1, DSG2, DSG3, DSG4, DSN1, DSP, DSPP, DST, DSTN,
DSTYK, DTD1, DTD2, DTHD1, DTL, DTNA, DTNB, DTNBP1, DTWD1, DTWD2, DTX1,
DTX2, DTX3, DTX3L, DTX4, DTYMK, DUOX1, DUOX2, DUOXA1, DUOXA2, DUPD1,
DUS1L, DUS2, DUS3L, DUS4L, DUSP1, DUSP10, DUSP11, DUSP12, DUSP13, DUSP14,
DUSP15, DUSP16, DUSP18, DUSP19, DUSP2, DUSP21, DUSP22, DUSP23, DUSP26,
DUSP27, DUSP28, DUSP3, DUSP4, DUSP5, DUSP6, DUSP7, DUSP8, DUSP9, DUT, DUX4,
DUXA, DUXB, DVL1, DVL2, DVL3, DWORF, DXO, DYDC1, DYDC2, DYM, DYNAP,
DYNC1H1, DYNC1I1, DYNC112, DYNC1LI1, DYNC1LI2, DYNC2H1, DYNC2LI1, DYNLL1,
DYNLL2, DYNLRB1, DYNLRB2, DYNLT1, DYNLT3, DYRKIA, DYRKIB, DYRK2,
DYRK3, DYRK4, DYSF, DYTN, DZANK1, DZIP1, DZIP1L, DZIP3, E2F1, E2F2, E2F3, E2F4,
E2F5, E2F6, E2F7, E2F8, E4F1, EAF1, EAF2, EAPP, EARS2, EBAG9, EBF1, EBF2, EBF3,
EBF4, EBI3, EBLN1, EBLN2, EBNA1BP2, EBP, EBPL, ECD, ECE1, ECE2, ECEL1, ECH1,
ECHDC1, ECHDC2, ECHDC3, ECHS1, ECI1, ECI2, ECM1, ECM2, ECSCR, ECSIT, ECT2,
ECT2L, EDA, EDA2R, EDAR, EDARADD, EDC3, EDC4, EDDM13, EDDM3A, EDDM3B,
EDEM1, EDEM2, EDEM3, EDF1, EDIL3, EDN1, EDN2, EDN3, EDNRA, EDNRB, EDRF1,
EEA1, EED, EEF1A1, EEF1A2, EEF1AKMT1, EEF1AKMT2, EEF1AKMT3, EEF1B2, EEF1D,
EEF1E1, EEF1E1-BLOC1S5, EEF1G, EEF2, EEF2K, EEF2KMT, EEFSEC, EEPD1, EFCAB1,
EFCAB10, EFCAB11, EFCAB12, EFCAB13, EFCAB14, EFCAB2, EFCAB3, EFCAB5,
EFCAB6, EFCAB7, EFCAB8, EFCAB9, EFCC1, EFEMP1, EFEMP2, EFHB, EFHC1, EFHC2,
EFHD1, EFHD2, EFL1, EFNA1, EFNA2, EFNA3, EFNA4, EFNA5, EFNB1, EFNB2, EFNB3,
EFR3A, EFR3B, EFS, EFTUD2, EGF, EGFL6, EGFL7, EGFL8, EGFLAM, EGFR, EGLN1,
EGLN2, EGLN3, EGR1, EGR2, EGR3, EGR4, EHBP1, EHBP1L1, EHD1, EHD2, EHD3, EHD4,
EHF, EHHADH, EHMT1, EHMT2, EI24, EID1, EID2, EID2B, EID3, EIF1, EIFIAD, EIF1AX,
EIF1AY, EIF1B, EIF2A, EIF2AK1, EIF2AK2, EIF2AK3, EIF2AK4, EIF2B1, EIF2B2, EIF2B3,
EIF2B4, EIF2B5, EIF2D, EIF2S1, EIF2S2, EIF2S3, EIF3A, EIF3B, EIF3C, EIF3CL, EIF3D,
EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L, EIF3M, EIF4A1, EIF4A2, EIF4A3,
EIF4B, EIF4E, EIF4E1B, EIF4E2, EIF4E3, EIF4EBP1, EIF4EBP2, EIF4EBP3, EIF4ENIF1,
EIF4G1, EIF4G2, EIF4G3, EIF4H, EIF5, EIF5A, EIF5A2, EIF5AL1, EIF5B, EIF6, EIPR1,
ELAC1, ELAC2, ELANE, ELAVL1, ELAVL2, ELAVL3, ELAVL4, ELF1, ELF2, ELF3, ELF4,
ELF5, ELFN1, ELFN2, ELK1, ELK3, ELK4, ELL, ELL2, ELL3, ELMO1, ELMO2, ELMO3,
ELMOD1, ELMOD2, ELMOD3, ELMSAN1, ELN, ELOA, ELOA2, ELOA3, ELOA3B,
ELOA3C, ELOA3D, ELOB, ELOC, ELOF1, ELOVL1, ELOVL2, ELOVL3, ELOVL4,
ELOVL5, ELOVL6, ELOVL7, ELP1, ELP2, ELP3, ELP4, ELP5, ELP6, ELSPBP1, EMB, EMC1,
EMC10, EMC2, EMC3, EMC4, EMC6, EMC7, EMC8, EMC9, EMCN, EMD, EME1, EME2,
EMG1, EMID1, EMILIN1, EMILIN2, EMILIN3, EML1, EML2, EML3, EML4, EML5, EML6,
EMP1, EMP2, EMP3, EMSY, EMX1, EMX2, EN1, EN2, ENAH, ENAM, ENC1, ENDOD1,
ENDOG, ENDOU, ENDOV, ENG, ENGASE, ENHO, ENKD1, ENKUR, ENO1, ENO2, ENO3,
ENO4, ENOPH1, ENOSF1, ENOX1, ENOX2, ENPEP, ENPP1, ENPP2, ENPP3, ENPP4,
ENPP5, ENPP6, ENPP7, ENSA, ENTHD1, ENTPD1, ENTPD2, ENTPD3, ENTPD4, ENTPD5,
ENTPD6, ENTPD7, ENTPD8, ENY2, EOGT, EOMES, EP300, EP400, EPAS1, EPB41,
EPB41L1, EPB41L2, EPB41L3, EPB41L4A, EPB41L4B, EPB41L5, EPB42, EPC1, EPC2,
EPCAM, EPDR1, EPG5, EPGN, EPHA1, EPHA10, EPHA2, EPHA3, EPHA4, EPHA5, EPHA6,
EPHA7, EPHA8, EPHB1, EPHB2, EPHB3, EPHB4, EPHB6, EPHX1, EPHX2, EPHX3, EPHX4,
EPM2A, EPM2AIP1, EPN1, EPN2, EPN3, EPO, EPOP, EPOR, EPPIN, EPPIN-WFDC6, EPPK1,
EPRS, EPS15, EPS15L1, EPS8, EPS8L1, EPS8L2, EPS8L3, EPSTI1, EPX, EPYC, EQTN,
ERAL1, ERAP1, ERAP2, ERAS, ERBB2, ERBB3, ERBB4, ERBIN, ERC1, ERC2, ERCC1,
ERCC2, ERCC3, ERCC4, ERCC5, ERCC6, ERCC6L, ERCC6L2, ERCC8, EREG, ERF, ERFE,
ERG, ERG28, ERGIC1, ERGIC2, ERGIC3, ERH, ERI1, ERI2, ERI3, ERICH1, ERICH2,
ERICH3, ERICH4, ERICH5, ERICH6, ERICH6B, ERLEC1, ERLIN1, ERLIN2, ERMAP,
ERMARD, ERMN, ERMP1, ERN1, ERN2, ERO1A, ERO1B, ERP27, ERP29, ERP44, ERRFI1,
ERV3-1, ERVFRD-1, ERVMER34-1, ERVV-1, ERVV-2, ERVW-1, ESAM, ESCO1, ESCO2,
ESD, ESF1, ESM1, ESPL1, ESPN, ESPNL, ESR1, ESR2, ESRP1, ESRP2, ESRRA, ESRRB,
ESRRG, ESS2, ESX1, ESYT1, ESYT2, ESYT3, ETAA1, ETDA, ETDB, ETDC, ETF1, ETFA,
ETFB, ETFBKMT, ETFDH, ETFRF1, ETHE1, ETNK1, ETNK2, ETNPPL, ETS1, ETS2, ETV1,
ETV2, ETV3, ETV3L, ETV4, ETV5, ETV6, ETV7, EVA1A, EVA1B, EVA1C, EVC, EVC2,
EVI2A, EVI2B, EVI5, EVISL, EVL, EVPL, EVPLL, EVX1, EVX2, EWSR1, EXD1, EXD2,
EXD3, EXO1, EXO5, EXOC1, EXOC1L, EXOC2, EXOC3, EXOC3L1, EXOC3L2, EXOC3L4,
EXOC4, EXOC5, EXOC6, EXOC6B, EXOC7, EXOC8, EXOG, EXOSC1, EXOSC10, EXOSC2,
EXOSC3, EXOSC4, EXOSC5, EXOSC6, EXOSC7, EXOSC8, EXOSC9, EXPH5, EXT1, EXT2,
EXTL1, EXTL2, EXTL3, EYA1, EYA2, EYA3, EYA4, EYS, EZH1, EZH2, EZR, F10, F11,
F11R, F12, F13A1, F13B, F2, F2R, F2RL1, F2RL2, F2RL3, F3, F5, F7, F8, F8A1, F8A2, F8A3,
F9, FA2H, FAAH, FAAH2, FAAP100, FAAP20, FAAP24, FABP1, FABP12, FABP2, FABP3,
FABP4, FABP5, FABP6, FABP7, FABP9, FADD, FADS1, FADS2, FADS3, FADS6, FAF1,
FAF2, FAH, FAHD1, FAHD2A, FAHD2B, FAIM, FAIM2, FAM102A, FAM102B, FAM103A1,
FAM104A, FAM104B, FAM105A, FAM106A, FAM107A, FAM107B, FAM109A, FAM109B,
FAM110A, FAM110B, FAM110C, FAM110D, FAM111A, FAM111B, FAM114A1,
FAM114A2, FAM117A, FAM117B, FAM118A, FAM118B, FAM120A, FAM120AOS,
FAM120B, FAM120C, FAM122A, FAM122B, FAM122C, FAM124A, FAM124B, FAM126A,
FAM126B, FAM129A, FAM129B, FAM129C, FAM131A, FAM131B, FAM131C, FAM133A,
FAM133B, FAM135A, FAM135B, FAM136A, FAM13A, FAM13B, FAM13C, FAM149A,
FAM149B1, FAM151A, FAM151B, FAM153A, FAM153B, FAM153C, FAM155A, FAM155B,
FAM156A, FAM156B, FAM159A, FAM159B, FAM160A1, FAM160A2, FAM160B1,
FAM160B2, FAM161A, FAM161B, FAM162A, FAM162B, FAM163A, FAM163B, FAM166A,
FAM166B, FAM167A, FAM167B, FAM168A, FAM168B, FAM169A, FAM169B, FAM170A,
FAM170B, FAM171A1, FAM171A2, FAM171B, FAM172A, FAM173A, FAM173B,
FAM174A, FAM174B, FAM177A1, FAM177B, FAM178B, FAM180A, FAM180B, FAM181A,
FAM181B, FAM182B, FAM183A, FAM184A, FAM184B, FAM185A, FAM186A, FAM186B,
FAM187A, FAM187B, FAM189A1, FAM189A2, FAM189B, FAM192A, FAM193A,
FAM193B, FAM196A, FAM196B, FAM198A, FAM198B, FAM199X, FAM19A1, FAM19A2,
FAM19A3, FAM19A4, FAM19A5, FAM200A, FAM200B, FAM204A, FAM205A, FAM205C,
FAM206A, FAM207A, FAM208A, FAM208B, FAM209A, FAM209B, FAM20A, FAM20B,
FAM20C, FAM210A, FAM210B, FAM212A, FAM212B, FAM213A, FAM213B, FAM214A,
FAM214B, FAM216A, FAM216B, FAM217A, FAM217B, FAM218A, FAM219A, FAM219B,
FAM220A, FAM221A, FAM221B, FAM222A, FAM222B, FAM227A, FAM227B, FAM228A,
FAM228B, FAM229A, FAM229B, FAM230A, FAM231A, FAM231B, FAM231C, FAM231D,
FAM234A, FAM234B, FAM236A, FAM236B, FAM236C, FAM236D, FAM237A, FAM237B,
FAM240A, FAM240B, FAM24A, FAM24B, FAM25A, FAM25C, FAM25G, FAM26D,
FAM26E, FAM26F, FAM32A, FAM35A, FAM3A, FAM3B, FAM3C, FAM3D, FAM43A,
FAM43B, FAM45A, FAM46A, FAM46B, FAM46C, FAM46D, FAM47A, FAM47B, FAM47C,
FAM47E, FAM47E-STBD1, FAM49A, FAM49B, FAM50A, FAM50B, FAM53A, FAM53B,
FAM53C, FAM57A, FAM57B, FAM58A, FAM60A, FAM69A, FAM69B, FAM69C, FAM71A,
FAM71B, FAM71C, FAM71D, FAM71E1, FAM71E2, FAM71F1, FAM71F2, FAM72A,
FAM72B, FAM72C, FAM72D, FAM76A, FAM76B, FAM78A, FAM78B, FAM81A, FAM81B,
FAM83A, FAM83B, FAM83C, FAM83D, FAM83E, FAM83F, FAM83G, FAM83H, FAM84A,
FAM84B, FAM86B1, FAM86B2, FAM86C1, FAM89A, FAM89B, FAM8A1, FAM90A1,
FAM90A26, FAM91A1, FAM92A, FAM92B, FAM95C, FAM96A, FAM96B, FAM98A,
FAM98B, FAM98C, FAM9A, FAM9B, FAM9C, FAN1, FANCA, FANCB, FANCC, FANCD2,
FANCD2OS, FANCE, FANCF, FANCG, FANC1, FANCL, FANCM, FANK1, FAP, FAR1,
FAR2, FARP1, FARP2, FARS2, FARSA, FARSB, FAS, FASLG, FASN, FASTK, FASTKD1,
FASTKD2, FASTKD3, FASTKD5, FAT1, FAT2, FAT3, FAT4, FATE1, FAU, FAXC, FAXDC2,
FBF1, FBL, FBLIM1, FBLL1, FBLN1, FBLN2, FBLN5, FBLN7, FBN1, FBN2, FBN3, FBP1,
FBP2, FBRS, FBRSL1, FBXL12, FBXL13, FBXL14, FBXL15, FBXL16, FBXL17, FBXL18,
FBXL19, FBXL2, FBXL20, FBXL22, FBXL3, FBXL4, FBXL5, FBXL6, FBXL7, FBXL8,
FBXO10, FBXO11, FBXO15, FBXO16, FBXO17, FBXO18, FBXO2, FBXO21, FBXO22,
FBXO24, FBXO25, FBXO27, FBXO28, FBXO3, FBXO30, FBXO31, FBXO32, FBXO33,
FBXO34, FBXO36, FBXO38, FBXO39, FBXO4, FBXO40, FBXO41, FBXO42, FBXO43,
FBXO44, FBXO45, FBXO46, FBXO47, FBXO48, FBXO5, FBX06, FBXO7, FBX08, FBXO9,
FBXW10, FBXW11, FBXW12, FBXW2, FBXW4, FBXW5, FBXW7, FBXW8, FBXW9,
FCAMR, FCAR, FCERIA, FCER1G, FCER2, FCF1, FCGBP, FCGRIA, FCGRIB, FCGR2A,
FCGR2B, FCGR2C, FCGR3A, FCGR3B, FCGRT, FCHO1, FCHO2, FCHSD1, FCHSD2,
FCMR, FCN1, FCN2, FCN3, FCRL1, FCRL2, FCRL3, FCRL4, FCRL5, FCRL6, FCRLA,
FCRLB, FDCSP, FDFT1, FDPS, FDX1, FDX2, FDXACB1, FDXR, FECH, FEMIA, FEMIB,
FEMIC, FEN1, FER, FER1L5, FER1L6, FERD3L, FERMT1, FERMT2, FERMT3, FES,
FETUB, FEV, FEZ1, FEZ2, FEZF1, FEZF2, FFAR1, FFAR2, FFAR3, FFAR4, FGA, FGB,
FGD1, FGD2, FGD3, FGD4, FGD5, FGD6, FGF1, FGF10, FGF11, FGF12, FGF13, FGF14,
FGF16, FGF17, FGF18, FGF19, FGF2, FGF20, FGF21, FGF22, FGF23, FGF3, FGF4, FGF5,
FGF6, FGF7, FGF8, FGF9, FGFBP1, FGFBP2, FGFBP3, FGFR1, FGFR1OP, FGFR1OP2,
FGFR2, FGFR3, FGFR4, FGFRL1, FGG, FGGY, FGL1, FGL2, FGR, FH, FHAD1, FHDC1,
FHIT, FHL1, FHL2, FHL3, FHL5, FHOD1, FHOD3, FIBCD1, FIBIN, FIBP, FICD, FIG4,
FIGLA, FIGN, FIGNL1, FIGNL2, FILIP1, FILIP1L, FIP1L1 FIS1, FITM1, FITM2, FIZ1, FJX1,
FKBP10, FKBP11, FKBP14, FKBP15, FKBP1A, FKBP1B, FKBPIC, FKBP2, FKBP3, FKBP4,
FKBP5, FKBP6, FKBP7, FKBP8, FKBP9, FKBPL, FKRP, FKTN, FLAD1, FLCN, FLG, FLG2,
FLI1, FLI1, FLNA, FLNB, FLNC, FLOT1, FLOT2, FLRT1, FLRT2, FLRT3, FLT1, FLT3,
FLT3LG, FLT4, FLVCR1, FLVCR2, FLYWCH1, FLYWCH2, FMC1, FMN1, FMN2, FMNL1,
FMNL2, FMNL3, FMO1, FMO2, FMO3, FMO4, FMO5, FMOD, FMR1, FMR1NB, FN1, FN3K,
FN3KRP, FNBP1, FNBP1L, FNBP4, FNDC1, FNDC10, FNDC11, FNDC3A, FNDC3B, FNDC4,
FNDC5, FNDC7, FNDC8, FNDC9, FNIP1, FNIP2, FNTA, FNTB, FO681492.1, FO681542.1,
FOCAD, FOLH1, FOLR1, FOLR2, FOLR3, FOPNL, FOS, FOSB, FOSL1, FOSL2, FOXA1,
FOXA2, FOXA3, FOXB1, FOXB2, FOXC1, FOXC2, FOXD1, FOXD2, FOXD3, FOXD4,
FOXD4L1, FOXD4L3, FOXD4L4, FOXD4L5, FOXD4L6, FOXE1, FOXE3, FOXF1, FOXF2,
FOXG1, FOXH1, FOXI1, FOX12, FOXI3, FOXJ1, FOXJ2, FOXJ3, FOXK1, FOXK2, FOXL1,
FOXL2, FOXL2NB, FOXM1, FOXN1, FOXN2, FOXN3, FOXN4, FOXO1, FOXO3, FOXO4,
FOXO6, FOXP1, FOXP2, FOXP3, FOXP4, FOXQ1, FOXR1, FOXR2, FOXRED1, FOXRED2,
FOXS1, FP236240.1, FP565260.1, FP565260.2, FP565260.3, FP565260.4, FP565260.6,
FP565260.7, FP565324.1, FP565324.2, FPGS, FPGT, FPGT-TNNI3K, FPR1, FPR2, FPR3,
FRA10AC1, FRAS1, FRAT1, FRAT2, FREM1, FREM2, FREM3, FRG1, FRG2, FRG2B,
FRG2C, FRK, FRMD1, FRMD3, FRMD4A, FRMD4B, FRMD5, FRMD6, FRMD7, FRMD8,
FRMPD1, FRMPD2, FRMPD3, FRMPD4, FRRS1, FRRS1L, FRS2, FRS3, FRY, FRYL, FRZB,
FSBP, FSCB, FSCN1, FSCN2, FSCN3, FSD1, FSD1L, FSD2, FSHB, FSHR, FSIP1, FSIP2, FST,
FSTL1, FSTL3, FSTL4, FSTL5, FTCD, FTCDNL1, FTH1, FTHL17, FTL, FTMT, FTO, FTSJ1,
FTSJ3, FUBP1, FUBP3, FUCA1, FUCA2, f*ck, FUNDC1, FUNDC2, FUOM, FURIN, FUS,
FUT1, FUT10, FUT11, FUT2, FUT3, FUT4, FUT5, FUT6, FUT7, FUT8, FUT9, FUZ, FXN,
FXR1, FXR2, FXYD1, FXYD2, FXYD3, FXYD4, FXYD5, FXYD6, FXYD6-FXYD2, FXYD7,
FYB1, FYB2, FYCO1, FYN, FYTTD1, FZD1, FZD10, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7,
FZD8, FZD9, FZR1, GOS2, G2E3, G3BP1, G3BP2, G6PC, G6PC2, G6PC3, G6PD, GAA, GAB1,
GAB2, GAB3, GAB4, GABARAP, GABARAPL1, GABARAPL2, GABBR1, GABBR2,
GABPA, GABPB1, GABPB2, GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6,
GABRB1, GABRB2, GABRB3, GABRD, GABRE, GABRG1, GABRG2, GABRG3, GABRP,
GABRQ, GABRR1, GABRR2, GABRR3, GAD1, GAD2, GADD45A, GADD45B, GADD45G,
GADD45GIP1, GADL1, GAGE1, GAGE10, GAGE12B, GAGE12C, GAGE12D, GAGE12E,
GAGE12F, GAGE12G, GAGE12H, GAGE12J, GAGE13, GAGE2A, GAGE2E, GAK, GAL,
GAL3ST1, GAL3ST2, GAL3ST3, GAL3ST4, GALC, GALE, GALK1, GALK2, GALM,
GALNS, GALNT1, GALNT10, GALNT11, GALNT12, GALNT13, GALNT14, GALNT15,
GALNT16, GALNT17, GALNT18, GALNT2, GALNT3, GALNT4, GALNT5, GALNT6,
GALNT7, GALNT8, GALNT9, GALNTL5, GALNTL6, GALP, GALR1, GALR2, GALR3,
GALT, GAMT, GAN, GANAB, GANC, GAP43, GAPDH, GAPDHS, GAPT, GAPVD1, GAR1,
GAREM1, GAREM2, GARNL3, GARS, GART, GAS1, GAS2, GAS2L1, GAS2L2, GAS2L3,
GAS6, GAS7, GAS8, GAST, GATA1, GATA2, GATA3, GATA4, GATA5, GATA6, GATAD1,
GATAD2A, GATAD2B, GATB, GATC, GATD1, GATM, GATS, GBA, GBA2, GBA3, GBE1,
GBF1, GBGT1, GBP1, GBP2, GBP3, GBP4, GBP5, GBP6, GBP7, GBX1, GBX2, GC, GCA,
GCAT, GCC1, GCC2, GCDH, GCFC2, GCG, GCGR, GCH1, GCHFR, GCK, GCKR, GCLC,
GCLM, GCM1, GCM2, GCN1, GCNA, GCNT1, GCNT2, GCNT3, GCNT4, GCNT7, GCOM1,
GCSAM, GCSAML, GCSH, GDA, GDAP1, GDAP1L1, GDAP2, GDE1, GDF1, GDF10,
GDF11, GDF15, GDF2, GDF3, GDF5, GDF5OS, GDF6, GDF7, GDF9, GDI1, GDI2, GDNF,
GDPD1, GDPD2, GDPD3, GDPD4, GDPD5, GDPGP1, GEM, GEMIN2, GEMIN4, GEMIN5,
GEMIN6, GEMIN7, GEMIN8, GEN1, GET4, GFAP, GFER, GFI1, GFIIB, GFM1, GFM2,
GFOD1, GFOD2, GFPT1, GFPT2, GFRA1, GFRA2, GFRA3, GFRA4, GFRAL, GFY, GGA1,
GGA2, GGA3, GGACT, GGCT, GGCX, GGH, GGN, GGNBP2, GGPS1, GGT1, GGT2, GGT5,
GGT6, GGT7, GGTLC1, GGTLC2, GGTLC3, GH1, GH2, GHDC, GHITM, GHR, GHRH,
GHRHR, GHRL, GHSR, GID4, GID8, GIF, GIGYF1, GIGYF2, GIMAP1, GIMAP1-GIMAP5,
GIMAP2, GIMAP4, GIMAP5, GIMAP6, GIMAP7, GIMAP8, GIMD1, GIN1, GINM1, GINS1,
GINS2, GINS3, GINS4, GIP, GIPC1, GIPC2, GIPC3, GIPR, GIT1, GIT2, GJA1, GJA10, GJA3,
GJA4, GJA5, GJA8, GJA9, GJB1, GJB2, GJB3, GJB4, GJB5, GJB6, GJB7, GJC1, GJC2, GJC3,
GJD2, GJD3, GJD4, GJE1, GK, GK2, GK3P, GK5, GKAP1, GKN1, GKN2, GLA, GLB1,
GLB1L, GLB1L2, GLB1L3, GLCCI1, GLCE, GLDC, GLDN, GLE1, GLG1, GLI1, GLI2, GLI3,
GLI4, GLIPR1, GLIPR1L1, GLIPR1L2, GLIPR2, GLIS1, GLIS2, GLIS3, GLMN, GLMP,
GLO1, GLOD4, GLOD5, GLPIR, GLP2R, GLRA1, GLRA2, GLRA3, GLRA4, GLRB, GLRX,
GLRX2, GLRX3, GLRX5, GLS, GLS2, GLTID1, GLT6D1, GLT8D1, GLT8D2, GLTP,
GLTPD2, GLUD1, GLUD2, GLUL, GLYAT, GLYATL1, GLYATLIP3, GLYATL2,
GLYATL3, GLYCTK, GLYR1, GM2A, GMCL1, GMDS, GMEB1, GMEB2, GMFB, GMFG,
GMIP, GML, GMNC, GMNN, GMPPA, GMPPB, GMPR, GMPR2, GMPS, GNA11, GNA12,
GNA13, GNA14, GNA15, GNAI1, GNAI2, GNAI3, GNAL, GNAO1, GNAQ, GNAS, GNAT1,
GNAT2, GNAT3, GNAZ, GNB1, GNB1L, GNB2, GNB3, GNB4, GNB5, GNE, GNG10,
GNG11, GNG12, GNG13, GNG14, GNG2, GNG3, GNG4, GNG5, GNG7, GNG8, GNGT1,
GNGT2, GNL1, GNL2, GNL3, GNL3L, GNLY, GNMT, GNPAT, GNPDA1, GNPDA2,
GNPNAT1, GNPTAB, GNPTG, GNRH1, GNRH2, GNRHR, GNS, GOLGA1, GOLGA2,
GOLGA3, GOLGA4, GOLGA5, GOLGA6A, GOLGA6B, GOLGA6C, GOLGA6D,
GOLGA6L1, GOLGA6L10, GOLGA6L2, GOLGA6L22, GOLGA6L4, GOLGA6L6,
GOLGA6L7P, GOLGA6L9, GOLGA7, GOLGA7B, GOLGA8A, GOLGA8B, GOLGA8F,
GOLGA8G, GOLGA8H, GOLGA8J, GOLGA8K, GOLGA8M, GOLGA8N, GOLGA80,
GOLGA8Q, GOLGA8R, GOLGA8S, GOLGAST, GOLGB1, GOLIM4, GOLM1, GOLPH3,
GOLPH3L, GOLTIA, GOLTIB, GON4L, GON7, GOPC, GORAB, GORASP1, GORASP2,
GOSR1, GOSR2, GOT1, GOT1L1, GOT2, GPIBA, GPIBB, GP2, GP5, GP6, GP9, GPA33,
GPAA1, GPALPP1, GPAM, GPANK1, GPAT2, GPAT3, GPAT4, GPATCH1, GPATCH11,
GPATCH2, GPATCH2L, GPATCH3, GPATCH4, GPATCH8, GPBAR1, GPBP1, GPBP1L1,
GPC1, GPC2, GPC3, GPC4, GPC5, GPC6, GPCPD1, GPD1, GPD1L, GPD2, GPER1, GPHA2,
GPHB5, GPHN, GPI, GPIHBP1, GPKOW, GPLD1, GPM6A, GPM6B, GPN1, GPN2, GPN3,
GPNMB, GPR1, GPR101, GPR107, GPR108, GPR119, GPR12, GPR132, GPR135, GPR137,
GPR137B, GPR137C, GPR139, GPR141, GPR142, GPR143, GPR146, GPR148, GPR149,
GPR15, GPR150, GPR151, GPR152, GPR153, GPR155, GPR156, GPR157, GPR158, GPR160,
GPR161, GPR162, GPR17, GPR171, GPR173, GPR174, GPR176, GPR179, GPR18, GPR180,
GPR182, GPR183, GPR19, GPR20, GPR21, GPR22, GPR25, GPR26, GPR27, GPR3, GPR31,
GPR32, GPR33, GPR34, GPR35, GPR37, GPR37L1, GPR39, GPR4, GPR42, GPR45, GPR50,
GPR52, GPR55, GPR6, GPR61, GPR62, GPR63, GPR65, GPR68, GPR75, GPR75-ASB3,
GPR78, GPR82, GPR83, GPR84, GPR85, GPR87, GPR88, GPR89A, GPR89B, GPRASP1,
GPRASP2, GPRC5A, GPRC5B, GPRC5C, GPRC5D, GPRC6A, GPRIN1, GPRIN2, GPRIN3,
GPS1, GPS2, GPSM1, GPSM2, GPSM3, GPT, GPT2, GPX1, GPX2, GPX3, GPX4, GPX5,
GPX6, GPX7, GPX8, GRAMDIA, GRAMDIB, GRAMDIC, GRAMD2A, GRAMD2B,
GRAMD4, GRAP, GRAP2, GRAPL, GRASP, GRB10, GRB14, GRB2, GRB7, GREB1,
GREB1L, GREM1, GREM2, GRHL1, GRHL2, GRHL3, GRHPR, GRIA1, GRIA2, GRIA3,
GRIA4, GRID1, GRID2, GRID2IP, GRIFIN, GRIK1, GRIK2, GRIK3, GRIK4, GRIK5, GRIN1,
GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRIN3A, GRIN3B, GRINA, GRIP1, GRIP2, GRIPAP1,
GRK1, GRK2, GRK3, GRK4, GRK5, GRK6, GRK7, GRM1, GRM2, GRM3, GRM4, GRM5,
GRM6, GRM7, GRM8, GRN, GRP, GRPEL1, GRPEL2, GRPR, GRSF1, GRTP1, GRWD1,
GRXCR1, GRXCR2, GSAP, GSC, GSC2, GSDMA, GSDMB, GSDMC, GSDMD, GSE1, GSG1,
GSG1L, GSG1L2, GSK3A, GSK3B, GSKIP, GSN, GSPT1, GSPT2, GSR, GSS, GSTA1, GSTA2,
GSTA3, GSTA4, GSTA5, GSTCD, GSTK1, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5,
GSTO1, GSTO2, GSTP1, GSTT1, GSTT2, GSTT2B, GSTTP1, GSTZ1, GSX1, GSX2, GTDC1,
GTF2A1, GTF2A1L, GTF2A2, GTF2B, GTF2E1, GTF2E2, GTF2F1, GTF2F2, GTF2H1,
GTF2H2, GTF2H2C, GTF2H2C_2, GTF2H3, GTF2H4, GTF2H5, GTF2I, GTF2IRD1,
GTF2IRD2, GTF2IRD2B, GTF3A, GTF3C1, GTF3C2, GTF3C3, GTF3C4, GTF3C5, GTF3C6,
GTPBP1, GTPBP10, GTPBP2, GTPBP3, GTPBP4, GTPBP6, GTPBP8, GTSE1, GTSF1,
GTSF1L, GU182339.1, GU182339.3, GU182343.1, GU182343.2, GU182345.1, GU182345.2,
GU182347.1, GU182351.2, GU182352.2, GU182353.1, GU182355.1, GU182355.2,
GU182355.3, GU182357.1, GU182357.3, GU182359.1, GU182359.2, GUCAIA, GUCAIB,
GUCA1C, GUCA2A, GUCA2B, GUCD1, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C,
GUCY2D, GUCY2F, GUF1, GUK1, GULP1, GUSB, GVQW2, GXYLT1, GXYLT2, GYG1,
GYG2, GYPA, GYPB, GYPC, GYPE, GYS1, GYS2, GZF1, GZMA, GZMB, GZMH, GZMK,
GZMM, H1F0, HIFNT, HIFOO, HIFX, H2AFB1, H2AFB2, H2AFB3, H2AFJ, H2AFV,
H2AFX, H2AFY, H2AFY2, H2AFZ, H2BFM, H2BFS, H2BFWT, H3F3A, H3F3B, H3F3C,
H6PD, HAAO, HABP2, HABP4, HACD1, HACD2, HACD3, HACD4, HACE1, HACL1,
HADH, HADHA, HADHB, HAGH, HAGHL, HAL, HAMP, HAND1, HAND2, HAO1, HAO2,
HAP1, HAPLN1, HAPLN2, HAPLN3, HAPLN4, HARBI1, HARS, HARS2, HAS1, HAS2,
HAS3, HASPIN, HAT1, HAUS1, HAUS2, HAUS3, HAUS4, HAUS5, HAUS6, HAUS7,
HAUS8, HAVCR1, HAVCR2, HAX1, HBA1, HBA2, HBB, HBD, HBE1, HBEGF, HBG1,
HBG2, HBM, HBP1, HBQ1, HBS1L, HBZ, HCAR1, HCAR2, HCAR3, HCCS, HCFC1,
HCFC1R1, HCFC2, HCK, HCLS1, HCN1, HCN2, HCN3, HCN4, HCRT, HCRTR1, HCRTR2,
HCST, HDAC1, HDAC10, HDAC11, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7,
HDAC8, HDAC9, HDC, HDDC2, HDDC3, HDGF, HDGFL1, HDGFL2, HDGFL3, HDHD2,
HDHD3, HDHD5, HDLBP, HDX, HEATR1, HEATR3, HEATR4, HEATRSA, HEATR5B,
HEATR6, HEATR9, HEBP1, HEBP2, HECA, HECTD1, HECTD2, HECTD3, HECTD4,
HECW1, HECW2, HEG1, HELB, HELLS, HELQ, HELT, HELZ, HELZ2, HEMGN, HEMK1,
HENMT1, HEPACAM, HEPACAM2, HEPH, HEPHL1, HEPN1, HERC1, HERC2, HERC3,
HERC4, HERC5, HERC6, HERPUD1, HERPUD2, HES1, HES2, HES3, HES4, HES5, HES6,
HES7, HESX1, HEXA, HEXB, HEXDC, HEXIM1, HEXIM2, HEY1, HEY2, HEYL, HFE,
HFE2, HFM1, HGD, HGF, HGFAC, HGH1, HGNC:18790, HGNC:24955, HGS, HGSNAT,
HHAT, HHATL, HHEX, HHIP, HHIPL1, HHIPL2, HHLA1, HHLA2, HHLA3, HIBADH,
HIBCH, HIC1, HIC2, HID1, HIFIA, HIFIAN, HIF3A, HIGDIA, HIGDIB, HIGDIC, HIGD2A,
HIGD2B, HIKESH1, HILPDA, HINFP, HINT1, HINT2, HINT3, HIP1, HIPIR, HIPK1, HIPK2,
HIPK3, HIPK4, HIRA, HIRIP3, HISTIHIA, HISTIHIB, HISTIHIC, HISTIHID, HISTIHIE,
HISTIHIT, HIST1H2AA, HISTIH2AB, HIST1H2AC, HIST1H2AD, HIST1H2AE,
HIST1H2AG, HIST1H2AH, HIST1H2AI, HIST1H2AJ, HIST1H2AK, HIST1H2AL,
HIST1H2AM, HIST1H2BA, HIST1H2BB, HIST1H2BC, HIST1H2BD, HIST1H2BE,
HIST1H2BF, HIST1H2BG, HIST1H2BH, HIST1H2BI, HIST1H2BJ, HIST1H2BK,
HIST1H2BL, HIST1H2BM, HIST1H2BN, HIST1H2BO, HIST1H3A, HIST1H3B, HIST1H3C,
HIST1H3D, HIST1H3E, HIST1H3F, HIST1H3G, HIST1H3H, HIST1H3I, HIST1H3J,
HIST1H4A, HIST1H4B, HISTIH4C, HIST1H4D, HIST1H4E, HIST1H4F, HIST1H4G,
HIST1H4H, HIST1H4I, HIST1H4J, HIST1H4K, HIST1H4L, HIST2H2AA3, HIST2H2AA4,
HIST2H2AB, HIST2H2AC, HIST2H2BE, HIST2H2BF, HIST2H3A, HIST2H3C, HIST2H3D,
HIST2H3PS2, HIST2H4A, HIST2H4B, HIST3H2A, HIST3H2BB, HIST3H3, HIST4H4,
HIVEP1, HIVEP2, HIVEP3, HJURP, HK1, HK2, HK3, HKDC1, HKR1, HLA-A, HLA-B, HLA-
C, HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DPA1, HLA-DPB1, HLA-DQA1,
HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4,
HLA-DRB5, HLA-E, HLA-F, HLA-G, HLCS, HLF, HLTF, HLX, HM13, HM190170.1,
HMBOX1, HMBS, HMCES, HMCN1, HMCN2, HMG20A, HMG20B, HMGA1, HMGA2,
HMGB1, HMGB2, HMGB3, HMGB4, HMGCL, HMGCLL1, HMGCR, HMGCS1, HMGCS2,
HMGN1, HMGN2, HMGN3, HMGN4, HMGN5, HMGXB3, HMGXB4, HMHB1, HMMR,
HMOX1, HMOX2, HMSD, HMX1, HMX2, HMX3, HNF1A, HNF1B, HNF4A, HNF4G, HNMT,
HNRNPA0, HNRNPA1, HNRNPA1L2, HNRNPA2B1, HNRNPA3, HNRNPAB, HNRNPC,
HNRNPCL1, HNRNPCL2, HNRNPCL3, HNRNPCL4, HNRNPD, HNRNPDL, HNRNPF,
HNRNPH1, HNRNPH2, HNRNPH3, HNRNPK, HNRNPL, HNRNPLL, HNRNPM, HNRNPR,
HNRNPU, HNRNPUL1, HNRNPUL2, HNRNPUL2-BSCL2, HOGA1, HOMER1, HOMER2,
HOMER3, HOMEZ, HOOK1, HOOK2, HOOK3, HOPX, HORMAD1, HORMAD2, HOXA1,
HOXA10, HOXA11, HOXA13, HOXA2, HOXA3, HOXA4, HOXA5, HOXA6, HOXA7,
HOXA9, HOXB1, HOXB13, HOXB2, HOXB3, HOXB4, HOXB5, HOXB6, HOXB7, HOXB8,
HOXB9, HOXC10, HOXC11, HOXC12, HOXC13, HOXC4, HOXC5, HOXC6, HOXC8,
HOXC9, HOXD1, HOXD10, HOXD11, HOXD12, HOXD13, HOXD3, HOXD4, HOXD8,
HOXD9, HP, HP1BP3, HPCA, HPCAL1, HPCAL4, HPD, HPDL, HPF1, HPGD, HPGDS, HPN,
HPR, HPRT1, HPS1, HPS3, HPS4, HPS5, HPS6, HPSE, HPSE2, HPX, HR, HRAS, HRASLS,
HRASLS2, HRASLS5, HRC, HRCT1, HRG, HRH1, HRH2, HRH3, HRH4, HRK, HRNR,
HS1BP3, HS2ST1, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, HS3ST4, HS3ST5, HS3ST6,
HS6ST1, HS6ST2, HS6ST3, HSBP1, HSBP1L1, HSCB, HSD11B1, HSD11B1L, HSD11B2,
HSD17B1, HSD17B10, HSD17B11, HSD17B12, HSD17B13, HSD17B14, HSD17B2,
HSD17B3, HSD17B4, HSD17B6, HSD17B7, HSD17B8, HSD3B1, HSD3B2, HSD3B7, HSDL1,
HSDL2, HSF1, HSF2, HSF2BP, HSF4, HSF5, HSFX1, HSFX2, HSFX3, HSFX4, HSFY1,
HSFY2, HSH2D, HSP90AA1, HSP90AB1, HSP90B1, HSPA12A, HSPA12B, HSPA13,
HSPA14, HSPA1A, HSPA1B, HSPA1L, HSPA2, HSPA4, HSPA4L, HSPA5, HSPA6, HSPA8,
HSPA9, HSPB1, HSPB11, HSPB2, HSPB2-C11orf52, HSPB3, HSPB6, HSPB7, HSPB8, HSPB9,
HSPBAP1, HSPBP1, HSPD1, HSPE1, HSPE1-MOB4, HSPG2, HSPH1, HTATIP2, HTATSF1,
HTD2, HTN1, HTN3, HTRIA, HTRIB, HTRID, HTRIE, HTRIF, HTR2A, HTR2B, HTR2C,
HTR3A, HTR3B, HTR3C, HTR3D, HTR3E, HTR4, HTR5A, HTR6, HTR7, HTRA1, HTRA2,
HTRA3, HTRA4, HTT, HUNK, HUS1, HUS1B, HUWE1, HVCN1, HYAL1, HYAL2, HYAL3,
HYAL4, HYDIN, HYI, HYKK, HYLS1, HYOU1, HYPK, HYPM, IAH1, IAPP, IARS, IARS2,
IBA57, IBSP, IBTK, ICA1, ICA1L, ICAM1, ICAM2, ICAM3, ICAM4, ICAM5, ICE1, ICE2,
ICK, ICMT, ICOS, ICOSLG, ID1, ID2, ID3, ID4, IDE, IDH1, IDH2, IDH3A, IDH3B, IDH3G,
IDI1, IDI2, IDNK, IDO1, IDO2, IDS, IDUA, IER2, IER3, IER3IP1, IER5, IER5L, IFFO1, IFFO2,
IFI16, IFI27, IFI27L1, IFI27L2, IFI30, IFI35, IFI44, IFI44L, IFI6, IFIH1, IFIT1, IFITIB, IFIT2,
IFIT3, IFIT5, IFITM1, IFITM10, IFITM2, IFITM3, IFITM5, IFNA1, IFNA10, IFNA13, IFNA14,
IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2,
IFNB1, IFNE, IFNG, IFNGR1, IFNGR2, IFNK, IFNL1, IFNL2, IFNL3, IFNL4, IFNLR1,
IFNW1, IFRD1, IFRD2, IFT122, IFT140, IFT172, IFT20, IFT22, IFT27, IFT43, IFT46, IFT52,
IFT57, IFT74, IFT80, IFT81, IFT88, IGBP1, IGDCC3, IGDCC4, IGF1, IGFIR, IGF2, IGF2BP1,
IGF2BP2, IGF2BP3, IGF2R, IGFALS, IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, IGFBP6,
IGFBP7, IGFBPL1, IGFL1, IGFL2, IGFL3, IGFL4, IGFLR1, IGFN1, IGHA1, IGHA2, IGHD,
IGHD1-1, IGHD1-14, IGHD1-20, IGHD1-26, IGHD1-7, IGHD1OR15-1A, IGHD1OR15-1B,
IGHD2-15, IGHD2-2, IGHD2-21, IGHD2-8, IGHD2OR15-2A, IGHD2OR15-2B, IGHD3-10,
IGHD3-16, IGHD3-22, IGHD3-3, IGHD3-9, IGHD3OR15-3A, IGHD3OR15-3B, IGHD4-11,
IGHD4-17, IGHD4-23, IGHD4-4, IGHD4OR15-4A, IGHD4OR15-4B, IGHD5-12, IGHD5-18,
IGHD5-24, IGHD5-5, IGHD5OR15-5A, IGHD5OR15-5B, IGHD6-13, IGHD6-19, IGHD6-25,
IGHD6-6, IGHD7-27, IGHE, IGHG1, IGHG2, IGHG3, IGHG4, IGHJ1, IGHJ2, IGHJ3, IGHJ4,
IGHJ5, IGHJ6, IGHM, IGHMBP2, IGHV1-18, IGHV1-2, IGHV1-24, IGHV1-3, IGHV1-45,
IGHV1-46, IGHV1-58, IGHV1-69, IGHVIOR15-1, IGHV1OR15-9, IGHV1OR21-1, IGHV2-26,
IGHV2-5, IGHV2-70, IGHV2OR16-5, IGHV3-11, IGHV3-13, IGHV3-15, IGHV3-16, IGHV3-
20, IGHV3-21, IGHV3-23, IGHV3-30, IGHV3-33, IGHV3-35, IGHV3-38, IGHV3-43, IGHV3-
48, IGHV3-49, IGHV3-53, IGHV3-64, IGHV3-66, IGHV3-7, IGHV3-72, IGHV3-73, IGHV3-74,
IGHV3OR15-7, IGHV3OR16-10, IGHV3OR16-12, IGHV3OR16-13, IGHV3OR16-8,
IGHV3OR16-9, IGHV4-28, IGHV4-31, IGHV4-34, IGHV4-39, IGHV4-4, IGHV4-59, IGHV4-
61, IGHV4OR15-8, IGHV5-51, IGHV6-1, IGHV7-81, IGIP, IGKC, IGKJ1, IGKJ2, IGKJ3,
IGKJ4, IGKJ5, IGKV1-12, IGKV1-16, IGKV1-17, IGKV1-27, IGKV1-33, IGKV1-37, IGKV1-
39, IGKV1-5, IGKV1-6, IGKV1-8, IGKV1-9, IGKVID-12, IGKVID-13, IGKVID-16,
IGKVID-17, IGKVID-33, IGKVID-37, IGKVID-39, IGKVID-42, IGKVID-43, IGKVID-8,
IGKV1OR2-108, IGKV2-24, IGKV2-28, IGKV2-30, IGKV2-40, IGKV2D-24, IGKV2D-26,
IGKV2D-28, IGKV2D-29, IGKV2D-30, IGKV2D-40, IGKV3-11, IGKV3-15, IGKV3-20,
IGKV3-7, IGKV3D-11, IGKV3D-15, IGKV3D-20, IGKV3D-7, IGKV3OR2-268, IGKV4-1,
IGKV5-2, IGKV6-21, IGKV6D-21, IGKV6D-41, IGLC1, IGLC2, IGLC3, IGLC7, IGLJ1, IGLJ2,
IGLJ3, IGLJ4, IGLJ5, IGLJ6, IGLJ7, IGLL1, IGLL5, IGLON5, IGLV10-54, IGLV11-55, IGLV1-
36, IGLV1-40, IGLV1-44, IGLV1-47, IGLV1-50, IGLV1-51, IGLV2-11, IGLV2-14, IGLV2-18,
IGLV2-23, IGLV2-33, IGLV2-8, IGLV3-1, IGLV3-10, IGLV3-12, IGLV3-16, IGLV3-19,
IGLV3-21, IGLV3-22, IGLV3-25, IGLV3-27, IGLV3-32, IGLV3-9, IGLV4-3, IGLV4-60,
IGLV4-69, IGLV5-37, IGLV5-45, IGLV5-48, IGLV5-52, IGLV6-57, IGLV7-43, IGLV7-46,
IGLV8-61, IGLV9-49, IGSF1, IGSF10, IGSF11, IGSF21, IGSF22, IGSF23, IGSF3, IGSF5,
IGSF6, IGSF8, IGSF9, IGSF9B, IHH, IK, IKBIP, IKBKB, IKBKE, IKBKG, IKZF1, IKZF2,
IKZF3, IKZF4, IKZF5, IL10, IL1ORA, ILIORB, IL11, IL11RA, IL12A, IL12B, IL12RB1,
IL12RB2, IL13, IL13RA1, IL13RA2, IL15, IL15RA, IL16, IL17A, IL17B, IL17C, IL17D, IL17F,
IL17RA, IL17RB, IL17RC, IL17RD, IL17RE, IL17REL, IL18, IL18BP, IL18R1, IL18RAP, IL19,
IL1A, IL1B, IL1F10, IL1R1, IL1R2, IL1RAP, IL1RAPL1, IL1RAPL2, IL1RL1, IL1RL2, IL1RN,
IL2, IL20, IL20RA, IL20RB, IL21, IL21R, IL22, IL22RA1, IL22RA2, IL23A, IL23R, IL24, IL25,
IL26, IL27, IL27RA, IL2RA, IL2RB, IL2RG, IL3, IL31, IL31RA, IL32, IL33, IL34, IL36A,
IL36B, IL36G, IL36RN, IL37, IL3RA, IL4, IL411, IL4R, IL5, IL5RA, IL6, IL6R, IL6ST, IL7,
IL7R, IL9, IL9R, ILDR1, ILDR2, ILF2, ILF3, ILK, ILKAP, ILVBL, IMMP1L, IMMP2L, IMMT,
IMP3, IMP4, IMPA1, IMPA2, IMPACT, IMPAD1, IMPDH1, IMPDH2, IMPG1, IMPG2, INA,
INAFM1, INAFM2, INAVA, INCA1, INCENP, INF2, ING1, ING2, ING3, ING4, ING5, INHA,
INHBA, INHBB, INHBC, INHBE, INIP, INMT, INMT-MINDY4, INO80, INO80B, INO80B-
WBP1, INO80C, INO80D, INO80E, INPP1, INPP4A, INPP4B, INPP5A, INPP5B, INPP5D,
INPP5E, INPP5F, INPP5J, INPP5K, INPPL1, INS, INSC, INSIG1, INSIG2, INS-IGF2, INSL3,
INSL4, INSL5, INSL6, INSM1, INSM2, INSR, INSRR, INTS1, INTS10, INTS11, INTS12,
INTS13, INTS14, INTS2, INTS3, INTS4, INTS5, INTS6, INTS6L, INTS7, INTS8, INTS9,
INTU, INVS, IP6K1, IP6K2, IP6K3, IPCEF1, IPMK, IPO11, IPO13, IPO4, IPO5, IPO7, IPO8,
IPO9, IPP, IPPK, IQANK1, IQCA1, IQCA1L, IQCB1, IQCC, IQCD, IQCE, IQCF1, IQCF2,
IQCF3, IQCF5, IQCF6, IQCG, IQCH, IQCJ, IQCJ-SCHIP1, IQCK, IQCM, IQGAP1, IQGAP2,
IQGAP3, IQSEC1, IQSEC2, IQSEC3, IQUB, IREB2, IRF1, IRF2, IRF2BP1, IRF2BP2,
IRF2BPL, IRF3, IRF4, IRF5, IRF6, IRF7, IRF8, IRF9, IRGC, IRGM, IRGQ, IRS1, IRS2, IRS4,
IRX1, IRX2, IRX3, IRX4, IRX5, IRX6, ISCA1, ISCA2, ISCU, ISG15, ISG20, ISG20L2, ISL1,
ISL2, ISLR, ISLR2, ISM1, ISM2, ISOC1, ISOC2, ISPD, IST1, ISX, ISY1, ISY1-RAB43,
ISYNA1, ITCH, ITFG1, ITFG2, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4,
ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGAX,
ITGB1, ITGB1BP1, ITGB1BP2, ITGB2, ITGB3, ITGB3BP, ITGB4, ITGB5, ITGB6, ITGB7,
ITGB8, ITGBL1, ITIH1, ITIH2, ITIH3, ITIH4, ITIH5, ITIH6, ITK, ITLN1, ITLN2, ITM2A,
ITM2B, ITM2C, ITPA, ITPK1, ITPKA, ITPKB, ITPKC, ITPR1, ITPR2, ITPR3, ITPRIP,
ITPRIPL1, ITPRIPL2, ITSN1, ITSN2, IVD, IVL, IVNS1ABP, IWS1, IYD, IZUMO1, IZUMO1R,
IZUMO2, IZUMO3, IZUMO4, JADE1, JADE2, JADE3, JAG1, JAG2, JAGN1, JAK1, JAK2,
JAK3, JAKMIP1, JAKMIP2, JAKMIP3, JAM2, JAM3, JAML, JARID2, JAZF1, JCAD,
JCHAIN, JDP2, JKAMP, JMJD1C, JMJD4, JMJD6, JMJD7, JMJD7-PLA2G4B, JMJD8, JMY,
JOSD1, JOSD2, JPH1, JPH2, JPH3, JPH4, JPT1, JPT2, JRK, JRKL, JSRP1, JTB, JUN, JUNB,
JUND, JUP, KAAG1, KALRN, KANK1, KANK2, KANK3, KANK4, KANSL1, KANSL1L,
KANSL2, KANSL3, KANTR, KARS, KAT14, KAT2A, KAT2B, KAT5, KAT6A, KAT6B,
KAT7, KAT8, KATNA1, KATNAL1, KATNAL2, KATNB1, KATNBL1, KAZALD1, KAZN,
KBTBD11, KBTBD11-OT1, KBTBD12, KBTBD13, KBTBD2, KBTBD3, KBTBD4, KBTBD6,
KBTBD7, KBTBD8, KCMF1, KCNA1, KCNA10, KCNA2, KCNA3, KCNA4, KCNA5,
KCNA7, KCNAB1, KCNAB2, KCNAB3, KCNB1, KCNB2, KCNC1, KCNC2, KCNC3,
KCNC4, KCND1, KCND2, KCND3, KCNE1, KCNE1B, KCNE2, KCNE3, KCNE4, KCNE5,
KCNF1, KCNG1, KCNG2, KCNG3, KCNG4, KCNH1, KCNH2, KCNH3, KCNH4, KCNH5,
KCNH6, KCNH7, KCNH8, KCNIP1, KCNIP2, KCNIP3, KCNIP4, KCNJ1, KCNJ10, KCNJ11,
KCNJ12, KCNJ13, KCNJ14, KCNJ15, KCNJ16, KCNJ18, KCNJ2, KCNJ3, KCNJ4, KCNJ5,
KCNJ6, KCNJ8, KCNJ9, KCNK1, KCNK10, KCNK12, KCNK13, KCNK15, KCNK16,
KCNK17, KCNK18, KCNK2, KCNK3, KCNK4, KCNK5, KCNK6, KCNK7, KCNK9,
KCNMA1, KCNMB1, KCNMB2, KCNMB3, KCNMB4, KCNN1, KCNN2, KCNN3, KCNN4,
KCNQ1, KCNQ2, KCNQ3, KCNQ4, KCNQ5, KCNRG, KCNS1, KCNS2, KCNS3, KCNT1,
KCNT2, KCNU1, KCNV1, KCNV2, KCP, KCTD1, KCTD10, KCTD11, KCTD12, KCTD13,
KCTD14, KCTD15, KCTD16, KCTD17, KCTD18, KCTD19, KCTD2, KCTD20, KCTD21,
KCTD3, KCTD4, KCTD5, KCTD6, KCTD7, KCTD8, KCTD9, KDELC1, KDELC2, KDELR1,
KDELR2, KDELR3, KDF1, KDM1A, KDM1B, KDM2A, KDM2B, KDM3A, KDM3B,
KDM4A, KDM4B, KDM4C, KDM4D, KDM4E, KDM4F, KDM5A, KDM5B, KDM5C,
KDM5D, KDM6A, KDM6B, KDM7A, KDM8, KDR, KDSR, KEAP1, KEL, KERA,
KF459570.1, KHDC1, KHDC1L, KHDC3L, KHDRBS1, KHDRBS2, KHDRBS3, KHK,
KHNYN, KHSRP, KIAA0040, KIAA0100, KIAA0141, KIAA0232, KIAA0319, KIAA0319L,
KIAA0355, KIAA0368, KIAA0391, KIAA0408, KIAA0513, KIAA0556, KIAA0586,
KIAA0753, KIAA0825, KIAA0895, KIAA0895L, KIAA0907, KIAA0930, KIAA1024,
KIAA1024L, KIAA1107, KIAA1109, KIAA1143, KIAA1147, KIAA1161, KIAA1191,
KIAA1210, KIAA1211, KIAA1211L, KIAA1217, KIAA1257, KIAA1324, KIAA1324L,
KIAA1328, KIAA1456, KIAA1468, KIAA1522, KIAA1524, KIAA1549, KIAA1549L,
KIAA1551, KIAA1586, KIAA1614, KIAA1644, KIAA1671, KIAA1683, KIAA1755,
KIAA1841, KIAA1958, KIAA2012, KIAA2013, KIAA2026, KIDINS220, KIF11, KIF12,
KIF13A, KIF13B, KIF14, KIF15, KIF16B, KIF17, KIF18A, KIF18B, KIF19, KIF1A, KIF1B,
KIF1BP, KIFIC, KIF20A, KIF20B, KIF21A, KIF21B, KIF22, KIF23, KIF24, KIF25, KIF26A,
KIF26B, KIF27, KIF2A, KIF2B, KIF2C, KIF3A, KIF3B, KIF3C, KIF4A, KIF4B, KIF5A, KIF5B,
KIF5C, KIF6, KIF7, KIF9, KIFAP3, KIFC1, KIFC2, KIFC3, KIN, KIR2DL1, KIR2DL2,
KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DL5B, KIR2DP1, KIR2DS1, KIR2DS2, KIR2DS3,
KIR2DS4, KIR2DS5, KIR3DL1, KIR3DL2, KIR3DL3, KIR3DP1, KIR3DS1, KIR3DX1,
KIRREL1, KIRREL2, KIRREL3, KISS1, KISS1R, KIT, KITLG, KIZ, KL, KLB, KLC1, KLC2,
KLC3, KLC4, KLF1, KLF10, KLF11, KLF12, KLF13, KLF14, KLF15, KLF16, KLF17, KLF18,
KLF2, KLF3, KLF4, KLF5, KLF6, KLF7, KLF8, KLF9, KLHDC1, KLHDC10, KLHDC2,
KLHDC3, KLHDC4, KLHDC7A, KLHDC7B, KLHDC8A, KLHDC8B, KLHDC9, KLHL1,
KLHL10, KLHL11, KLHL12, KLHL13, KLHL14, KLHL15, KLHL17, KLHL18, KLHL2,
KLHL20, KLHL21, KLHL22, KLHL23, KLHL24, KLHL25, KLHL26, KLHL28, KLHL29,
KLHL3, KLHL30, KLHL31, KLHL32, KLHL33, KLHL34, KLHL35, KLHL36, KLHL38,
KLHL4, KLHL40, KLHL41, KLHL42, KLHL5, KLHL6, KLHL7, KLHL8, KLHL9, KLK1,
KLK10, KLK11, KLK12, KLK13, KLK14, KLK15, KLK2, KLK3, KLK4, KLK5, KLK6, KLK7,
KLK8, KLK9, KLKB1, KLLN, KLRB1, KLRC1, KLRC2, KLRC3, KLRC4, KLRC4-KLRK1,
KLRD1, KLRF1, KLRF2, KLRG1, KLRG2, KLRK1, KMO, KMT2A, KMT2B, KMT2C,
KMT2D, KMT2E, KMT5A, KMT5B, KMT5C, KNCN, KNDC1, KNG1, KNL1, KNOP1,
KNSTRN, KNTC1, KP420437.1, KP420437.2, KP420437.3, KP420439.1, KP420440.1,
KP420440.2, KP420440.3, KP420440.4, KP420440.5, KP420440.6, KP420440.7, KP420440.8,
KP420440.9, KP420441.1, KP420441.2, KP420441.3, KP420441.4, KP420441.5, KP420442.2,
KP420442.3, KP420443.1, KP420444.1, KP420444.2, KP420444.3, KP420444.4, KP420444.5,
KP420444.6, KP420444.7, KP420446.1, KP420446.2, KPNA1, KPNA2, KPNA3, KPNA4,
KPNA5, KPNA6, KPNA7, KPNB1, KPRP, KPTN, KRAS, KRBA1, KRBA2, KRBOX1,
KRBOX4, KRCC1, KREMEN1, KREMEN2, KRI1, KRIT1, KRR1, KRT1, KRT10, KRT12,
KRT13, KRT14, KRT15, KRT16, KRT17, KRT18, KRT19, KRT2, KRT20, KRT222, KRT23,
KRT24, KRT25, KRT26, KRT27, KRT28, KRT3, KRT31, KRT32, KRT33A, KRT33B, KRT34,
KRT35, KRT36, KRT37, KRT38, KRT39, KRT4, KRT40, KRT5, KRT6A, KRT6B, KRT6C,
KRT7, KRT71, KRT72, KRT73, KRT74, KRT75, KRT76, KRT77, KRT78, KRT79, KRT8,
KRT80, KRT81, KRT82, KRT83, KRT84, KRT85, KRT86, KRT9, KRTAP10-1, KRTAP10-10,
KRTAP10-11, KRTAP10-12, KRTAP10-2, KRTAP10-3, KRTAP10-4, KRTAP10-5, KRTAP10-
6, KRTAP10-7, KRTAP10-8, KRTAP10-9, KRTAP1-1, KRTAP11-1, KRTAP12-1, KRTAP12-
2, KRTAP12-3, KRTAP12-4, KRTAP1-3, KRTAP13-1, KRTAP13-2, KRTAP13-3, KRTAP13-
4, KRTAP1-4, KRTAP1-5, KRTAP15-1, KRTAP16-1, KRTAP17-1, KRTAP19-1, KRTAP19-2,
KRTAP19-3, KRTAP19-4, KRTAP19-5, KRTAP19-6, KRTAP19-7, KRTAP19-8, KRTAP20-1,
KRTAP20-2, KRTAP20-3, KRTAP20-4, KRTAP2-1, KRTAP21-1, KRTAP21-2, KRTAP21-3,
KRTAP2-2, KRTAP22-1, KRTAP22-2, KRTAP2-3, KRTAP23-1, KRTAP2-4, KRTAP24-1,
KRTAP25-1, KRTAP26-1, KRTAP27-1, KRTAP29-1, KRTAP3-1, KRTAP3-2, KRTAP3-3,
KRTAP4-1, KRTAP4-11, KRTAP4-12, KRTAP4-16, KRTAP4-2, KRTAP4-3, KRTAP4-4,
KRTAP4-5, KRTAP4-6, KRTAP4-7, KRTAP4-8, KRTAP4-9, KRTAP5-1, KRTAP5-10,
KRTAP5-11, KRTAP5-2, KRTAP5-3, KRTAP5-4, KRTAP5-5, KRTAP5-6, KRTAP5-7,
KRTAP5-8, KRTAP5-9, KRTAP6-1, KRTAP6-2, KRTAP6-3, KRTAP7-1, KRTAP8-1,
KRTAP9-1, KRTAP9-2, KRTAP9-3, KRTAP9-4, KRTAP9-6, KRTAP9-7, KRTAP9-8,
KRTAP9-9, KRTCAP2, KRTCAP3, KRTDAP, KSR1, KSR2, KTI12, KTN1, KU645196.1,
KU645196.2, KU645196.3, KU645196.4, KU645196.5, KU645196.6, KU645196.7,
KU645196.8, KU645196.9, KU645197.1, KU645197.2, KU645197.3, KU645197.4,
KU645197.5, KU645198.1, KXD1, KY, KYAT1, KYAT3, KYNU, LICAM, LITD1, L2HGDH,
L34079.1, L3HYPDH, L3MBTL1, L3MBTL2, L3MBTL3, L3MBTL4, LACC1, LACRT,
LACTB, LACTB2, LACTBL1, LAD1, LAG3, LAGE3, LAIR1, LAIR2, LALBA, LAMA1,
LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMB4, LAMC1, LAMC2,
LAMC3, LAMP1, LAMP2, LAMP3, LAMP5, LAMTOR1, LAMTOR2, LAMTOR3,
LAMTOR4, LAMTOR5, LANCL1, LANCL2, LANCL3, LAP3, LAPTM4A, LAPTM4B,
LAPTM5, LARGE1, LARGE2, LARP1, LARPIB, LARP4, LARP4B, LARP6, LARP7, LARS,
LARS2, LAS1L, LASP1, LAT, LAT2, LATS1, LATS2, LAX1, LAYN, LBH, LBHD1, LBP,
LBR, LBX1, LBX2, LCA5, LCA5L, LCAT, LCE1A, LCE1B, LCE1C, LCE1D, LCE1E, LCE1F,
LCE2A, LCE2B, LCE2C, LCE2D, LCE3A, LCE3B, LCE3C, LCE3D, LCE3E, LCE4A, LCE5A,
LCE6A, LCK, LCLAT1, LCMT1, LCMT2, LCN1, LCN10, LCN12, LCN15, LCN2, LCN6,
LCN8, LCN9, LCNL1, LCOR, LCORL, LCP1, LCP2, LCT, LCTL, LDAH, LDB1, LDB2, LDB3,
LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, LDHD, LDLR, LDLRAD1, LDLRAD2,
LDLRAD3, LDLRAD4, LDLRAP1, LDOC1, LEAP2, LECT2, LEF1, LEFTY1, LEFTY2,
LEKR1, LELP1, LEMD1, LEMD2, LEMD3, LENEP, LENG1, LENG8, LENG9, LEO1, LEP,
LEPR, LEPROT, LEPROTL1, LETM1, LETM2, LETMD1, LEUTX, LEXM, LFNG, LGALS1,
LGALS12, LGALS13, LGALS14, LGALS16, LGALS2, LGALS3, LGALS3BP, LGALS4,
LGALS7, LGALS7B, LGALS8, LGALS9, LGALS9B, LGALS9C, LGALSL, LGI1, LGI2, LGI3,
LGI4, LGMN, LGR4, LGR5, LGR6, LGSN, LHB, LHCGR, LHFPL1, LHFPL2, LHFPL3,
LHFPL4, LHFPL5, LHFPL6, LHPP, LHX1, LHX2, LHX3, LHX4, LHX5, LHX6, LHX8, LHX9,
LIAS, LIF, LIFR, LIG1, LIG3, LIG4, LILRA1, LILRA2, LILRA3, LILRA4, LILRA5, LILRA6,
LILRB1, LILRB2, LILRB3, LILRB4, LILRB5, LIM2, LIMA1, LIMCH1, LIMD1, LIMD2,
LIME1, LIMK1, LIMK2, LIMS1, LIMS2, LIMS3, LIMS4, LIN28A, LIN28B, LIN37, LIN52,
LIN54, LIN7A, LIN7B, LIN7C, LIN9, LINC00094, LINC00116, LINC00282, LINC00672,
LINC00675, LINC00694, LINC00854, LINC00890, LINC00959, LINC01125, LINC01556,
LINC02210-CRHR1, LINGO1, LINGO2, LINGO3, LINGO4, LINS1, LIPA, LIPC, LIPE, LIPF,
LIPG, LIPH, LIPI, LIPJ, LIPK, LIPM, LIPN, LIPT1, LIPT2, LITAF, LIX1, LIX1L, LKAAEAR1,
LLGL1, LLGL2, LLPH, LMAN1, LMAN1L, LMAN2, LMAN2L, LMBR1, LMBR1L,
LMBRD1, LMBRD2, LMCD1, LMF1, LMF2, LMLN, LMNA, LMNB1, LMNB2, LMNTD1,
LMNTD2, LMO1, LMO2, LMO3, LMO4, LMO7, LMO7DN, LMOD1, LMOD2, LMOD3,
LMTK2, LMTK3, LMXIA, LMX1B, LNP1, LNPEP, LNPK, LNX1, LNX2, LO000005.1,
LONP1, LONP2, LONRF1, LONRF2, LONRF3, LOR, LOX, LOXHD1, LOXL1, LOXL2,
LOXL3, LOXL4, LPA, LPAR1, LPAR2, LPAR3, LPAR4, LPAR5, LPAR6, LPCAT1, LPCAT2,
LPCAT3, LPCAT4, LPGAT1, LPIN1, LPIN2, LPIN3, LPL, LPO, LPP, LPXN, LRAT, LRBA,
LRCH1, LRCH2, LRCH3, LRCH4, LRCOL1, LRFN1, LRFN2, LRFN3, LRFN4, LRFN5, LRG1,
LRGUK, LRIF1, LRIG1, LRIG2, LRIG3, LRIT1, LRIT2, LRIT3, LRMDA, LRMP, LRP1,
LRP10, LRP11, LRP12, LRP1B, LRP2, LRP2BP, LRP3, LRP4, LRP5, LRP5L, LRP6, LRP8,
LRPAP1, LRPPRC, LRR1, LRRC1, LRRC10, LRRC10B, LRRC14, LRRC14B, LRRC15,
LRRC17, LRRC18, LRRC19, LRRC2, LRRC20, LRRC23, LRRC24, LRRC25, LRRC26,
LRRC27, LRRC28, LRRC29, LRRC3, LRRC30, LRRC31, LRRC32, LRRC34, LRRC36,
LRRC37A, LRRC37A2, LRRC37A3, LRRC37B, LRRC38, LRRC39, LRRC3B, LRRC3C,
LRRC4, LRRC40, LRRC41, LRRC42, LRRC43, LRRC45, LRRC46, LRRC47, LRRC49,
LRRC4B, LRRC4C, LRRC52, LRRC53, LRRC55, LRRC56, LRRC57, LRRC58, LRRC59,
LRRC6, LRRC61, LRRC63, LRRC66, LRRC69, LRRC7, LRRC70, LRRC71, LRRC72,
LRRC73, LRRC74A, LRRC74B, LRRC75A, LRRC75B, LRRC8A, LRRC8B, LRRC8C,
LRRC8D, LRRC8E, LRRC9, LRRCC1, LRRD1, LRRFIP1, LRRFIP2, LRRIQ1, LRRIQ3,
LRRIQ4, LRRK1, LRRK2, LRRN1, LRRN2, LRRN3, LRRN4, LRRN4CL, LRRTM1,
LRRTM2, LRRTM3, LRRTM4, LRSAM1, LRTM1, LRTM2, LRTOMT, LRWD1, LSAMP,
LSG1, LSM1, LSM10, LSM11, LSM12, LSM14A, LSM14B, LSM2, LSM3, LSM4, LSM5,
LSM6, LSM7, LSM8, LSMEM1, LSMEM2, LSP1, LSR, LSS, LST1, LTA, LTA4H, LTB,
LTB4R, LTB4R2, LTBP1, LTBP2, LTBP3, LTBP4, LTBR, LTC4S, LTF, LTK, LTN1, LTV1,
LUC7L, LUC7L2, LUC7L3, LUM, LURAP1, LURAP1L, LUZP1, LUZP2, LUZP4, LUZP6,
LVRN, LXN, LY6D, LY6E, LY6G5B, LY6G5C, LY6G6C, LY6G6D, LY6G6E, LY6G6F,
LY6H, LY6K, LY6L, LY75, LY75-CD302, LY86, LY9, LY96, LYAR, LYG1, LYG2, LYL1,
LYN, LYNX1, LYPD1, LYPD2, LYPD3, LYPD4, LYPD5, LYPD6, LYPD6B, LYPD8,
LYPLA1, LYPLA2, LYPLAL1, LYRM1, LYRM2, LYRM4, LYRM7, LYRM9, LYSMD1,
LYSMD2, LYSMD3, LYSMD4, LYST, LYVE1, LYZ, LYZL1, LYZL2, LYZL4, LYZL6, LZIC,
LZTFL1, LZTR1, LZTS1, LZTS2, LZTS3, MIAP, M6PR, MAATS1, MAB21L1, MAB21L2,
MAB21L3, MACC1, MACF1, MACROD1, MACROD2, MAD1L1, MAD2L1, MAD2L1BP,
MAD2L2, MADCAM1, MADD, MAEA, MAEL, MAF, MAF1, MAFA, MAFB, MAFF, MAFG,
MAFK, MAG, MAGEA1, MAGEA10, MAGEA11, MAGEA12, MAGEA2, MAGEA2B,
MAGEA3, MAGEA4, MAGEA6, MAGEA8, MAGEA9, MAGEA9B, MAGEB1, MAGEB10,
MAGEB16, MAGEB17, MAGEB18, MAGEB2, MAGEB3, MAGEB4, MAGEB5, MAGEB6,
MAGEB6P1, MAGEC1, MAGEC2, MAGEC3, MAGED1, MAGED2, MAGED4, MAGED4B,
MAGEE1, MAGEE2, MAGEF1, MAGEH1, MAGEL2, MAGI1, MAGI2, MAGI3, MAGIX,
MAGOH, MAGOHB, MAGT1, MAIP1, MAJIN, MAK, MAK16, MAL, MAL2, MALL,
MALRD1, MALSU1, MALT1, MAMDC2, MAMDC4, MAML1, MAML2, MAML3,
MAMLD1, MAMSTR, MANIA1, MANIA2, MANIB1, MANIC1, MAN2A1, MAN2A2,
MAN2B1, MAN2B2, MAN2C1, MANBA, MANBAL, MANEA, MANEAL, MANF, MANSC1,
MANSC4, MAOA, MAOB, MAP10, MAPIA, MAPIB, MAPILC3A, MAP1LC3B,
MAP1LC3B2, MAP1LC3C, MAPIS, MAP2, MAP2K1, MAP2K2, MAP2K3, MAP2K4,
MAP2K5, MAP2K6, MAP2K7, MAP3K1, MAP3K10, MAP3K11, MAP3K12, MAP3K13,
MAP3K14, MAP3K15, MAP3K19, MAP3K2, MAP3K20, MAP3K21, MAP3K3, MAP3K4,
MAP3K5, MAP3K6, MAP3K7, MAP3K7CL, MAP3K8, MAP3K9, MAP4, MAP4K1, MAP4K2,
MAP4K3, MAP4K4, MAP4K5, MAP6, MAP6D1, MAP7, MAP7D1, MAP7D2, MAP7D3,
MAP9, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK15, MAPK1IP1L,
MAPK3, MAPK4, MAPK6, MAPK7, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9,
MAPKAP1, MAPKAPK2, MAPKAPK3, MAPKAPK5, MAPKBP1, MAPRE1, MAPRE2,
MAPRE3, MAPT, MARC1, MARC2, MARCH1, MARCH10, MARCH11, MARCH2,
MARCH3, MARCH4, MARCH5, MARCH6, MARCH7, MARCH8, MARCH9, MARCKS,
MARCKSL1, MARCO, MARF1, MARK1, MARK2, MARK3, MARK4, MARS, MARS2,
MARVELD1, MARVELD2, MARVELD3, MAS1, MAS1L, MASP1, MASP2, MAST1,
MAST2, MAST3, MAST4, MASTL, MATIA, MAT2A, MAT2B, MATK, MATN1, MATN2,
MATN3, MATN4, MATR3, MAU2, MAVS, MAX, MAZ, MB, MB21D1, MB21D2, MBD1,
MBD2, MBD3, MBD3L1, MBD3L2, MBD3L2B, MBD3L3, MBD3L4, MBD3L5, MBD4,
MBD5, MBD6, MBIP, MBL2, MBLAC1, MBLAC2, MBNL1, MBNL2, MBNL3, MBOAT1,
MBOAT2, MBOAT4, MBOAT7, MBP, MBTD1, MBTPS1, MBTPS2, MC1R, MC2R, MC3R,
MC4R, MC5R, MCAM, MCAT, MCC, MCCC1, MCCC2, MCCD1, MCEE, MCEMP1, MCF2,
MCF2L, MCF2L2, MCFD2, MCHR1, MCHR2, MCIDAS, MCL1, MCM10, MCM2, MCM3,
MCM3 AP, MCM4, MCM5, MCM6, MCM7, MCM8, MCM9, MCMBP, MCMDC2, MCOLN1,
MCOLN2, MCOLN3, MCPH1, MCRIP1, MCRIP2, MCRS1, MCTP1, MCTP2, MCTS1, MCU,
MCUB, MCUR1, MDC1, MDFI, MDFIC, MDFIC2, MDGA1, MDGA2, MDH1, MDHIB,
MDH2, MDK, MDM1, MDM2, MDM4, MDN1, MDP1, MDS2, ME1, ME2, ME3, MEA1,
MEAF6, MECOM, MECP2, MECR, MED1, MED10, MED11, MED12, MED12L, MED13,
MED13L, MED14, MED14OS, MED15, MED16, MED17, MED18, MED19, MED20, MED21,
MED22, MED23, MED24, MED25, MED26, MED27, MED28, MED29, MED30, MED31,
MED4, MED6, MED7, MED8, MED9, MEDAG, MEF2A, MEF2B, MEF2C, MEF2D, MEFV,
MEGF10, MEGF11, MEGF6, MEGF8, MEGF9, MEI1, MEI4, MEIG1, MEIKIN, MEIOB,
MEIOC, MEIS1, MEIS2, MEIS3, MELK, MELTF, MEMO1, MEN1, MEOX1, MEOX2,
MEP1A, MEP1B, MEPCE, MEPE, MERTK, MESD, MESP1, MESP2, MEST, MET, METAP1,
METAPID, METAP2, METRN, METRNL, METTL1, METTL11B, METTL12, METTL13,
METTL14, METTL15, METTL16, METTL17, METTL18, METTL21A, METTL21C,
METTL22, METTL23, METTL24, METTL25, METTL26, METTL27, METTL2A, METTL2B,
METTL3, METTL4, METTL5, METTL6, METTL7A, METTL7B, METTL8, METTL9,
MEX3A, MEX3B, MEX3C, MEX3D, MFAP1, MFAP2, MFAP3, MFAP3L, MFAP4, MFAP5,
MFF, MFGE8, MFHAS1, MFN1, MFN2, MFNG, MFRP, MFSD1, MFSD10, MFSD11,
MFSD12, MFSD13A, MFSD14A, MFSD14B, MFSD14C, MFSD2A, MFSD2B, MFSD3,
MFSD4A, MFSD4B, MFSD5, MFSD6, MFSD6L, MFSD7, MFSD8, MFSD9, MGA, MGAM,
MGAM2, MGARP, MGAT1, MGAT2, MGAT3, MGAT4A, MGAT4B, MGAT4C, MGAT4D,
MGAT5, MGAT5B, MGEA5, MGLL, MGME1, MGMT, MGP, MGRN1, MGST1, MGST2,
MGST3, MIA, MIA3, MIA-RAB4B, MIB1, MIB2, MICA, MICAL1, MICAL2, MICAL3,
MICALCL, MICALL1, MICALL2, MICB, MICU1, MICU2, MICU3, MID1, MID1IP1, MID2,
MIDN, MIEF1, MIEF2, MIEN1, MIER1, MIER2, MIER3, MIF, MIF4GD, MIGA1, MIGA2,
MIIP, MILR1, MINDY1, MINDY2, MINDY3, MINDY4, MINDY4B, MINK1, MINOS1,
MINOS1-NBL1, MINPP1, MIOS, MIOX, MIP, MIPEP, MIPOL1, MIS12, MIS18A, MIS18BP1,
MISP, MISP3, MITD1, MITF, MIXL1, MKI67, MKKS, MKL1, MKL2, MKLN1, MKNK1,
MKNK2, MKRN1, MKRN2, MKRN2OS, MKRN3, MKS1, MKX, MLANA, MLC1, MLEC,
MLF1, MLF2, MLH1, MLH3, MLIP, MLKL, MLLT1, MLLT10, MLLT11, MLLT3, MLLT6,
MLN, MLNR, MLPH, MLST8, MLX, MLXIP, MLXIPL, MLYCD, MMAA, MMAB,
MMACHC, MMADHC, MMD, MMD2, MME, MMEL1, MMGT1, MMP1, MMP10, MMP11,
MMP12, MMP13, MMP14, MMP15, MMP16, MMP17, MMP19, MMP2, MMP20, MMP21,
MMP23B, MMP24, MMP24-AS1, MMP25, MMP26, MMP27, MMP28, MMP3, MMP7, MMP8,
MMP9, MMRN1, MMRN2, MMS19, MMS22L, MN1, MNAT1, MND1, MNDA, MNS1, MNT,
MNX1, MOAP1, MOBIA, MOBIB, MOB2, MOB3A, MOB3B, MOB3C, MOB4, MOBP,
MOCOS, MOCS1, MOCS2, MOCS3, MOG, MOGAT1, MOGAT2, MOGAT3, MOGS, MOK,
MONIA, MONIB, MON2, MORC1, MORC2, MORC3, MORC4, MORF4L1, MORF4L2,
MORN1, MORN2, MORN3, MORN4, MORN5, MOS, MOSPD1, MOSPD2, MOSPD3,
MOV10, MOVIOL1, MOXD1, MPC1, MPC1L, MPC2, MPDU1, MPDZ, MPEG1, MPG,
MPHOSPH10, MPHOSPH6, MPHOSPH8, MPHOSPH9, MPI, MPIG6B, MPL, MPLKIP,
MPND, MPO, MPP1, MPP2, MPP3, MPP4, MPP5, MPP6, MPP7, MPPE1, MPPED1, MPPED2,
MPRIP, MPST, MPV17, MPV17L, MPV17L2, MPZ, MPZL1, MPZL2, MPZL3, MR1, MRAP,
MRAP2, MRAS, MRC1, MRC2, MRE11, MREG, MRFAP1, MRFAP1L1, MRGBP, MRGPRD,
MRGPRE, MRGPRF, MRGPRG, MRGPRX1, MRGPRX2, MRGPRX3, MRGPRX4, MRI1,
MRLN, MRM1, MRM2, MRM3, MRNIP, MRO, MROH1, MROH2A, MROH2B, MROH5,
MROH6, MROH7, MROH7-TTC4, MROH8, MROH9, MRPL1, MRPL10, MRPL11, MRPL12,
MRPL13, MRPL14, MRPL15, MRPL16, MRPL17, MRPL18, MRPL19, MRPL2, MRPL20,
MRPL21, MRPL22, MRPL23, MRPL24, MRPL27, MRPL28, MRPL3, MRPL30, MRPL32,
MRPL33, MRPL34, MRPL35, MRPL36, MRPL37, MRPL38, MRPL39, MRPL4, MRPL40,
MRPL41, MRPL42, MRPL43, MRPL44, MRPL45, MRPL46, MRPL47, MRPL48, MRPL49,
MRPL50, MRPL51, MRPL52, MRPL53, MRPL54, MRPL55, MRPL57, MRPL58, MRPL9,
MRPS10, MRPS11, MRPS12, MRPS14, MRPS15, MRPS16, MRPS17, MRPS18A, MRPS18B,
MRPS18C, MRPS2, MRPS21, MRPS22, MRPS23, MRPS24, MRPS25, MRPS26, MRPS27,
MRPS28, MRPS30, MRPS31, MRPS33, MRPS34, MRPS35, MRPS36, MRPS5, MRPS6,
MRPS7, MRPS9, MRRF, MRS2, MRTO4, MRVI1, MS4A1, MS4A10, MS4A12, MS4A13,
MS4A14, MS4A15, MS4A2, MS4A3, MS4A4A, MS4A4E, MS4A5, MS4A6A, MS4A6E,
MS4A7, MS4A8, MSANTD1, MSANTD2, MSANTD3, MSANTD3-TMEFF1, MSANTD4,
MSC, MSGN1, MSH2, MSH3, MSH4, MSH5, MSH5-SAPCD1, MSH6, MSI1, MSI2, MSL1,
MSL2, MSL3, MSLN, MSLNL, MSMB, MSMO1, MSMP, MSN, MSR1, MSRA, MSRB1,
MSRB2, MSRB3, MSS51, MST1, MSTIR, MSTN, MSTO1, MSX1, MSX2, MTIA, MT1B,
MTIE, MTIF, MT1G, MTIH, MT1HL1, MTIM, MT1X, MT2A, MT3, MT4, MTA1, MTA2,
MTA3, MTAP, MT-ATP6, MT-ATP8, MTBP, MTCH1, MTCH2, MTCL1, MT-CO1, MT-CO2,
MT-CO3, MTCP1, MT-CYB, MTDH, MTERF1, MTERF2, MTERF3, MTERF4, MTF1, MTF2,
MTFMT, MTFP1, MTFR1, MTFR1L, MTFR2, MTG1, MTG2, MTHFD1, MTHFD1L,
MTHFD2, MTHFD2L, MTHFR, MTHFS, MTHFSD, MTIF2, MTIF3, MTM1, MTMR1,
MTMR10, MTMR11, MTMR12, MTMR14, MTMR2, MTMR3, MTMR4, MTMR6, MTMR7,
MTMR8, MTMR9, MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-ND4L, MT-ND5, MT-ND6,
MTNRIA, MTNR1B, MTO1, MTOR, MTPAP, MTPN, MTR, MTRF1, MTRF1L, MTRNR2L1,
MTRNR2L10, MTRNR2L11, MTRNR2L12, MTRNR2L13, MTRNR2L3, MTRNR2L4,
MTRNR2L5, MTRNR2L6, MTRNR2L7, MTRNR2L8, MTRR, MTSS1, MTSS1L, MTTP,
MTURN, MTUS1, MTUS2, MTX1, MTX2, MTX3, MUC1, MUC12, MUC13, MUC15, MUC16,
MUC17, MUC2, MUC20, MUC21, MUC22, MUC3A, MUC4, MUC5AC, MUC5B, MUC6,
MUC7, MUCL1, MUL1, MUM1, MUM1L1, MUS81, MUSK, MUSTN1, MUT, MUTYH,
MVB12A, MVB12B, MVD, MVK, MVP, MX1, MX2, MXD1, MXD3, MXD4, MXI1, MXRA5,
MXRA7, MXRA8, MYADM, MYADML2, MYB, MYBBPIA, MYBL1, MYBL2, MYBPC1,
MYBPC2, MYBPC3, MYBPH, MYBPHL, MYC, MYCBP, MYCBP2, MYCBPAP, MYCL,
MYCN, MYCT1, MYD88, MYDGF, MYEF2, MYEOV, MYF5, MYF6, MYH1, MYH10,
MYH11, MYH13, MYH14, MYH15, MYH2, MYH3, MYH4, MYH6, MYH7, MYH7B, MYH8,
MYH9, MYL1, MYL10, MYL12A, MYL12B, MYL2, MYL3, MYL4, MYL5, MYL6, MYL6B,
MYL7, MYL9, MYLIP, MYLK, MYLK2, MYLK3, MYLK4, MYLPF, MYMK, MYMX,
MYNN, MYO10, MYO15A, MYO15B, MYO16, MYO18A, MYO18B, MYO19, MYO1A,
MYO1B, MYO1C, MYOID, MYO1E, MYOIF, MYO1G, MYO1H, MYO3A, MYO3B,
MY05A, MYO5B, MYO5C, MYO6, MYO7A, MYO7B, MYO9A, MYO9B, MYOC, MYOCD,
MYOCOS, MYOD1, MYOF, MYOG, MYOM1, MYOM2, MYOM3, MYOT, MYOZ1, MYOZ2,
MYOZ3, MYPN, MYPOP, MYRF, MYRFL, MYRIP, MYSM1, MYT1, MYT1L, MYZAP,
MZB1, MZF1, MZT1, MZT2A, MZT2B, N4BP1, N4BP2, N4BP2L1, N4BP2L2, N4BP3,
N6AMT1, NAA10, NAA11, NAA15, NAA16, NAA20, NAA25, NAA30, NAA35, NAA38,
NAA40, NAA50, NAA60, NAAA, NAALAD2, NAALADL1, NAALADL2, NAB1, NAB2,
NABP1, NABP2, NACA, NACA2, NACAD, NACC1, NACC2, NADK, NADK2, NADSYN1,
NAE1, NAF1, NAGA, NAGK, NAGLU, NAGPA, NAGS, NAIF1, NAIP, NALCN, NAMPT,
NANOG, NANOGNB, NANOGP8, NANOS1, NANOS2, NANOS3, NANP, NANS, NAP1L1,
NAP1L2, NAP1L3, NAP1L4, NAP1L5, NAPA, NAPB, NAPEPLD, NAPG, NAPRT, NAPSA,
NARF, NARFL, NARS, NARS2, NASP, NAT1, NAT10, NAT14, NAT16, NAT2, NAT6, NAT8,
NAT8B, NAT8L, NAT9, NATD1, NAV1, NAV2, NAV3, NAXD, NAXE, NBAS, NBDY,
NBEA, NBEAL1, NBEAL2, NBL1, NBN, NBPF1, NBPF10, NBPF11, NBPF12, NBPF14,
NBPF15, NBPF19, NBPF20, NBPF26, NBPF3, NBPF4, NBPF6, NBPF9, NBR1, NCALD,
NCAM1, NCAM2, NCAN, NCAPD2, NCAPD3, NCAPG, NCAPG2, NCAPH, NCAPH2,
NCBP1, NCBP2, NCBP2-AS2, NCBP2L, NCBP3, NCCRP1, NCDN, NCEH1, NCF1, NCF2,
NCF4, NCK1, NCK2, NCKAP1, NCKAP1L, NCKAP5, NCKAP5L, NCKIPSD, NCL, NCLN,
NCMAP, NCOA1, NCOA2, NCOA3, NCOA4, NCOA5, NCOA6, NCOA7, NCOR1, NCOR2,
NCR1, NCR2, NCR3, NCR3LG1, NCS1, NCSTN, NDC1, NDC80, NDE1, NDEL1, NDFIP1,
NDFIP2, NDN, NDNF, NDOR1, NDP, NDRG1, NDRG2, NDRG3, NDRG4, NDST1, NDST2,
NDST3, NDST4, NDUFA1, NDUFA10, NDUFA11, NDUFA12, NDUFA13, NDUFA2,
NDUFA3, NDUFA4, NDUFA4L2, NDUFA5, NDUFA6, NDUFA7, NDUFA8, NDUFA9,
NDUFAB1, NDUFAF1, NDUFAF2, NDUFAF3, NDUFAF4, NDUFAF5, NDUFAF6,
NDUFAF7, NDUFAF8, NDUFB1, NDUFB10, NDUFB11, NDUFB2, NDUFB3, NDUFB4,
NDUFB5, NDUFB6, NDUFB7, NDUFB8, NDUFB9, NDUFC1, NDUFC2, NDUFC2-KCTD14,
NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS5, NDUFS6, NDUFS7, NDUFS8, NDUFV1,
NDUFV2, NDUFV3, NEB, NEBL, NECAB1, NECAB2, NECAB3, NECAP1, NECAP2,
NECTIN1, NECTIN2, NECTIN3, NECTIN4, NEDD1, NEDD4, NEDD4L, NEDD8, NEDD8-
MDP1, NEDD9, NEFH, NEFL, NEFM, NEGR1, NEIL1, NEIL2, NEIL3, NEK1, NEK10,
NEK11, NEK2, NEK3, NEK4, NEK5, NEK6, NEK7, NEK8, NEK9, NELFA, NELFB, NELFCD,
NELFE, NELL1, NELL2, NEMF, NEMP1, NEMP2, NENF, NEO1, NEPRO, NES, NET1,
NETO1, NETO2, NEU1, NEU2, NEU3, NEU4, NEURL1, NEURLIB, NEURL2, NEURL3,
NEURL4, NEUROD1, NEUROD2, NEUROD4, NEUROD6, NEUROG1, NEUROG2,
NEUROG3, NEXMIF, NEXN, NF1, NF2, NFAM1, NFASC, NFAT5, NFATC1, NFATC2,
NFATC2IP, NFATC3, NFATC4, NFE2, NFE2L1, NFE2L2, NFE2L3, NFE4, NFIA, NFIB,
NFIC, NFIL3, NFIX, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBID, NFKBIE, NFKBIL1,
NFKBIZ, NFRKB, NFS1, NFU1, NFX1, NFXL1, NFYA, NFYB, NFYC, NGB, NGDN, NGEF,
NGF, NGFR, NGLY1, NGRN, NHEJ1, NHLH1, NHLH2, NHLRC1, NHLRC2, NHLRC3,
NHLRC4, NHP2, NHS, NHSL1, NHSL2, NICN1, NID1, NID2, NIF3L1, NIFK, NIMIK, NIN,
NINJ1, NINJ2, NINL, NIP7, NIPA1, NIPA2, NIPAL1, NIPAL2, NIPAL3, NIPAL4, NIPBL,
NIPSNAP1, NIPSNAP2, NIPSNAP3A, NIPSNAP3B, NISCH, NIT1, NIT2, NKAIN1, NKAIN2,
NKAIN3, NKAIN4, NKAP, NKAPL, NKD1, NKD2, NKG7, NKIRAS1, NKIRAS2, NKPD1,
NKRF, NKTR, NKX1-1, NKX1-2, NKX2-1, NKX2-2, NKX2-3, NKX2-4, NKX2-5, NKX2-6,
NKX2-8, NKX3-1, NKX3-2, NKX6-1, NKX6-2, NKX6-3, NLE1, NLGN1, NLGN2, NLGN3,
NLGN4X, NLGN4Y, NLK, NLN, NLRC3, NLRC4, NLRC5, NLRP1, NLRP10, NLRP11,
NLRP12, NLRP13, NLRP14, NLRP2, NLRP2B, NLRP3, NLRP4, NLRP5, NLRP6, NLRP7,
NLRP8, NLRP9, NLRX1, NMB, NMBR, NMD3, NME1, NME1-NME2, NME2, NME3, NME4,
NME5, NME6, NME7, NME8, NME9, NMI, NMNAT1, NMNAT2, NMNAT3, NMRAL1,
NMRK1, NMRK2, NMS, NMT1, NMT2, NMU, NMUR1, NMUR2, NNAT, NNMT, NNT,
NOA1, NOB1, NOBOX, NOC2L, NOC3L, NOC4L, NOCT, NOD1, NOD2, NODAL, NOG,
NOL10, NOL11, NOL12, NOL3, NOL4, NOL4L, NOL6, NOL7, NOL8, NOL9, NOLC1, NOM1,
NOMO1, NOMO2, NOMO3, NONO, NOP10, NOP14, NOP16, NOP2, NOP53, NOP56, NOP58,
NOP9, NOS1, NOS1AP, NOS2, NOS3, NOSIP, NOSTRIN, NOTCH1, NOTCH2, NOTCH2NL,
NOTCH3, NOTCH4, NOTO, NOTUM, NOV, NOVA1, NOVA2, NOX1, NOX3, NOX4, NOX5,
NOXA1, NOX01, NOXRED1, NPAP1, NPAS1, NPAS2, NPAS3, NPAS4, NPAT, NPB,
NPBWR1, NPBWR2, NPC1, NPC1L1, NPC2, NPDC1, NPEPL1, NPEPPS, NPFF, NPFFR1,
NPFFR2, NPHP1, NPHP3, NPHP3-ACAD11, NPHP4, NPHS1, NPHS2, NPIPA1, NPIPA2,
NPIPA3, NPIPA5, NPIPA7, NPIPA8, NPIPB11, NPIPB12, NPIPB13, NPIPB15, NPIPB2,
NPIPB3, NPIPB4, NPIPB5, NPIPB6, NPIPB7, NPIPB8, NPIPB9, NPL, NPLOC4, NPM1, NPM2,
NPM3, NPNT, NPPA, NPPB, NPPC, NPR1, NPR2, NPR3, NPRL2, NPRL3, NPS, NPSR1,
NPTN, NPTX1, NPTX2, NPTXR, NPVF, NPW, NPY, NPY1R, NPY2R, NPY4R, NPY4R2,
NPY5R, NQO1, NQ02, NROB1, NROB2, NR1D1, NR1D2, NR1H2, NR1H3, NR1H4, NR1I2,
NR113, NR2C1, NR2C2, NR2C2AP, NR2E1, NR2E3, NR2F1, NR2F2, NR2F6, NR3C1, NR3C2,
NR4A1, NR4A2, NR4A3, NR5A1, NR5A2, NR6A1, NRAP, NRARP, NRAS, NRBF2, NRBP1,
NRBP2, NRCAM, NRDC, NRDE2, NREP, NRF1, NRG1, NRG2, NRG3, NRG4, NRGN, NRIP1,
NRIP2, NRIP3, NRK, NRL, NRM, NRN1, NRN1L, NRP1, NRP2, NRROS, NRSN1, NRSN2,
NRTN, NRXN1, NRXN2, NRXN3, NSA2, NSD1, NSD2, NSD3, NSDHL, NSF, NSFL1C, NSL1,
NSMAF, NSMCE1, NSMCE2, NSMCE3, NSMCE4A, NSMF, NSRP1, NSUN2, NSUN3,
NSUN4, NSUN5, NSUN6, NSUN7, NT5C, NT5CIA, NT5C1B, NT5C1B-RDH14, NT5C2,
NT5C3A, NT5C3B, NT5DC1, NT5DC2, NT5DC3, NT5DC4, NT5E, NT5M, NTAN1, NTF3,
NTF4, NTHL1, NTM, NTMT1, NTN1, NTN3, NTN4, NTN5, NTNG1, NTNG2, NTPCR,
NTRK1, NTRK2, NTRK3, NTS, NTSR1, NTSR2, NUAK1, NUAK2, NUB1, NUBP1, NUBP2,
NUBPL, NUCB1, NUCB2, NUCKS1, NUDC, NUDCD1, NUDCD2, NUDCD3, NUDT1,
NUDT10, NUDT11, NUDT12, NUDT13, NUDT14, NUDT15, NUDT16, NUDT16L1, NUDT17,
NUDT18, NUDT19, NUDT2, NUDT21, NUDT22, NUDT3, NUDT4, NUDT4P1, NUDT5,
NUDT6, NUDT7, NUDT8, NUDT9, NUF2, NUFIP1, NUFIP2, NUGGC, NUMA1, NUMB,
NUMBL, NUP107, NUP133, NUP153, NUP155, NUP160, NUP188, NUP205, NUP210,
NUP210L, NUP214, NUP35, NUP37, NUP43, NUP50, NUP54, NUP58, NUP62, NUP62CL,
NUP85, NUP88, NUP93, NUP98, NUPL2, NUPR1, NUPR2, NUS1, NUSAP1, NUTF2, NUTM1,
NUTM2A, NUTM2B, NUTM2D, NUTM2E, NUTM2F, NUTM2G, NVL, NWD1, NWD2,
NXF1, NXF2, NXF2B, NXF3, NXF5, NXN, NXNL1, NXNL2, NXPE1, NXPE2, NXPE3,
NXPE4, NXPH1, NXPH2, NXPH3, NXPH4, NXT1, NXT2, NYAP1, NYAP2, NYNRIN, NYX,
OAF, OARD1, OAS1, OAS2, OAS3, OASL, OAT, OAZ1, OAZ2, OAZ3, OBP2A, OBP2B,
OBSCN, OBSCN-AS1, OBSL1, OC90, OCA2, OCEL1, OCIAD1, OCIAD2, OCLM, OCLN,
OCM, OCM2, OCRL, OCSTAMP, ODAM, ODC1, ODF1, ODF2, ODF2L, ODF3, ODF3B,
ODF3L1, ODF3L2, ODF4, OFCC1, OFD1, OGDH, OGDHL, OGFOD1, OGFOD2, OGFOD3,
OGFR, OGFRL1, OGG1, OGN, OGT, OIP5, OIT3, OLA1, OLAH, OLFM1, OLFM2, OLFM3,
OLFM4, OLFML1, OLFML2A, OLFML2B, OLFML3, OLIG1, OLIG2, OLIG3, OLR1, OMA1,
OMD, OMG, OMP, ONECUT1, ONECUT2, ONECUT3, OOEP, OOSP2, OPA1, OPA3,
OPALIN, OPCML, OPHN1, OPLAH, OPN1LW, OPN1MW, OPN1MW2, OPN1MW3,
OPN1SW, OPN3, OPN4, OPN5, OPRD1, OPRK1, OPRL1, OPRM1, OPRPN, OPTC, OPTN,
OR10A2, OR10A3, OR10A4, OR10A5, OR10A6, OR10A7, OR10AC1, OR10AD1, OR10AG1,
OR10C1, OR10D3, OR10G2, OR10G3, OR10G4, OR10G6, OR10G7, OR10G8, OR10G9,
OR10H1, OR10H2, OR10H3, OR10H4, OR10H5, OR10J1, OR10J3, OR10J4, OR10J5, OR10K1,
OR10K2, OR10P1, OR10Q1, OR10R2, OR10S1, OR10T2, OR10V1, OR10W1, OR10X1,
OR10Z1, OR11A1, OR11G2, OR11H1, OR11H12, OR11H2, OR11H4, OR11H6, OR11H7,
OR11L1, OR12D1, OR12D2, OR12D3, OR13A1, OR13C2, OR13C3, OR13C4, OR13C5,
OR13C7, OR13C8, OR13C9, OR13D1, OR13F1, OR13G1, OR13H1, OR13J1, OR14A16,
OR14A2, OR14C36, OR14I1, OR14J1, OR14K1, OR1A1, OR1A2, OR1B1, OR1C1, OR1D2,
OR1D5, OR1E1, OR1E2, OR1F1, OR1G1, OR1I1, OR1J1, OR1J2, OR1J4, OR1K1, OR1L1,
OR1L3, OR1L4, OR1L6, OR1L8, OR1M1, OR1N1, OR1N2, OR1P1, OR1Q1, OR1S1, OR1S2,
OR2A1, OR2A12, OR2A14, OR2A2, OR2A25, OR2A4, OR2A42, OR2A5, OR2A7, OR2AE1,
OR2AG1, OR2AG2, OR2AJ1, OR2AK2, OR2AP1, OR2AT4, OR2B11, OR2B2, OR2B3,
OR2B6, OR2C1, OR2C3, OR2D2, OR2D3, OR2F1, OR2F2, OR2G2, OR2G3, OR2G6, OR2H1,
OR2H2, OR2J1, OR2J2, OR2J3, OR2K2, OR2L13, OR2L2, OR2L3, OR2L5, OR2L8, OR2M2,
OR2M3, OR2M4, OR2M5, OR2M7, OR2S2, OR2T1, OR2T10, OR2T11, OR2T12, OR2T2,
OR2T27, OR2T29, OR2T3, OR2T33, OR2T34, OR2T35, OR2T4, OR2T5, OR2T6, OR2T7,
OR2T8, OR2V1, OR2V2, OR2W1, OR2W3, OR2Y1, OR2Z1, OR3A1, OR3A2, OR3A3,
OR4A15, OR4A16, OR4A47, OR4A5, OR4A8, OR4B1, OR4C11, OR4C12, OR4C13, OR4C15,
OR4C16, OR4C3, OR4C45, OR4C46, OR4C5, OR4C6, OR4D1, OR4D10, OR4D11, OR4D2,
OR4D5, OR4D6, OR4D9, OR4E1, OR4E2, OR4F15, OR4F16, OR4F17, OR4F21, OR4F29,
OR4F3, OR4F4, OR4F5, OR4F6, OR4K1, OR4K13, OR4K14, OR4K15, OR4K17, OR4K2,
OR4K3, OR4K5, OR4L1, OR4M1, OR4M2, OR4N2, OR4N4, OR4N5, OR4P4, OR4Q2, OR4Q3,
OR4S1, OR4S2, OR4X1, OR4X2, OR51A2, OR51A4, OR51A7, OR51B2, OR51B4, OR51B5,
OR51B6, OR51D1, OR51E1, OR51E2, OR51F1, OR51F2, OR51G1, OR51G2, OR51H1,
OR5111, OR5112, OR51J1, OR51L1, OR51M1, OR51Q1, OR51S1, OR51T1, OR51V1, OR52A1,
OR52A5, OR52B2, OR52B4, OR52B6, OR52D1, OR52E2, OR52E4, OR52E5, OR52E6,
OR52E8, OR52H1, OR5211, OR5212, OR52J3, OR52K1, OR52K2, OR52L1, OR52M1,
OR52N1, OR52N2, OR52N4, OR52N5, OR52R1, OR52W1, OR52Z1, OR56A1, OR56A3,
OR56A4, OR56A5, OR56B1, OR56B4, OR5A1, OR5A2, OR5AC1, OR5AC2, OR5AK2,
OR5AN1, OR5AP2, OR5AR1, OR5AS1, OR5AU1, OR5B12, OR5B17, OR5B2, OR5B21,
OR5B3, OR5C1, OR5D13, OR5D14, OR5D16, OR5D18, OR5F1, OR5G3, OR5H1, OR5H14,
OR5H15, OR5H2, OR5H6, OR5H8, OR511, OR5J2, OR5K1, OR5K2, OR5K3, OR5K4, OR5L1,
OR5L2, OR5M1, OR5M10, OR5M11, OR5M3, OR5M8, OR5M9, OR5P2, OR5P3, OR5R1,
OR5T1, OR5T2, OR5T3, OR5V1, OR5W2, OR6A2, OR6B1, OR6B2, OR6B3, OR6C1, OR6C2,
OR6C3, OR6C4, OR6C6, OR6C65, OR6C68, OR6C70, OR6C74, OR6C75, OR6C76, OR6F1,
OR6J1, OR6K2, OR6K3, OR6K6, OR6M1, OR6N1, OR6N2, OR6P1, OR6Q1, OR6S1, OR6T1,
OR6V1, OR6X1, OR6Y1, OR7A10, OR7A17, OR7A5, OR7C1, OR7C2, OR7D2, OR7D4,
OR7E24, OR7G1, OR7G2, OR7G3, OR8A1, OR8B12, OR8B2, OR8B3, OR8B4, OR8B8,
OR8D1, OR8D2, OR8D4, OR8G1, OR8G5, OR8H1, OR8H2, OR8H3, OR812, OR8J1, OR8J2,
OR8J3, OR8K1, OR8K3, OR8K5, OR8S1, OR8U1, OR8U8, OR9A2, OR9A4, OR9G1, OR9G4,
OR9G9, OR9HIP, OR9I1, OR9K2, OR9Q1, OR9Q2, ORAI1, ORAI2, ORAI3, ORAOV1, ORC1,
ORC2, ORC3, ORC4, ORC5, ORC6, ORM1, ORM2, ORMDL1, ORMDL2, ORMDL3, OS9,
OSBP, OSBP2, OSBPL10, OSBPL11, OSBPL1A, OSBPL2, OSBPL3, OSBPL5, OSBPL6,
OSBPL7, OSBPL8, OSBPL9, OSCAR, OSCP1, OSER1, OSGEP, OSGEPL1, OSGIN1, OSGIN2,
OSM, OSMR, OSR1, OSR2, OST4, OSTC, OSTF1, OSTM1, OSTN, OTC, OTOA, OTOF,
OTOG, OTOGL, OTOL1, OTOP1, OTOP2, OTOP3, OTOR, OTOS, OTP, OTUB1, OTUB2,
OTUD1, OTUD3, OTUD4, OTUD5, OTUD6A, OTUD6B, OTUD7A, OTUD7B, OTULIN,
OTX1, OTX2, OVCA2, OVCH1, OVCH2, OVGP1, OVOL1, OVOL2, OVOL3, OXA1L,
OXCT1, OXCT2, OXER1, OXGR1, OXLD1, OXNAD1, OXR1, OXSM, OXSR1, OXT, OXTR,
P2RX1, P2RX2, P2RX3, P2RX4, P2RX5, P2RX5-TAXIBP3, P2RX6, P2RX7, P2RY1, P2RY10,
P2RY11, P2RY12, P2RY13, P2RY14, P2RY2, P2RY4, P2RY6, P2RY8, P3H1, P3H2, P3H3,
P3H4, P4HA1, P4HA2, P4HA3, P4HB, P4HTM, PA2G4, PAAF1, PABPC1, PABPC1L,
PABPC1L2A, PABPC1L2B, PABPC3, PABPC4, PABPC4L, PABPC5, PABPN1, PABPN1L,
PACRG, PACRGL, PACS1, PACS2, PACSIN1, PACSIN2, PACSIN3, PADI1, PADI2, PADI3,
PADI4, PADI6, PAEP, PAF1, PAFAHIB1, PAFAHIB2, PAFAHIB3, PAFAH2, PAG1, PAGE1,
PAGE2, PAGE2B, PAGE3, PAGE4, PAGES, PAGR1, PAH, PAICS, PAIP1, PAIP2, PAIP2B,
PAK1, PAK1IP1, PAK2, PAK3, PAK4, PAK5, PAK6, PALB2, PALD1, PALLD, PALM,
PALM2, PALM2-AKAP2, PALM3, PALMD, PAM, PAM16, PAMR1, PAN2, PAN3, PANK1,
PANK2, PANK3, PANK4, PANO1, PANX1, PANX2, PANX3, PAOX, PAPD4, PAPD5,
PAPD7, PAPLN, PAPOLA, PAPOLB, PAPOLG, PAPPA, PAPPA2, PAPSS1, PAPSS2, PAQR3,
PAQR4, PAQR5, PAQR6, PAQR7, PAQR8, PAQR9, PARD3, PARD3B, PARD6A, PARD6B,
PARD6G, PARG, PARK7, PARL, PARM1, PARN, PARP1, PARP10, PARP11, PARP12,
PARP14, PARP15, PARP16, PARP2, PARP3, PARP4, PARP6, PARP8, PARP9, PARPBP,
PARS2, PARVA, PARVB, PARVG, PASD1, PASK, PATE1, PATE2, PATE3, PATE4, PATJ,
PATL1, PATL2, PATZ1, PAWR, PAX1, PAX2, PAX3, PAX4, PAX5, PAX6, PAX7, PAX8,
PAX9, PAXBP1, PAXIP1, PAXX, PBDC1, PBK, PBLD, PBOV1, PBRM1, PBX1, PBX2, PBX3,
PBX4, PBXIP1, PC, PCBD1, PCBD2, PCBP1, PCBP2, PCBP3, PCBP4, PCCA, PCCB, PCDH1,
PCDH10, PCDH11X, PCDH11Y, PCDH12, PCDH15, PCDH17, PCDH18, PCDH19, PCDH20,
PCDH7, PCDH8, PCDH9, PCDHA1, PCDHA10, PCDHA11, PCDHA12, PCDHA13, PCDHA2,
PCDHA3, PCDHA4, PCDHA5, PCDHA6, PCDHA7, PCDHA8, PCDHA9, PCDHAC1,
PCDHAC2, PCDHB1, PCDHB10, PCDHB11, PCDHB12, PCDHB13, PCDHB14, PCDHB15,
PCDHB16, PCDHB2, PCDHB3, PCDHB4, PCDHB5, PCDHB6, PCDHB7, PCDHB8, PCDHB9,
PCDHGA1, PCDHGA10, PCDHGA11, PCDHGA12, PCDHGA2, PCDHGA3, PCDHGA4,
PCDHGA5, PCDHGA6, PCDHGA7, PCDHGA8, PCDHGA9, PCDHGB1, PCDHGB2,
PCDHGB3, PCDHGB4, PCDHGB5, PCDHGB6, PCDHGB7, PCDHGC3, PCDHGC4,
PCDHGC5, PCEDIA, PCEDIB, PCF11, PCGF1, PCGF2, PCGF3, PCGF5, PCGF6, PCID2,
PCIF1, PCK1, PCK2, PCLAF, PCLO, PCM1, PCMT1, PCMTD1, PCMTD2, PCNA, PCNP,
PCNT, PCNX1, PCNX2, PCNX3, PCNX4, PCOLCE, PCOLCE2, PCOTH, PCP2, PCP4,
PCP4L1, PCSK1, PCSKIN, PCSK2, PCSK4, PCSK5, PCSK6, PCSK7, PCSK9, PCTP,
PCYOX1, PCYOX1L, PCYTIA, PCYTIB, PCYT2, PDAP1, PDC, PDCD1, PDCD10, PDCD11,
PDCD1LG2, PDCD2, PDCD2L, PDCD4, PDCD5, PDCD6, PDCD6IP, PDCD7, PDCL, PDCL2,
PDCL3, PDE10A, PDE11A, PDE12, PDEIA, PDEIB, PDEIC, PDE2A, PDE3A, PDE3B,
PDE4A, PDE4B, PDE4C, PDE4D, PDE4DIP, PDESA, PDE6A, PDE6B, PDE6C, PDE6D,
PDE6G, PDE6H, PDE7A, PDE7B, PDE8A, PDE8B, PDE9A, PDF, PDGFA, PDGFB, PDGFC,
PDGFD, PDGFRA, PDGFRB, PDGFRL, PDHA1, PDHA2, PDHB, PDHX, PDIA2, PDIA3,
PDIA4, PDIA5, PDIA6, PDIK1L, PDILT, PDK1, PDK2, PDK3, PDK4, PDLIM1, PDLIM2,
PDLIM3, PDLIM4, PDLIM5, PDLIM7, PDP1, PDP2, PDPK1, PDPN, PDPR, PDRG1, PDS5A,
PDS5B, PDSS1, PDSS2, PDX1, PDXDC1, PDXK, PDXP, PDYN, PDZD11, PDZD2, PDZD3,
PDZD4, PDZD7, PDZD8, PDZD9, PDZK1, PDZKIIP1, PDZRN3, PDZRN4, PEA15, PEAK1,
PEAR1, PEBP1, PEBP4, PECAM1, PECR, PEF1, PEG10, PEG3, PELI1, PELI2, PELI3, PELO,
PELP1, PEMT, PENK, PEPD, PER1, PER2, PER3, PERM1, PERP, PES1, PET100, PET117,
PEX1, PEX10, PEX11A, PEX11B, PEX11G, PEX12, PEX13, PEX14, PEX16, PEX19, PEX2,
PEX26, PEX3, PEX5, PEX5L, PEX6, PEX7, PF4, PF4V1, PFAS, PFDN1, PFDN2, PFDN4,
PFDN5, PFDN6, PFKFB1, PFKFB2, PFKFB3, PFKFB4, PFKL, PFKM, PFKP, PFN1, PFN2,
PFN3, PFN4, PGA3, PGA4, PGA5, PGAM1, PGAM2, PGAM4, PGAM5, PGAP1, PGAP2,
PGAP3, PGBD1, PGBD2, PGBD4, PGBD5, PGC, PGD, PGF, PGGHG, PGGT1B, PGK1, PGK2,
PGLS, PGLYRP1, PGLYRP2, PGLYRP3, PGLYRP4, PGM1, PGM2, PGM2L1, PGM3, PGM5,
PGP, PGPEP1, PGPEP1L, PGR, PGRMC1, PGRMC2, PGS1, PHACTR1, PHACTR2,
PHACTR3, PHACTR4, PHAX, PHB, PHB2, PHC1, PHC2, PHC3, PHEX, PHF1, PHF10,
PHF11, PHF12, PHF13, PHF14, PHF19, PHF2, PHF20, PHF20L1, PHF21A, PHF21B, PHF23,
PHF24, PHF3, PHF5A, PHF6, PHF7, PHF8, PHGDH, PHGR1, PHIP, PHKA1, PHKA2, PHKB,
PHKG1, PHKG2, PHLDA1, PHLDA2, PHLDA3, PHLDB1, PHLDB2, PHLDB3, PHLPP1,
PHLPP2, PHOSPHO1, PHOSPHO2, PHOX2A, PHOX2B, PHPT1, PHRF1, PHTF1, PHTF2,
PHYH, PHYHD1, PHYHIP, PHYHIPL, PHYKPL, PI15, PI16, PI3, PI4K2A, PI4K2B, PI4KA,
PI4KB, PIANP, PIAS1, PIAS2, PIAS3, PIAS4, PIBF1, PICALM, PICK1, PID1, PIDD1, PIEZO1,
PIEZO2, PIF1, PIFO, PIGA, PIGB, PIGBOS1, PIGC, PIGF, PIGG, PIGH, PIGK, PIGL, PIGM,
PIGN, PIGO, PIGP, PIGQ, PIGR, PIGS, PIGT, PIGU, PIGV, PIGW, PIGX, PIGY, PIGZ,
PIH1D1, PIH1D2, PIH1D3, PIK3AP1, PIK3C2A, PIK3C2B, PIK3C2G, PIK3C3, PIK3CA,
PIK3CB, PIK3CD, PIK3CG, PIK3IP1, PIK3R1, PIK3R2, PIK3R3, PIK3R4, PIK3R5, PIK3R6,
PIKFYVE, PILRA, PILRB, PIM1, PIM2, PIM3, PIMREG, PIN1, PIN4, PINK1, PINLYP,
PINX1, PIP, PIP4K2A, PIP4K2B, PIP4K2C, PIP5K1A, PIP5K1B, PIP5K1C, PIP5KL1, PIPOX,
PIR, PIRT, PISD, PITHD1, PITPNA, PITPNB, PITPNC1, PITPNM1, PITPNM2, PITPNM3,
PITRM1, PITX1, PITX2, PITX3, PIWIL1, PIWIL2, PIWIL3, PIWIL4, PJA1, PJA2, PKD1,
PKD1L1, PKD1L2, PKD1L3, PKD2, PKD2L1, PKD2L2, PKDCC, PKDREJ, PKHD1,
PKHD1L1, PKIA, PKIB, PKIG, PKLR, PKM, PKMYT1, PKN1, PKN2, PKN3, PKNOX1,
PKNOX2, PKP1, PKP2, PKP3, PKP4, PLAIA, PLA2G10, PLA2G12A, PLA2G12B, PLA2G15,
PLA2G16, PLA2GIB, PLA2G2A, PLA2G2C, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3,
PLA2G4A, PLA2G4B, PLA2G4C, PLA2G4D, PLA2G4E, PLA2G4F, PLA2G5, PLA2G6,
PLA2G7, PLA2R1, PLAA, PLAC1, PLAC4, PLAC8, PLAC8L1, PLAC9, PLAG1, PLAGL1,
PLAGL2, PLAT, PLAU, PLAUR, PLB1, PLBD1, PLBD2, PLCB1, PLCB2, PLCB3, PLCB4,
PLCD1, PLCD3, PLCD4, PLCE1, PLCG1, PLCG2, PLCH1, PLCH2, PLCL1, PLCL2, PLCXD1,
PLCXD2, PLCXD3, PLCZ1, PLD1, PLD2, PLD3, PLD4, PLD5, PLD6, PLEC, PLEK, PLEK2,
PLEKHA1, PLEKHA2, PLEKHA3, PLEKHA4, PLEKHA5, PLEKHA6, PLEKHA7, PLEKHA8,
PLEKHB1, PLEKHB2, PLEKHD1, PLEKHF1, PLEKHF2, PLEKHG1, PLEKHG2, PLEKHG3,
PLEKHG4, PLEKHG4B, PLEKHG5, PLEKHG6, PLEKHG7, PLEKHH1, PLEKHH2,
PLEKHH3, PLEKHJ1, PLEKHM1, PLEKHM2, PLEKHM3, PLEKHN1, PLEKHO1,
PLEKHO2, PLEKHS1, PLET1, PLG, PLGLB1, PLGLB2, PLGRKT, PLIN1, PLIN2, PLIN3,
PLIN4, PLIN5, PLK1, PLK2, PLK3, PLK4, PLK5, PLLP, PLN, PLOD1, PLOD2, PLOD3, PLP1,
PLP2, PLPBP, PLPP1, PLPP2, PLPP3, PLPP4, PLPP5, PLPP6, PLPP7, PLPPR1, PLPPR2,
PLPPR3, PLPPR4, PLPPR5, PLRG1, PLS1, PLS3, PLSCR1, PLSCR2, PLSCR3, PLSCR4,
PLSCR5, PLTP, PLVAP, PLXDC1, PLXDC2, PLXNA1, PLXNA2, PLXNA3, PLXNA4,
PLXNB1, PLXNB2, PLXNB3, PLXNC1, PLXND1, PM20D1, PM20D2, PMAIP1, PMCH,
PMEL, PMEPA1, PMF1, PMF1-BGLAP, PMFBP1, PML, PMM1, PMM2, PMP2, PMP22,
PMPCA, PMPCB, PMS1, PMS2, PMVK, PNCK, PNISR, PNKD, PNKP, PNLDC1, PNLIP,
PNLIPRP1, PNLIPRP2, PNLIPRP3, PNMA1, PNMA2, PNMA3, PNMA5, PNMA6A, PNMA6E,
PNMA6F, PNMASA, PNMA8B, PNMA8C, PNMT, PNN, PNO1, PNOC, PNP, PNPLA1,
PNPLA2, PNPLA3, PNPLA4, PNPLA5, PNPLA6, PNPLA7, PNPLA8, PNPO, PNPT1, PNRC1,
PNRC2, POCIA, POCIB, POCIB-GALNT4, POC5, PODN, PODNL1, PODXL, PODXL2,
POF1B, POFUT1, POFUT2, POGK, POGLUT1, POGZ, POLA1, POLA2, POLB, POLD1,
POLD2, POLD3, POLD4, POLDIP2, POLDIP3, POLE, POLE2, POLE3, POLE4, POLG,
POLG2, POLH, POLI, POLK, POLL, POLM, POLN, POLQ, POLR1A, POLR1B, POLR1C,
POLR1D, POLR1E, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G,
POLR2H, POLR2I, POLR2J, POLR2J2, POLR2J3, POLR2K, POLR2L, POLR2M, POLR3A,
POLR3B, POLR3C, POLR3D, POLR3E, POLR3F, POLR3G, POLR3GL, POLR3H, POLR3K,
POLRMT, POM121, POM121C, POM121L12, POM121L2, POMC, POMGNT1, POMGNT2,
POMK, POMP, POMT1, POMT2, POMZP3, PON1, PON2, PON3, POP1, POP4, POP5, POP7,
POPDC2, POPDC3, POR, PORCN, POSTN, POT1, POTEA, POTEB, POTEB2, POTEB3,
POTEC, POTED, POTEE, POTEF, POTEG, POTEH, POTEI, POTEJ, POTEM, POU1F1,
POU2AF1, POU2F1, POU2F2, POU2F3, POU3F1, POU3F2, POU3F3, POU3F4, POU4F1,
POU4F2, POU4F3, POU5F1, POU5F1B, POU5F2, POU6F1, POU6F2, PP2D1, PPA1, PPA2,
PPAN, PPAN-P2RY11, PPARA, PPARD, PPARG, PPARGC1A, PPARGC1B, PPAT, PPBP,
PPCDC, PPCS, PPDPF, PPEF1, PPEF2, PPFIA1, PPFIA2, PPFIA3, PPFIA4, PPFIBP1, PPFIBP2,
PPHLN1, PPIA, PPIAL4A, PPIAL4C, PPIAL4D, PPIAL4E, PPIAL4F, PPIAL4G, PPIB, PPIC,
PPID, PPIE, PPIF, PPIG, PPIH, PPIL1, PPIL2, PPIL3, PPIL4, PPIL6, PPIP5K1, PPIP5K2, PPL,
PPM1A, PPM1B, PPM1D, PPM1E, PPM1F, PPM1G, PPM1H, PPM1J, PPM1K, PPM1L,
PPM1M, PPM1N, PPME1, PPOX, PPP1CA, PPP1CB, PPP1CC, PPP1R10, PPP1R11,
PPP1R12A, PPP1R12B, PPP1R12C, PPP1R13B, PPP1R13L, PPP1R14A, PPP1R14B,
PPP1R14C, PPP1R14D, PPP1R15A, PPP1R15B, PPP1R16A, PPP1R16B, PPP1R17, PPP1R18,
PPP1RIA, PPP1R1B, PPP1R1C, PPP1R2, PPP1R21, PPP1R26, PPP1R27, PPP1R2P3,
PPP1R2P9, PPP1R32, PPP1R35, PPP1R36, PPP1R37, PPP1R3A, PPP1R3B, PPP1R3C,
PPP1R3D, PPP1R3E, PPP1R3F, PPP1R3G, PPP1R42, PPP1R7, PPP1R8, PPP1R9A, PPP1R9B,
PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, PPP2R2D,
PPP2R3A, PPP2R3B, PPP2R3C, PPP2R5A, PPP2R5B, PPP2R5C, PPP2R5D, PPP2R5E,
PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PPP4C, PPP4R1, PPP4R2, PPP4R3A, PPP4R3B,
PPP4R3CP, PPP4R4, PPP5C, PPP5D1, PPP6C, PPP6R1, PPP6R2, PPP6R3, PPRC1, PPT1, PPT2,
PPT2-EGFL8, PPTC7, PPWD1, PPY, PQBP1, PQLC1, PQLC2, PQLC2L, PQLC3, PRAC1,
PRAC2, PRADC1, PRAF2, PRAG1, PRAM1, PRAME, PRAMEF1, PRAMEF10, PRAMEF11,
PRAMEF12, PRAMEF13, PRAMEF14, PRAMEF15, PRAMEF17, PRAMEF18, PRAMEF19,
PRAMEF2, PRAMEF20, PRAMEF25, PRAMEF26, PRAMEF27, PRAMEF33, PRAMEF4,
PRAMEF5, PRAMEF6, PRAMEF7, PRAMEF8, PRAMEF9, PRAP1, PRB1, PRB2, PRB3,
PRB4, PRC1, PRCC, PRCD, PRCP, PRDM1, PRDM10, PRDM11, PRDM12, PRDM13,
PRDM14, PRDM15, PRDM16, PRDM2, PRDM4, PRDM5, PRDM6, PRDM7, PRDM8,
PRDM9, PRDX1, PRDX2, PRDX3, PRDX4, PRDX5, PRDX6, PREB, PRELID1, PRELID2,
PRELID3A, PRELID3B, PRELP, PREP, PREPL, PREX1, PREX2, PRF1, PRG2, PRG3, PRG4,
PRH1, PRH2, PRICKLE1, PRICKLE2, PRICKLE3, PRICKLE4, PRIM1, PRIM2, PRIMA1,
PRIMPOL, PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKACA, PRKACB, PRKACG,
PRKAG1, PRKAG2, PRKAG3, PRKARIA, PRKARIB, PRKAR2A, PRKAR2B, PRKCA,
PRKCB, PRKCD, PRKCE, PRKCG, PRKCH, PRKCI, PRKCQ, PRKCSH, PRKCZ, PRKD1,
PRKD2, PRKD3, PRKDC, PRKG1, PRKG2, PRKN, PRKRA, PRKRIP1, PRKX, PRL, PRLH,
PRLHR, PRLR, PRM1, PRM2, PRM3, PRMT1, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7,
PRMT8, PRMT9, PRND, PRNP, PRNT, PROB1, PROC, PROCA1, PROCR, PRODH, PRODH2,
PROK1, PROK2, PROKR1, PROKR2, PROM1, PROM2, PROP1, PRORY, PROS1, PROSER1,
PROSER2, PROSER3, PROX1, PROX2, PROZ, PRPF18, PRPF19, PRPF3, PRPF31, PRPF38A,
PRPF38B, PRPF39, PRPF4, PRPF40A, PRPF40B, PRPF4B, PRPF6, PRPF8, PRPH, PRPH2,
PRPS1, PRPS1L1, PRPS2, PRPSAP1, PRPSAP2, PRR11, PRR12, PRR13, PRR14, PRR14L,
PRR15, PRR15L, PRR16, PRR18, PRR19, PRR20A, PRR20B, PRR20C, PRR20D, PRR20E,
PRR21, PRR22, PRR23A, PRR23B, PRR23C, PRR23D1, PRR23D2, PRR25, PRR26, PRR27,
PRR29, PRR3, PRR30, PRR32, PRR34, PRR35, PRR36, PRR4, PRR5, PRR5-ARHGAP8,
PRR5L, PRR7, PRR9, PRRC1, PRRC2A, PRRC2B, PRRC2C, PRRG1, PRRG2, PRRG3,
PRRG4, PRRT1, PRRT2, PRRT3, PRRT4, PRRX1, PRRX2, PRSS1, PRSS12, PRSS16, PRSS2,
PRSS21, PRSS22, PRSS23, PRSS27, PRSS3, PRSS33, PRSS35, PRSS36, PRSS37, PRSS38,
PRSS41, PRSS42, PRSS45, PRSS46, PRSS48, PRSS50, PRSS51, PRSS53, PRSS54, PRSS55,
PRSS56, PRSS57, PRSS58, PRSS8, PRTFDC1, PRTG, PRTN3, PRUNE1, PRUNE2, PRX, PRY,
PRY2, PSAP, PSAPL1, PSAT1, PSCA, PSD, PSD2, PSD3, PSD4, PSEN1, PSEN2, PSENEN,
PSG1, PSG11, PSG2, PSG3, PSG4, PSG5, PSG6, PSG7, PSG8, PSG9, PSIP1, PSKH1, PSKH2,
PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMA8, PSMB1, PSMB10,
PSMB11, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMB8, PSMB9, PSMC1,
PSMC2, PSMC3, PSMC3IP, PSMC4, PSMC5, PSMC6, PSMD1, PSMD10, PSMD11, PSMD12,
PSMD13, PSMD14, PSMD2, PSMD3, PSMD4, PSMD5, PSMD6, PSMD7, PSMD8, PSMD9,
PSME1, PSME2, PSME3, PSME4, PSMF1, PSMG1, PSMG2, PSMG3, PSMG4, PSORSIC1,
PSORSIC2, PSPC1, PSPH, PSPN, PSRC1, PSTK, PSTPIP1, PSTPIP2, PTAFR, PTAR1, PTBP1,
PTBP2, PTBP3, PTCD1, PTCD2, PTCD3, PTCH1, PTCH2, PTCHD1, PTCHD3, PTCHD4,
PTCRA, PTDSS1, PTDSS2, PTEN, PTER, PTFIA, PTGDR, PTGDR2, PTGDS, PTGER1,
PTGER2, PTGER3, PTGER4, PTGES, PTGES2, PTGES3, PTGES3L, PTGES3L-AARSD1,
PTGFR, PTGFRN, PTGIR, PTGIS, PTGR1, PTGR2, PTGS1, PTGS2, PTH, PTHIR, PTH2,
PTH2R, PTHLH, PTK2, PTK2B, PTK6, PTK7, PTMA, PTMS, PTN, PTOV1, PTP4A1, PTP4A2,
PTP4A3, PTPA, PTPDC1, PTPMT1, PTPN1, PTPN11, PTPN12, PTPN13, PTPN14, PTPN18,
PTPN2, PTPN20, PTPN21, PTPN22, PTPN23, PTPN3, PTPN4, PTPN5, PTPN6, PTPN7,
PTPN9, PTPRA, PTPRB, PTPRC, PTPRCAP, PTPRD, PTPRE, PTPRF, PTPRG, PTPRH,
PTPRJ, PTPRK, PTPRM, PTPRN, PTPRN2, PTPRO, PTPRQ, PTPRR, PTPRS, PTPRT, PTPRU,
PTPRZ1, PTRH1, PTRH2, PTRHD1, PTS, PTTG1, PTTG1IP, PTTG2, PTX3, PTX4, PUDP,
PUF60, PUM1, PUM2, PUM3, PURA, PURB, PURG, PUS1, PUS10, PUS3, PUS7, PUS7L,
PUSL1, PVALB, PVR, PVRIG, PWP1, PWP2, PWWP2A, PWWP2B, PXDC1, PXDN, PXDNL,
PXK, PXMP2, PXMP4, PXN, PXT1, PXYLP1, PYCARD, PYCR1, PYCR2, PYCR3, PYDC1,
PYDC2, PYGB, PYGL, PYGM, PYGO1, PYGO2, PYHIN1, PYM1, PYROXD1, PYROXD2,
PYURF, PYY, PZP, QARS, QDPR, QKI, QPCT, QPCTL, QPRT, QRFP, QRFPR, QRICH1,
QRICH2, QRSL1, QSER1, QSOX1, QSOX2, QTRT1, QTRT2, R3HCC1, R3HCC1L, R3HDM1,
R3HDM2, R3HDM4, R3HDML, RAB10, RAB11A, RAB11B, RAB11FIP1, RAB11FIP2,
RAB11FIP3, RAB11FIP4, RAB11FIP5, RAB12, RAB13, RAB14, RAB15, RAB17, RAB18,
RAB19, RABIA, RABIB, RAB20, RAB21, RAB22A, RAB23, RAB24, RAB25, RAB26,
RAB27A, RAB27B, RAB28, RAB29, RAB2A, RAB2B, RAB30, RAB31, RAB32, RAB33A,
RAB33B, RAB34, RAB35, RAB36, RAB37, RAB38, RAB39A, RAB39B, RAB3A, RAB3B,
RAB3C, RAB3D, RAB3GAP1, RAB3GAP2, RAB3IL1, RAB3IP, RAB40A, RAB40AL,
RAB40B, RAB40C, RAB41, RAB42, RAB43, RAB44, RAB4A, RAB4B, RAB4B-EGLN2,
RAB5A, RAB5B, RAB5C, RAB6A, RAB6B, RAB6C, RAB7A, RAB7B, RAB8A, RAB8B,
RAB9A, RAB9B, RABAC1, RABEP1, RABEP2, RABEPK, RABGAP1, RABGAP1L,
RABGEF1, RABGGTA, RABGGTB, RABIF, RABL2A, RABL2B, RABL3, RABL6, RAC1,
RAC2, RAC3, RACGAP1, RACK1, RAD1, RAD17, RAD18, RAD21, RAD21L1, RAD23A,
RAD23B, RAD50, RAD51, RAD51AP1, RAD51AP2, RAD51B, RAD51C, RAD51D, RAD52,
RAD54B, RAD54L, RAD54L2, RAD9A, RAD9B, RADIL, RAE1, RAETIE, RAETIG,
RAET1L, RAF1, RAG1, RAG2, RAI1, RAI14, RAI2, RALA, RALB, RALBP1, RALGAPA1,
RALGAPA2, RALGAPB, RALGDS, RALGPS1, RALGPS2, RALY, RALYL, RAMP1,
RAMP2, RAMP3, RAN, RANBP1, RANBP10, RANBP17, RANBP2, RANBP3, RANBP3L,
RANBP6, RANBP9, RANGAP1, RANGRF, RAPIA, RAPIB, RAPIGAP, RAPIGAP2,
RAP1GDS1, RAP2A, RAP2B, RAP2C, RAPGEF1, RAPGEF2, RAPGEF3, RAPGEF4,
RAPGEF5, RAPGEF6, RAPGEFL1, RAPH1, RAPSN, RARA, RARB, RARG, RARRES1,
RARRES2, RARRES3, RARS, RARS2, RASA1, RASA2, RASA3, RASA4, RASA4B, RASAL1,
RASAL2, RASAL3, RASD1, RASD2, RASEF, RASGEF1A, RASGEF1B, RASGEF1C,
RASGRF1, RASGRF2, RASGRP1, RASGRP2, RASGRP3, RASGRP4, RASIP1, RASL10A,
RASL10B, RASL11A, RASL11B, RASL12, RASSF1, RASSF10, RASSF2, RASSF3, RASSF4,
RASSF5, RASSF6, RASSF7, RASSF8, RASSF9, RAVER1, RAVER2, RAX, RAX2, RB1,
RB1CC1, RBAK, RBAK-RBAKDN, RBBP4, RBBP5, RBBP6, RBBP7, RBBP8, RBBP8NL,
RBBP9, RBCK1, RBFA, RBFOX1, RBFOX2, RBFOX3, RBKS, RBL1, RBL2, RBM10, RBM11,
RBM12, RBM12B, RBM14, RBM14-RBM4, RBM15, RBM15B, RBM17, RBM18, RBM19,
RBM20, RBM22, RBM23, RBM24, RBM25, RBM26, RBM27, RBM28, RBM3, RBM33,
RBM34, RBM38, RBM39, RBM4, RBM41, RBM42, RBM43, RBM44, RBM45, RBM46,
RBM47, RBM48, RBM4B, RBM5, RBM6, RBM7, RBM8A, RBMS1, RBMS2, RBMS3, RBMX,
RBMX2, RBMXL1, RBMXL2, RBMXL3, RBMY1A1, RBMY1B, RBMYID, RBMYIE,
RBMY1F, RBMY1J, RBP1, RBP2, RBP3, RBP4, RBP5, RBP7, RBPJ, RBPJL, RBPMS,
RBPMS2, RBSN, RBX1, RC3H1, RC3H2, RCAN1, RCAN2, RCAN3, RCBTB1, RCBTB2,
RCC1, RCC1L, RCC2, RCCD1, RCE1, RCHY1, RCL1, RCN1, RCN2, RCN3, RCOR1, RCOR2,
RCOR3, RCSD1, RCVRN, RD3, RD3L, RDH10, RDH11, RDH12, RDH13, RDH14, RDH16,
RDH5, RDH8, RDM1, RDX, REC114, REC8, RECK, RECQL, RECQL4, RECQL5, REEP1,
REEP2, REEP3, REEP4, REEP5, REEP6, REGIA, REGIB, REG3A, REG3G, REG4, REL,
RELA, RELB, RELL1, RELL2, RELN, RELT, REM1, REM2, REN, RENBP, REP15, REPIN1,
REPS1, REPS2, RER1, RERE, RERG, RERGL, RESP18, REST, RET, RETN, RETNLB,
RETREG1, RETREG2, RETREG3, RETSAT, REV1, REV3L, REXO1, REXO2, REXO4,
REX05, RFC1, RFC2, RFC3, RFC4, RFC5, RFESD, RFFL, RFK, RFLNA, RFLNB, RFNG,
RFPL1, RFPL2, RFPL3, RFPL3S, RFPL4A, RFPL4AL1, RFPL4B, RFT1, RFTN1, RFTN2,
RFWD2, RFWD3, RFX1, RFX2, RFX3, RFX4, RFX5, RFX6, RFX7, RFX8, RFXANK, RFXAP,
RGCC, RGL1, RGL2, RGL3, RGL4, RGMA, RGMB, RGN, RGP1, RGPD1, RGPD2, RGPD3,
RGPD4, RGPD5, RGPD6, RGPD8, RGR, RGS1, RGS10, RGS11, RGS12, RGS13, RGS14,
RGS16, RGS17, RGS18, RGS19, RGS2, RGS20, RGS21, RGS22, RGS3, RGS4, RGS5, RGS6,
RGS7, RGS7BP, RGS8, RGS9, RGS9BP, RGSL1, RHAG, RHBDD1, RHBDD2, RHBDD3,
RHBDF1, RHBDF2, RHBDL1, RHBDL2, RHBDL3, RHBG, RHCE, RHCG, RHD, RHEB,
RHEBL1, RHNO1, RHO, RHOA, RHOB, RHOBTB1, RHOBTB2, RHOBTB3, RHOC, RHOD,
RHOF, RHOG, RHOH, RHOJ, RHOQ, RHOT1, RHOT2, RHOU, RHOV, RHOXF1, RHOXF2,
RHOXF2B, RHPN1, RHPN2, RIBC1, RIBC2, RIC1, RIC3, RIC8A, RIC8B, RICTOR, RIDA,
RIF1, RIIAD1, RILP, RILPL1, RILPL2, RIMBP2, RIMBP3, RIMBP3B, RIMBP3C, RIMKLA,
RIMKLB, RIMS1, RIMS2, RIMS3, RIMS4, RIN1, RIN2, RIN3, RING1, RINL, RINT1, RIOK1,
RIOK2, RIOK3, RIOX1, RIOX2, RIPK1, RIPK2, RIPK3, RIPK4, RIPOR1, RIPOR2, RIPOR3,
RIPPLY1, RIPPLY2, RIPPLY3, RIT1, RIT2, RITA1, RLBP1, RLF, RLIM, RLN1, RLN2, RLN3,
RMDN1, RMDN2, RMDN3, RMI1, RMI2, RMND1, RMND5A, RMND5B, RNASE1,
RNASE10, RNASE11, RNASE12, RNASE13, RNASE2, RNASE3, RNASE4, RNASE6,
RNASE7, RNASE8, RNASE9, RNASEH1, RNASEH2A, RNASEH2B, RNASEH2C, RNASEK,
RNASEK-C17orf49, RNASEL, RNASET2, RND1, RND2, RND3, RNF10, RNF103, RNF103-
CHMP3, RNF11, RNF111, RNF112, RNF113A, RNF113B, RNF114, RNF115, RNF121,
RNF122, RNF123, RNF125, RNF126, RNF128, RNF13, RNF130, RNF133, RNF135, RNF138,
RNF139, RNF14, RNF141, RNF144A, RNF144B, RNF145, RNF146, RNF148, RNF149,
RNF150, RNF151, RNF152, RNF157, RNF165, RNF166, RNF167, RNF168, RNF169, RNF17,
RNF170, RNF175, RNF180, RNF181, RNF182, RNF183, RNF185, RNF186, RNF187, RNF19A,
RNF19B, RNF2, RNF20, RNF207, RNF208, RNF212, RNF212B, RNF213, RNF214, RNF215,
RNF216, RNF217, RNF219, RNF220, RNF222, RNF223, RNF224, RNF225, RNF24, RNF25,
RNF26, RNF31, RNF32, RNF34, RNF38, RNF39, RNF4, RNF40, RNF41, RNF43, RNF44,
RNF5, RNF6, RNF7, RNF8, RNFT1, RNFT2, RNGTT, RNH1, RNLS, RNMT, RNPC3, RNPEP,
RNPEPL1, RNPS1, ROBO1, ROBO2, ROBO3, ROBO4, ROCK1, ROCK2, ROGD1, ROM1,
ROMO1, ROPN1, ROPN1B, ROPN1L, ROR1, ROR2, RORA, RORB, RORC, ROS1, RP1,
RP1L1, RP2, RP9, RPA1, RPA2, RPA3, RPA4, RPAIN, RPAP1, RPAP2, RPAP3, RPE, RPE65,
RPEL1, RPF1, RPF2, RPGR, RPGRIP1, RPGRIP1L, RPH3A, RPH3AL, RPIA, RPL10, RPL10A,
RPL10L, RPL11, RPL12, RPL13, RPL13A, RPL14, RPL15, RPL17, RPL17-C18orf32, RPL18,
RPL18A, RPL19, RPL21, RPL22, RPL22L1, RPL23, RPL23A, RPL24, RPL26, RPL26L1,
RPL27, RPL27A, RPL28, RPL29, RPL3, RPL30, RPL31, RPL32, RPL34, RPL35, RPL35A,
RPL36, RPL36A, RPL36A-HNRNPH2, RPL36AL, RPL37, RPL37A, RPL38, RPL39, RPL39L,
RPL3L, RPL4, RPL41, RPL5, RPL6, RPL7, RPL7A, RPL7L1, RPL8, RPL9, RPLPO, RPLP1,
RPLP2, RPN1, RPN2, RPP14, RPP21, RPP25, RPP25L, RPP30, RPP38, RPP40, RPRDIA,
RPRD1B, RPRD2, RPRM, RPRML, RPS10, RPS10-NUDT3, RPS11, RPS12, RPS13, RPS14,
RPS15, RPS15A, RPS16, RPS17, RPS18, RPS19, RPS19BP1, RPS2, RPS20, RPS21, RPS23,
RPS24, RPS25, RPS26, RPS27, RPS27A, RPS27L, RPS28, RPS29, RPS3, RPS3A, RPS4X,
RPS4Y1, RPS4Y2, RPS5, RPS6, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA4, RPS6KA5,
RPS6KA6, RPS6KB1, RPS6KB2, RPS6KC1, RPS6KL1, RPS7, RPS8, RPS9, RPSA, RPTN,
RPTOR, RPUSD1, RPUSD2, RPUSD3, RPUSD4, RRAD, RRAGA, RRAGB, RRAGC, RRAGD,
RRAS, RRAS2, RRBP1, RREB1, RRH, RRM1, RRM2, RRM2B, RRN3, RRNAD1, RRP1,
RRP12, RRP15, RRP1B, RRP36, RRP7A, RRP8, RRP9, RRS1, RS1, RSAD1, RSAD2, RSBN1,
RSBN1L, RSCIA1, RSF1, RSG1, RSLID1, RSL24D1, RSPH1, RSPH10B, RSPH10B2,
RSPH14, RSPH3, RSPH4A, RSPH6A, RSPH9, RSPO1, RSPO2, RSPO3, RSPO4, RSPRY1,
RSRC1, RSRC2, RSRP1, RSU1, RTBDN, RTCA, RTCB, RTEL1, RTEL1-TNFRSF6B, RTF1,
RTFDC1, RTKN, RTKN2, RTL1, RTL10, RTL3, RTL4, RTL5, RTL6, RTL8A, RTL8B, RTL8C,
RTL9, RTN1, RTN2, RTN3, RTN4, RTN4IP1, RTN4R, RTN4RL1, RTN4RL2, RTP1, RTP2,
RTP3, RTP4, RTP5, RTTN, RUBCN, RUBCNL, RUFY1, RUFY2, RUFY3, RUFY4, RUNDC1,
RUNDC3A, RUNDC3B, RUNX1, RUNXIT1, RUNX2, RUNX3, RUSC1, RUSC2, RUVBL1,
RUVBL2, RWDD1, RWDD2A, RWDD2B, RWDD3, RWDD4, RXFP1, RXFP2, RXFP3,
RXFP4, RXRA, RXRB, RXRG, RYBP, RYK, RYR1, RYR2, RYR3, S100A1, S100A10,
S100A11, S100A12, S100A13, S100A14, S100A16, S100A2, S100A3, S100A4, S100A5,
S100A6, S100A7, S100A7A, S100A7L2, S100A8, S100A9, S100B, S100G, S100P, S100PBP,
S100Z, SIPR1, SIPR2, SIPR3, SIPR4, SIPR5, SAA1, SAA2, SAA2-SAA4, SAA4, SAAL1,
SAC3D1, SACM1L, SACS, SAE1, SAFB, SAFB2, SAG, SAGE1, SALL1, SALL2, SALL3,
SALL4, SAMD1, SAMD10, SAMD11, SAMD12, SAMD13, SAMD14, SAMD15, SAMD3,
SAMD4A, SAMD4B, SAMD5, SAMD7, SAMD8, SAMD9, SAMD9L, SAMHD1, SAMM50,
SAMSN1, SAP130, SAP18, SAP25, SAP30, SAP30BP, SAP30L, SAPCD1, SAPCD2, SAR1A,
SAR1B, SARAF, SARDH, SARM1, SARNP, SARS, SARS2, SART1, SART3, SASH1, SASH3,
SASS6, SAT1, SAT2, SATB1, SATB2, SATL1, SAV1, SAXO1, SAXO2, SAYSD1, SBDS,
SBF1, SBF2, SBK1, SBK2, SBK3, SBNO1, SBNO2, SBSN, SBSPON, SC5D, SCAF1, SCAF11,
SCAF4, SCAF8, SCA1, SCAMP1, SCAMP2, SCAMP3, SCAMP4, SCAMP5, SCAND1, SCAP,
SCAPER, SCARA3, SCARA5, SCARB1, SCARB2, SCARF1, SCARF2, SCART1, SCCPDH,
SCD, SCD5, SCEL, SCFD1, SCFD2, SCG2, SCG3, SCG5, SCGB1A1, SCGB1C1, SCGB1C2,
SCGB1D1, SCGB1D2, SCGB1D4, SCGB2A1, SCGB2A2, SCGB2B2, SCGB3A1, SCGB3A2,
SCGN, SCHIP1, SCIMP, SCIN, SCLT1, SCLY, SCMH1, SCML1, SCML2, SCML4, SCN10A,
SCN11A, SCNIA, SCNIB, SCN2A, SCN2B, SCN3A, SCN3B, SCN4A, SCN4B, SCN5A,
SCN7A, SCN8A, SCN9A, SCNM1, SCNN1A, SCNN1B, SCNN1D, SCNN1G, SCO1, SCO2,
SCOC, SCP2, SCP2D1, SCPEP1, SCRG1, SCRIB, SCRN1, SCRN2, SCRN3, SCRT1, SCRT2,
SCT, SCTR, SCUBE1, SCUBE2, SCUBE3, SCX, SCYL1, SCYL2, SCYL3, SDAD1, SDC1,
SDC2, SDC3, SDC4, SDCBP, SDCBP2, SDCCAG3, SDCCAG8, SDE2, SDF2, SDF2L1, SDF4,
SDHA, SDHAF1, SDHAF2, SDHAF3, SDHAF4, SDHB, SDHC, SDHD, SDK1, SDK2,
SDR16C5, SDR39U1, SDR42E1, SDR42E2, SDR9C7, SDS, SDSL, SEBOX, SEC11A, SEC11C,
SEC13, SEC14L1, SEC14L2, SEC14L3, SEC14L4, SEC14L5, SEC14L6, SEC16A, SEC16B,
SEC22A, SEC22B, SEC22C, SEC23A, SEC23B, SEC23IP, SEC24A, SEC24B, SEC24C,
SEC24D, SEC31A, SEC31B, SEC61A1, SEC61A2, SEC61B, SEC61G, SEC62, SEC63,
SECISBP2, SECISBP2L, SECTM1, SEH1L, SEL1L, SEL1L2, SEL1L3, SELE, SELENBP1,
SELENOF, SELENOH, SELENOI, SELENOK, SELENOM, SELENON, SELENOO,
SELENOP, SELENOS, SELENOT, SELENOV, SELENOW, SELL, SELP, SELPLG, SEM1,
SEMA3A, SEMA3B, SEMA3C, SEMA3D, SEMA3E, SEMA3F, SEMA3G, SEMA4A,
SEMA4B, SEMA4C, SEMA4D, SEMA4F, SEMA4G, SEMASA, SEMA5B, SEMA6A,
SEMA6B, SEMA6C, SEMA6D, SEMA7A, SEMG1, SEMG2, SENP1, SENP2, SENP3, SENP3-
EIF4A1, SENP5, SENP6, SENP7, SENP8, SEPHS1, SEPHS2, SEPSECS, SEPT1, SEPT10,
SEPT11, SEPT12, SEPT14, SEPT2, SEPT3, SEPT4, SEPT5, SEPT6, SEPT7, SEPT8, SEPT9,
SERAC1, SERBP1, SERF1A, SERF1B, SERF2, SERGEF, SERHL2, SERINC1, SERINC2,
SERINC3, SERINC4, SERINC5, SERP1, SERP2, SERPINA1, SERPINA10, SERPINA11,
SERPINA12, SERPINA2, SERPINA3, SERPINA4, SERPINA5, SERPINA6, SERPINA7,
SERPINA9, SERPINB1, SERPINB10, SERPINB11, SERPINB12, SERPINB13, SERPINB2,
SERPINB3, SERPINB4, SERPINB5, SERPINB6, SERPINB7, SERPINB8, SERPINB9,
SERPINC1, SERPIND1, SERPINE1, SERPINE2, SERPINE3, SERPINF1, SERPINF2,
SERPING1, SERPINH1, SERPINI1, SERPINI2, SERTAD1, SERTAD2, SERTAD3, SERTAD4,
SERTM1, SESN1, SESN2, SESN3, SESTD1, SET, SETBP1, SETD1A, SETD1B, SETD2,
SETD3, SETD4, SETD5, SETD6, SETD7, SETD9, SETDB1, SETDB2, SETMAR, SETSIP,
SETX, SEZ6, SEZ6L, SEZ6L2, SF1, SF3A1, SF3A2, SF3A3, SF3B1, SF3B2, SF3B3, SF3B4,
SF3B5, SF3B6, SFI1, SFMBT1, SFMBT2, SFN, SFPQ, SFR1, SFRP1, SFRP2, SFRP4, SFRP5,
SFSWAP, SFT2D1, SFT2D2, SFT2D3, SFTA2, SFTA3, SFTPA1, SFTPA2, SFTPB, SFTPC,
SFTPD, SFXN1, SFXN2, SFXN3, SFXN4, SFXN5, SGCA, SGCB, SGCD, SGCE, SGCG,
SGCZ, SGF29, SGIP1, SGK1, SGK2, SGK3, SGK494, SGMS1, SGMS2, SGO1, SGO2, SGPL1,
SGPP1, SGPP2, SGSH, SGSM1, SGSM2, SGSM3, SGTA, SGTB, SH2B1, SH2B2, SH2B3,
SH2DIA, SH2D1B, SH2D2A, SH2D3A, SH2D3C, SH2D4A, SH2D4B, SH2D5, SH2D6,
SH2D7, SH3BGR, SH3BGRL, SH3BGRL2, SH3BGRL3, SH3BP1, SH3BP2, SH3BP4, SH3BP5,
SH3BP5L, SH3D19, SH3D21, SH3GL1, SH3GL2, SH3GL3, SH3GLB1, SH3GLB2, SH3KBP1,
SH3PXD2A, SH3PXD2B, SH3RF1, SH3RF2, SH3RF3, SH3TC1, SH3TC2, SH3YL1, SHANK1,
SHANK2, SHANK3, SHARPIN, SHB, SHBG, SHC1, SHC2, SHC3, SHC4, SHCBP1,
SHCBP1L, SHD, SHE, SHF, SHH, SHISA2, SHISA3, SHISA4, SHISA5, SHISA6, SHISA7,
SHISA8, SHISA9, SHKBP1, SHMT1, SHMT2, SHOC2, SHOX, SHOX2, SHPK, SHPRH,
SHQ1, SHROOM1, SHROOM2, SHROOM3, SHROOM4, SHTN1, SI, SIAE, SIAH1, SIAH2,
SIAH3, SIDT1, SIDT2, SIGIRR, SIGLEC1, SIGLEC10, SIGLEC11, SIGLEC12, SIGLEC14,
SIGLEC15, SIGLEC5, SIGLEC6, SIGLEC7, SIGLEC8, SIGLEC9, SIGLECL1, SIGMAR1,
SIK1, SIK2, SIK3, SIKE1, SIL1, SIM1, SIM2, SIMC1, SIN3A, SIN3B, SIPA1, SIPA1L1,
SIPA1L2, SIPA1L3, SIRPA, SIRPB1, SIRPB2, SIRPD, SIRPG, SIRT1, SIRT2, SIRT3, SIRT4,
SIRT5, SIRT6, SIRT7, SIT1, SIVA1, SIX1, SIX2, SIX3, SIX4, SIX5, SIX6, SKA1, SKA2, SKA3,
SKAP1, SKAP2, SKI, SKIDA1, SKIL, SKIV2L, SKIV2L2, SKOR1, SKOR2, SKP1, SKP2, SLA,
SLA2, SLAIN1, SLAIN2, SLAMF1, SLAMF6, SLAMF7, SLAMF8, SLAMF9, SLBP,
SLC10A1, SLC10A2, SLC10A3, SLC10A4, SLC10A5, SLC10A6, SLC10A7, SLC11A1,
SLC11A2, SLC12A1, SLC12A2, SLC12A3, SLC12A4, SLC12A5, SLC12A6, SLC12A7,
SLC12A8, SLC12A9, SLC13A1, SLC13A2, SLC13A3, SLC13A4, SLC13A5, SLC14A1,
SLC14A2, SLC15A1, SLC15A2, SLC15A3, SLC15A4, SLC15A5, SLC16A1, SLC16A10,
SLC16A11, SLC16A12, SLC16A13, SLC16A14, SLC16A2, SLC16A3, SLC16A4, SLC16A5,
SLC16A6, SLC16A7, SLC16A8, SLC16A9, SLC17A1, SLC17A2, SLC17A3, SLC17A4,
SLC17A5, SLC17A6, SLC17A7, SLC17A8, SLC17A9, SLC18A1, SLC18A2, SLC18A3,
SLC18B1, SLC19A1, SLC19A2, SLC19A3, SLC1A1, SLC1A2, SLC1A3, SLC1A4, SLC1A5,
SLC1A6, SLC1A7, SLC20A1, SLC20A2, SLC22A1, SLC22A10, SLC22A11, SLC22A12,
SLC22A13, SLC22A14, SLC22A15, SLC22A16, SLC22A17, SLC22A18, SLC22A18AS,
SLC22A2, SLC22A23, SLC22A24, SLC22A25, SLC22A3, SLC22A31, SLC22A4, SLC22A5,
SLC22A6, SLC22A7, SLC22A8, SLC22A9, SLC23A1, SLC23A2, SLC23A3, SLC24A1,
SLC24A2, SLC24A3, SLC24A4, SLC24A5, SLC25A1, SLC25A10, SLC25A11, SLC25A12,
SLC25A13, SLC25A14, SLC25A15, SLC25A16, SLC25A17, SLC25A18, SLC25A19,
SLC25A2, SLC25A20, SLC25A21, SLC25A22, SLC25A23, SLC25A24, SLC25A25,
SLC25A26, SLC25A27, SLC25A28, SLC25A29, SLC25A3, SLC25A30, SLC25A31,
SLC25A32, SLC25A33, SLC25A34, SLC25A35, SLC25A36, SLC25A37, SLC25A38,
SLC25A39, SLC25A4, SLC25A40, SLC25A41, SLC25A42, SLC25A43, SLC25A44,
SLC25A45, SLC25A46, SLC25A47, SLC25A48, SLC25A5, SLC25A51, SLC25A52,
SLC25A53, SLC25A6, SLC26A1, SLC26A10, SLC26A11, SLC26A2, SLC26A3, SLC26A4,
SLC26A5, SLC26A6, SLC26A7, SLC26A8, SLC26A9, SLC27A1, SLC27A2, SLC27A3,
SLC27A4, SLC27A5, SLC27A6, SLC28A1, SLC28A2, SLC28A3, SLC29A1, SLC29A2,
SLC29A3, SLC29A4, SLC2A1, SLC2A10, SLC2A11, SLC2A12, SLC2A13, SLC2A14,
SLC2A2, SLC2A3, SLC2A4, SLC2A4RG, SLC2A5, SLC2A6, SLC2A7, SLC2A8, SLC2A9,
SLC30A1, SLC30A10, SLC30A2, SLC30A3, SLC30A4, SLC30A5, SLC30A6, SLC30A7,
SLC30A8, SLC30A9, SLC31A1, SLC31A2, SLC32A1, SLC33A1, SLC34A1, SLC34A2,
SLC34A3, SLC35A1, SLC35A2, SLC35A3, SLC35A4, SLC35A5, SLC35B1, SLC35B2,
SLC35B3, SLC35B4, SLC35C1, SLC35C2, SLC35D1, SLC35D2, SLC35D3, SLC35E1,
SLC35E2, SLC35E2B, SLC35E3, SLC35E4, SLC35F1, SLC35F2, SLC35F3, SLC35F4,
SLC35F5, SLC35F6, SLC35G1, SLC35G2, SLC35G3, SLC35G4, SLC35G5, SLC35G6,
SLC36A1, SLC36A2, SLC36A3, SLC36A4, SLC37A1, SLC37A2, SLC37A3, SLC37A4,
SLC38A1, SLC38A10, SLC38A11, SLC38A2, SLC38A3, SLC38A4, SLC38A5, SLC38A6,
SLC38A7, SLC38A8, SLC38A9, SLC39A1, SLC39A10, SLC39A11, SLC39A12, SLC39A13,
SLC39A14, SLC39A2, SLC39A3, SLC39A4, SLC39A5, SLC39A6, SLC39A7, SLC39A8,
SLC39A9, SLC3A1, SLC3A2, SLC40A1, SLC41A1, SLC41A2, SLC41A3, SLC43A1,
SLC43A2, SLC43A3, SLC44A1, SLC44A2, SLC44A3, SLC44A4, SLC44A5, SLC45A1,
SLC45A2, SLC45A3, SLC45A4, SLC46A1, SLC46A2, SLC46A3, SLC47A1, SLC47A2,
SLC48A1, SLC4A1, SLC4A10, SLC4A11, SLC4A1AP, SLC4A2, SLC4A3, SLC4A4, SLC4A5,
SLC4A7, SLC4A8, SLC4A9, SLC50A1, SLC51A, SLC51B, SLC52A1, SLC52A2, SLC52A3,
SLC5A1, SLC5A10, SLC5A11, SLC5A12, SLC5A2, SLC5A3, SLC5A4, SLC5A5, SLC5A6,
SLC5A7, SLC5A8, SLC5A9, SLC6A1, SLC6A11, SLC6A12, SLC6A13, SLC6A14, SLC6A15,
SLC6A16, SLC6A17, SLC6A18, SLC6A19, SLC6A2, SLC6A20, SLC6A3, SLC6A4, SLC6A5,
SLC6A6, SLC6A7, SLC6A8, SLC6A9, SLC7A1, SLC7A10, SLC7A11, SLC7A13, SLC7A14,
SLC7A2, SLC7A3, SLC7A4, SLC7A5, SLC7A6, SLC7A6OS, SLC7A7, SLC7A8, SLC7A9,
SLC8A1, SLC8A2, SLC8A3, SLC8B1, SLC9A1, SLC9A2, SLC9A3, SLC9A3R1, SLC9A3R2,
SLC9A4, SLC9A5, SLC9A6, SLC9A7, SLC9A8, SLC9A9, SLC9B1, SLC9B2, SLC9C1,
SLC9C2, SLCO1A2, SLCO1B1, SLCO1B3, SLCO1B7, SLCO1C1, SLCO2A1, SLCO2B1,
SLCO3A1, SLCO4A1, SLCO4C1, SLCO5A1, SLCO6A1, SLF1, SLF2, SLFN11, SLFN12,
SLFN12L, SLFN13, SLFN14, SLFN5, SLFNL1, SLIRP, SLIT1, SLIT2, SLIT3, SLITRK1,
SLITRK2, SLITRK3, SLITRK4, SLITRK5, SLITRK6, SLK, SLMAP, SLN, SLP1, SLTM, SLU7,
SLURP1, SLURP2, SLXIA, SLXIB, SLX4, SLX4IP, SMAD1, SMAD2, SMAD3, SMAD4,
SMAD5, SMAD6, SMAD7, SMAD9, SMAGP, SMAP1, SMAP2, SMARCA1, SMARCA2,
SMARCA4, SMARCA5, SMARCAD1, SMARCAL1, SMARCB1, SMARCC1, SMARCC2,
SMARCD1, SMARCD2, SMARCD3, SMARCE1, SMCIA, SMC1B, SMC2, SMC3, SMC4,
SMC5, SMC6, SMCHD1, SMCO1, SMCO2, SMCO3, SMCO4, SMCP, SMCR8, SMDT1,
SMG1, SMG5, SMG6, SMG7, SMG8, SMG9, SMIM1, SMIM10, SMIM10L1, SMIM10L2A,
SMIM10L2B, SMIM11A, SMIM11B, SMIM12, SMIM13, SMIM14, SMIM15, SMIM17,
SMIM18, SMIM19, SMIM2, SMIM20, SMIM21, SMIM22, SMIM23, SMIM24, SMIM26,
SMIM27, SMIM28, SMIM29, SMIM3, SMIM30, SMIM31, SMIM4, SMIM5, SMIM6, SMIM7,
SMIM8, SMIM9, SMKR1, SMLR1, SMN1, SMN2, SMNDC1, SMO, SMOC1, SMOC2, SMOX,
SMPD1, SMPD2, SMPD3, SMPD4, SMPDL3A, SMPDL3B, SMPX, SMR3A, SMR3B, SMS,
SMTN, SMTNL1, SMTNL2, SMU1, SMUG1, SMURF1, SMURF2, SMYD1, SMYD2, SMYD3,
SMYD4, SMYD5, SNAI1, SNAI2, SNAI3, SNAP23, SNAP25, SNAP29, SNAP47, SNAP91,
SNAPC1, SNAPC2, SNAPC3, SNAPC4, SNAPC5, SNAPIN, SNCA, SNCAIP, SNCB, SNCG,
SND1, SNED1, SNF8, SNHG28, SNIP1, SNN, SNPH, SNRK, SNRNP200, SNRNP25,
SNRNP27, SNRNP35, SNRNP40, SNRNP48, SNRNP70, SNRPA, SNRPA1, SNRPB, SNRPB2,
SNRPC, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, SNRPN, SNTA1, SNTB1,
SNTB2, SNTG1, SNTG2, SNTN, SNU13, SNUPN, SNURF, SNW1, SNX1, SNX10, SNX11,
SNX12, SNX13, SNX14, SNX15, SNX16, SNX17, SNX18, SNX19, SNX2, SNX20, SNX21,
SNX22, SNX24, SNX25, SNX27, SNX29, SNX3, SNX30, SNX31, SNX32, SNX33, SNX4,
SNX5, SNX6, SNX7, SNX8, SNX9, SOAT1, SOAT2, SOBP, SOCS1, SOCS2, SOCS3, SOCS4,
SOCS5, SOCS6, SOCS7, SOD1, SOD2, SOD3, SOGA1, SOGA3, SOHLH1, SOHLH2, SON,
SORBS1, SORBS2, SORBS3, SORCS1, SORCS2, SORCS3, SORD, SORL1, SORT1, SOS1,
SOS2, SOST, SOSTDC1, SOWAHA, SOWAHB, SOWAHC, SOWAHD, SOX1, SOX10,
SOX11, SOX12, SOX13, SOX14, SOX15, SOX17, SOX18, SOX2, SOX21, SOX3, SOX30,
SOX4, SOX5, SOX6, SOX7, SOX8, SOX9, SP1, SP100, SP110, SP140, SP140L, SP2, SP3, SP4,
SP5, SP6, SP7, SP8, SP9, SPA17, SPAAR, SPACA1, SPACA3, SPACA4, SPACA5, SPACA5B,
SPACA6, SPACA7, SPACA9, SPAG1, SPAG11A, SPAG11B, SPAG16, SPAG17, SPAG4,
SPAG5, SPAG6, SPAG7, SPAG8, SPAG9, SPAM1, SPANXA1, SPANXA2, SPANXB1,
SPANXC, SPANXD, SPANXN1, SPANXN2, SPANXN3, SPANXN4, SPANXN5, SPARC,
SPARCL1, SPART, SPAST, SPATA1, SPATA12, SPATA13, SPATA16, SPATA17, SPATA18,
SPATA19, SPATA2, SPATA20, SPATA21, SPATA22, SPATA24, SPATA25, SPATA2L,
SPATA3, SPATA31A1, SPATA31A3, SPATA31A5, SPATA31A6, SPATA31A7, SPATA31D1,
SPATA31D3, SPATA31D4, SPATA31E1, SPATA32, SPATA33, SPATA4, SPATA45,
SPATA46, SPATA5, SPATA5L1, SPATA6, SPATA6L, SPATA7, SPATA8, SPATA9, SPATC1,
SPATC1L, SPATS1, SPATS2, SPATS2L, SPC24, SPC25, SPCS1, SPCS2, SPCS3, SPDEF,
SPDL1, SPDYA, SPDYC, SPDYE1, SPDYE16, SPDYE2, SPDYE2B, SPDYE3, SPDYE4,
SPDYE5, SPDYE6, SPECC1, SPECC1L, SPECC1L-ADORA2A, SPEF1, SPEF2, SPEG,
SPEM1, SPEN, SPERT, SPESP1, SPG11, SPG21, SPG7, SPHAR, SPHK1, SPHK2, SPHKAP,
SPI1, SPIB, SPIC, SPICE1, SPIDR, SPIN1, SPIN2A, SPIN2B, SPIN3, SPIN4, SPINK1,
SPINK13, SPINK14, SPINK2, SPINK4, SPINK5, SPINK6, SPINK7, SPINK8, SPINK9, SPINT1,
SPINT2, SPINT3, SPINT4, SPIRE1, SPIRE2, SPN, SPNS1, SPNS2, SPNS3, SPO11, SPOCD1,
SPOCK1, SPOCK2, SPOCK3, SPON1, SPON2, SPOP, SPOPL, SPOUT1, SPP1, SPP2, SPPL2A,
SPPL2B, SPPL2C, SPPL3, SPR, SPRED1, SPRED2, SPRED3, SPRN, SPRRIA, SPRRIB,
SPRR2A, SPRR2B, SPRR2D, SPRR2E, SPRR2F, SPRR2G, SPRR3, SPRR4, SPRR5, SPRTN,
SPRY1, SPRY2, SPRY3, SPRY4, SPRYD3, SPRYD4, SPRYD7, SPSB1, SPSB2, SPSB3,
SPSB4, SPTA1, SPTAN1, SPTB, SPTBN1, SPTBN2, SPTBN4, SPTBN5, SPTLC1, SPTLC2,
SPTLC3, SPTSSA, SPTSSB, SPTY2D1, SPTY2D1-AS1, SPX, SPZ1, SQLE, SQOR, SQSTM1,
SRA1, SRBD1, SRC, SRCAP, SRCIN1, SRD5A1, SRD5A2, SRD5A3, SREBF1, SREBF2,
SREK1, SREK1IP1, SRF, SRFBP1, SRGAP1, SRGAP2, SRGAP2B, SRGAP2C, SRGAP3,
SRGN, SRI, SRL, SRM, SRMS, SRP14, SRP19, SRP54, SRP68, SRP72, SRP9, SRPK1, SRPK2,
SRPK3, SRPRA, SRPRB, SRPX, SRPX2, SRR, SRRD, SRRM1, SRRM2, SRRM3, SRRM4,
SRRM5, SRRT, SRSF1, SRSF10, SRSF11, SRSF12, SRSF2, SRSF3, SRSF4, SRSF5, SRSF6,
SRSF7, SRSF8, SRSF9, SRXN1, SRY, SS18, SS18L1, SS18L2, SSB, SSBP1, SSBP2, SSBP3,
SSBP4, SSC4D, SSC5D, SSFA2, SSH1, SSH2, SSH3, SSMEM1, SSNA1, SSPN, SSPO, SSR1,
SSR2, SSR3, SSR4, SSRP1, SSSCA1, SST, SSTR1, SSTR2, SSTR3, SSTR4, SSTR5, SSU72,
SSU72P8, SSUH2, SSX1, SSX2, SSX2B, SSX2IP, SSX3, SSX4, SSX4B, SSX5, SSX7, ST13,
ST14, ST18, ST20, ST20-MTHFS, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4, ST3GAL5,
ST3GAL6, ST5, ST6GAL1, ST6GAL2, ST6GALNAC1, ST6GALNAC2, ST6GALNAC3,
ST6GALNAC4, ST6GALNAC5, ST6GALNAC6, ST7, ST7L, ST8SIA1, ST8SIA2, ST8SIA3,
ST8SIA4, ST8SIA5, ST8SIA6, STAB1, STAB2, STAC, STAC2, STAC3, STAG1, STAG2,
STAG3, STAM, STAM2, STAMBP, STAMBPL1, STAP1, STAP2, STAR, STARD10,
STARD13, STARD3, STARD3NL, STARD4, STARD5, STARD6, STARD7, STARD8,
STARD9, STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6, STATH, STAU1,
STAU2, STBD1, STC1, STC2, STEAP1, STEAPIB, STEAP2, STEAP3, STEAP4, STH, STIL,
STIM1, STIM2, STIP1, STK10, STK11, STK11IP, STK16, STK17A, STK17B, STK19, STK24,
STK25, STK26, STK3, STK31, STK32A, STK32B, STK32C, STK33, STK35, STK36, STK38,
STK38L, STK39, STK4, STK40, STKLD1, STMN1, STMN2, STMN3, STMN4, STMND1,
STN1, STOM, STOML1, STOML2, STOML3, STON1, STON1-GTF2A1L, STON2, STOX1,
STOX2, STPG1, STPG2, STPG3, STPG4, STRA6, STRA8, STRADA, STRADB, STRAP,
STRBP, STRC, STRIP1, STRIP2, STRN, STRN3, STRN4, STS, STT3A, STT3B, STUB1,
STUM, STX10, STX11, STX12, STX16, STX16-NPEPL1, STX17, STX18, STX19, STX1A,
STX1B, STX2, STX3, STX4, STX5, STX6, STX7, STX8, STXBP1, STXBP2, STXBP3,
STXBP4, STXBP5, STXBP5L, STXBP6, STYK1, STYX, STYXL1, SUB1, SUCLA2, SUCLG1,
SUCLG2, SUCNR1, SUCO, SUDS3, SUFU, SUGCT, SUGP1, SUGP2, SUGT1, SULF1, SULF2,
SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULTIB1, SULTIC2, SULT1C3, SULTIC4,
SULT1E1, SULT2A1, SULT2B1, SULT4A1, SULT6B1, SUMF1, SUMF2, SUMO1, SUMO2,
SUMO3, SUMO4, SUN1, SUN2, SUN3, SUN5, SUOX, SUPT16H, SUPT20H, SUPT3H,
SUPT4H1, SUPT5H, SUPT6H, SUPT7L, SUPV3L1, SURF1, SURF2, SURF4, SURF6, SUSD1,
SUSD2, SUSD3, SUSD4, SUSD5, SUSD6, SUV39H1, SUV39H2, SUZ12, SV2A, SV2B, SV2C,
SVBP, SVEP1, SVIL, SVIP, SVOP, SVOPL, SWAP70, SWI5, SWSAP1, SWT1, SYAP1, SYBU,
SYCE1, SYCE1L, SYCE2, SYCE3, SYCN, SYCP1, SYCP2, SYCP2L, SYCP3, SYDE1, SYDE2,
SYF2, SYK, SYMPK, SYN1, SYN2, SYN3, SYNC, SYNCRIP, SYNDIG1, SYNDIG1L,
SYNE1, SYNE2, SYNE3, SYNE4, SYNGAP1, SYNGR1, SYNGR2, SYNGR3, SYNGR4,
SYNJ1, SYNJ2, SYNJ2BP, SYNJ2BP-COX16, SYNM, SYNPO, SYNPO2, SYNPO2L, SYNPR,
SYNRG, SYP, SYPL1, SYPL2, SYS1, SYS1-DBNDD2, SYT1, SYT10, SYT11, SYT12, SYT13,
SYT14, SYT15, SYT16, SYT17, SYT2, SYT3, SYT4, SYT5, SYT6, SYT7, SYT8, SYT9,
SYTL1, SYTL2, SYTL3, SYTL4, SYTL5, SYVN1, SZRD1, SZT2, T, TAAR1, TAAR2, TAAR5,
TAAR6, TAAR8, TAAR9, TAB1, TAB2, TAB3, TAC1, TAC3, TAC4, TACC1, TACC2,
TACC3, TACO1, TACR1, TACR2, TACR3, TACSTD2, TADA1, TADA2A, TADA2B, TADA3,
TAF1, TAF10, TAF11, TAF12, TAF13, TAF15, TAF1A, TAF1B, TAF1C, TAF1D, TAF1L,
TAF2, TAF3, TAF4, TAF4B, TAF5, TAF5L, TAF6, TAF6L, TAF7, TAF7L, TAF8, TAF9,
TAF9B, TAGAP, TAGLN, TAGLN2, TAGLN3, TAL1, TAL2, TALDO1, TAMM41, TANC1,
TANC2, TANGO2, TANGO6, TANK, TAOK1, TAOK2, TAOK3, TAP1, TAP2, TAPBP,
TAPBPL, TAPT1, TARBP1, TARBP2, TARDBP, TARM1, TARS, TARS2, TARSL2, TASIR1,
TAS1R2, TASIR3, TAS2R1, TAS2R10, TAS2R13, TAS2R14, TAS2R16, TAS2R19, TAS2R20,
TAS2R3, TAS2R30, TAS2R31, TAS2R38, TAS2R39, TAS2R4, TAS2R40, TAS2R41,
TAS2R42, TAS2R43, TAS2R46, TAS2R5, TAS2R50, TAS2R60, TAS2R7, TAS2R8, TAS2R9,
TASP1, TAT, TATDN1, TATDN2, TATDN3, TAXIBP1, TAXIBP3, TAZ, TBATA, TBC1D1,
TBC1D10A, TBC1D10B, TBC1D10C, TBC1D12, TBC1D13, TBC1D14, TBC1D15, TBC1D16,
TBC1D17, TBC1D19, TBC1D2, TBC1D20, TBC1D21, TBC1D22A, TBC1D22B, TBC1D23,
TBC1D24, TBC1D25, TBC1D26, TBC1D28, TBC1D29, TBC1D2B, TBC1D3, TBC1D30,
TBC1D31, TBC1D32, TBC1D3B, TBC1D3C, TBC1D3D, TBC1D3E, TBC1D3F, TBC1D3G,
TBC1D3H, TBC1D3I, TBC1D3K, TBC1D3L, TBC1D4, TBC1D5, TBC1D7, TBC1D8,
TBC1D8B, TBC1D9, TBC1D9B, TBCA, TBCB, TBCC, TBCCD1, TBCD, TBCE, TBCEL,
TBCK, TBK1, TBKBP1, TBLIX, TBL1XR1, TBL1Y, TBL2, TBL3, TBP, TBPL1, TBPL2,
TBR1, TBRG1, TBRG4, TBX1, TBX10, TBX15, TBX18, TBX19, TBX2, TBX20, TBX21,
TBX22, TBX3, TBX4, TBX5, TBX6, TBXA2R, TBXAS1, TC2N, TCAF1, TCAF2, TCAIM,
TCAP, TCEA1, TCEA2, TCEA3, TCEAL1, TCEAL2, TCEAL3, TCEAL4, TCEAL5, TCEAL6,
TCEAL7, TCEAL8, TCEAL9, TCEANC, TCEANC2, TCERG1, TCERG1L, TCF12, TCF15,
TCF19, TCF20, TCF21, TCF23, TCF24, TCF25, TCF3, TCF4, TCF7, TCF7L1, TCF7L2, TCFL5,
TCHH, TCHHL1, TCHP, TCIRG1, TCLIA, TCL1B, TCN1, TCN2, TCOF1, TCP1, TCP10,
TCP10L, TCP10L2, TCP11, TCP11L1, TCP11L2, TCP11X2, TCTA, TCTE1, TCTE3,
TCTEX1D1, TCTEX1D2, TCTEX1D4, TCTN1, TCTN2, TCTN3, TDG, TDGF1, TDO2, TDP1,
TDP2, TDRD1, TDRD10, TDRD12, TDRD15, TDRD3, TDRD5, TDRD6, TDRD7, TDRD9,
TDRKH, TDRP, TEAD1, TEAD2, TEAD3, TEAD4, TEC, TECPR1, TECPR2, TECR, TECRL,
TECTA, TECTB, TEDDM1, TEF, TEFM, TEK, TEKT1, TEKT2, TEKT3, TEKT4, TEKT5,
TELO2, TEN1, TEN1-CDK3, TENM1, TENM2, TENM3, TENM4, TEP1, TEPP, TEPSIN,
TERB1, TERB2, TERF1, TERF2, TERF2IP, TERT, TES, TESC, TESK1, TESK2, TESMIN,
TESPA1, TET1, TET2, TET3, TEX10, TEX101, TEX11, TEX12, TEX13A, TEX13B, TEX13C,
TEX13D, TEX14, TEX15, TEX19, TEX2, TEX22, TEX26, TEX261, TEX264, TEX28, TEX29,
TEX30, TEX33, TEX35, TEX36, TEX37, TEX38, TEX43, TEX44, TEX45, TEX46, TEX47,
TEX48, TEX49, TEX50, TEX51, TEX9, TF, TFAM, TFAP2A, TFAP2B, TFAP2C, TFAP2D,
TFAP2E, TFAP4, TFBIM, TFB2M, TFCP2, TFCP2L1, TFDP1, TFDP2, TFDP3, TFE3, TFEB,
TFEC, TFF1, TFF2, TFF3, TFG, TFIP11, TFPI, TFPI2, TFPT, TFR2, TFRC, TG, TGDS, TGFA,
TGFB1, TGFB1I1, TGFB2, TGFB3, TGFB1, TGFBR1, TGFBR2, TGFBR3, TGFBR3L,
TGFBRAP1, TGIF1, TGIF2, TGIF2-C20orf24, TGIF2LX, TGIF2LY, TGM1, TGM2, TGM3,
TGM4, TGM5, TGM6, TGM7, TGOLN2, TGS1, TH, THADA, THAP1, THAP10, THAP11,
THAP12, THAP2, THAP3, THAP4, THAP5, THAP6, THAP7, THAP8, THAP9, THBD, THBS1,
THBS2, THBS3, THBS4, THEG, THEGL, THEM4, THEM5, THEM6, THEMIS, THEMIS2,
THG1L, THNSL1, THNSL2, THOC1, THOC2, THOC3, THOC5, THOC6, THOC7, THOP1,
THPO, THRA, THRAP3, THRB, THRSP, THSD1, THSD4, THSD7A, THSD7B, THTPA,
THUMPD1, THUMPD2, THUMPD3, THY1, THYN1, TIA1, TIAF1, TIAL1, TIAM1, TIAM2,
TICAM1, TICAM2, TICRR, TIE1, TIFA, TIFAB, TIGAR, TIGD1, TIGD2, TIGD3, TIGD4,
TIGD5, TIGD6, TIGD7, TIGIT, TIMD4, TIMELESS, TIMM10, TIMM10B, TIMM13,
TIMM17A, TIMM17B, TIMM21, TIMM22, TIMM23, TIMM23B, TIMM29, TIMM44,
TIMM50, TIMM8A, TIMM8B, TIMM9, TIMMDC1, TIMP1, TIMP2, TIMP3, TIMP4, TINAG,
TINAGL1, TINCR, TINF2, TIPARP, TIPIN, TIPRL, TIRAP, TISP43, TJAP1, TJP1, TJP2, TJP3,
TK1, TK2, TKFC, TKT, TKTL1, TKTL2, TLCD1, TLCD2, TLDC1, TLDC2, TLE1, TLE2,
TLE3, TLE4, TLE6, TLK1, TLK2, TLL1, TLL2, TLN1, TLN2, TLNRD1, TLR1, TLR10, TLR2,
TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLX1, TLX2, TLX3, TM2D1, TM2D2,
TM2D3, TM4SF1, TM4SF18, TM4SF19, TM4SF19-TCTEX1D2, TM4SF20, TM4SF4,
TM4SF5, TM6SF1, TM6SF2, TM7SF2, TM7SF3, TM9SF1, TM9SF2, TM9SF3, TM9SF4,
TMA16, TMA7, TMBIM1, TMBIM4, TMBIM6, TMC1, TMC2, TMC3, TMC4, TMC5, TMC6,
TMC7, TMC8, TMCC1, TMCC2, TMCC3, TMCO1, TMCO2, TMCO3, TMC04, TMCOSA,
TMC06, TMED1, TMED10, TMED2, TMED3, TMED4, TMED5, TMED6, TMED7, TMED7-
TICAM2, TMED8, TMED9, TMEFF1, TMEFF2, TMEM100, TMEM101, TMEM102,
TMEM104, TMEM105, TMEM106A, TMEM106B, TMEM106C, TMEM107, TMEM108,
TMEM109, TMEM11, TMEM110, TMEM110-MUSTN1, TMEM114, TMEM115, TMEM116,
TMEM117, TMEM119, TMEM120A, TMEM120B, TMEM121, TMEM121B, TMEM123,
TMEM125, TMEM126A, TMEM126B, TMEM127, TMEM128, TMEM129, TMEM130,
TMEM131, TMEM131L, TMEM132A, TMEM132B, TMEM132C, TMEM132D, TMEM132E,
TMEM133, TMEM134, TMEM135, TMEM136, TMEM138, TMEM139, TMEM140,
TMEM141, TMEM143, TMEM144, TMEM145, TMEM147, TMEM14A, TMEM14B,
TMEM14C, TMEM150A, TMEM150B, TMEM150C, TMEM151A, TMEM151B, TMEM154,
TMEM155, TMEM156, TMEM158, TMEM159, TMEM160, TMEM161A, TMEM161B,
TMEM163, TMEM164, TMEM165, TMEM167A, TMEM167B, TMEM168, TMEM169,
TMEM17, TMEM170A, TMEM170B, TMEM171, TMEM173, TMEM174, TMEM175,
TMEM176A, TMEM176B, TMEM177, TMEM178A, TMEM178B, TMEM179, TMEM179B,
TMEM18, TMEM181, TMEM182, TMEM183A, TMEM184A, TMEM184B, TMEM184C,
TMEM185A, TMEM185B, TMEM186, TMEM187, TMEM189, TMEM189-UBE2V1,
TMEM19, TMEM190, TMEM191B, TMEM191C, TMEM192, TMEM196, TMEM198,
TMEM199, TMEM2, TMEM200A, TMEM200B, TMEM200C, TMEM201, TMEM202,
TMEM203, TMEM204, TMEM205, TMEM206, TMEM207, TMEM208, TMEM209,
TMEM210, TMEM211, TMEM212, TMEM213, TMEM214, TMEM215, TMEM216,
TMEM217, TMEM218, TMEM219, TMEM220, TMEM221, TMEM222, TMEM223,
TMEM225, TMEM225B, TMEM229A, TMEM229B, TMEM230, TMEM231, TMEM232,
TMEM233, TMEM234, TMEM235, TMEM236, TMEM237, TMEM238, TMEM239,
TMEM240, TMEM241, TMEM242, TMEM243, TMEM244, TMEM245, TMEM246,
TMEM247, TMEM248, TMEM249, TMEM25, TMEM250, TMEM251, TMEM252, TMEM253,
TMEM254, TMEM255A, TMEM255B, TMEM256, TMEM256-PLSCR3, TMEM257,
TMEM258, TMEM259, TMEM26, TMEM260, TMEM262, TMEM263, TMEM265, TMEM266,
TMEM267, TMEM268, TMEM269, TMEM27, TMEM270, TMEM30A, TMEM30B, TMEM31,
TMEM33, TMEM35A, TMEM35B, TMEM37, TMEM38A, TMEM38B, TMEM39A,
TMEM39B, TMEM40, TMEM41A, TMEM41B, TMEM42, TMEM43, TMEM44, TMEM45A,
TMEM45B, TMEM47, TMEM5, TMEM50A, TMEM50B, TMEM51, TMEM52, TMEM52B,
TMEM53, TMEM54, TMEM55A, TMEM55B, TMEM56, TMEM56-RWDD3, TMEM57,
TMEM59, TMEM59L, TMEM60, TMEM61, TMEM62, TMEM63A, TMEM63B, TMEM63C,
TMEM64, TMEM65, TMEM67, TMEM68, TMEM69, TMEM70, TMEM71, TMEM72,
TMEM74, TMEM74B, TMEM78, TMEM79, TMEM80, TMEM81, TMEM82, TMEM86A,
TMEM86B, TMEM87A, TMEM87B, TMEM88, TMEM88B, TMEM89, TMEM8A, TMEM8B,
TMEM9, TMEM91, TMEM92, TMEM94, TMEM95, TMEM97, TMEM98, TMEM99,
TMEM9B, TMF1, TMIE, TMIGD1, TMIGD2, TMIGD3, TMLHE, TMOD1, TMOD2, TMOD3,
TMOD4, TMPO, TMPPE, TMPRSS11A, TMPRSS11B, TMPRSS11D, TMPRSS11E,
TMPRSS11F, TMPRSS12, TMPRSS13, TMPRSS15, TMPRSS2, TMPRSS3, TMPRSS4,
TMPRSS4-AS1, TMPRSS5, TMPRSS6, TMPRSS7, TMPRSS9, TMSB10, TMSB15A,
TMSB15B, TMSB4X, TMSB4Y, TMTC1, TMTC2, TMTC3, TMTC4, TMUB1, TMUB2,
TMX1, TMX2, TMX2-CTNND1, TMX3, TMX4, TNC, TNF, TNFAIP1, TNFAIP2, TNFAIP3,
TNFAIP6, TNFAIP8, TNFAIP8L1, TNFAIP8L2, TNFAIP8L3, TNFRSF10A, TNFRSF10B,
TNFRSF10C, TNFRSF10D, TNFRSF11A, TNFRSF11B, TNFRSF12A, TNFRSF13B,
TNFRSF13C, TNFRSF14, TNFRSF17, TNFRSF18, TNFRSF19, TNFRSFIA, TNFRSF1B,
TNFRSF21, TNFRSF25, TNFRSF4, TNFRSF6B, TNFRSF8, TNFRSF9, TNFSF10, TNFSF11,
TNFSF12, TNFSF12-TNFSF13, TNFSF13, TNFSF13B, TNFSF14, TNFSF15, TNFSF18,
TNFSF4, TNFSF8, TNFSF9, TNIK, TNIP1, TNIP2, TNIP3, TNK1, TNK2, TNKS, TNKS1BP1,
TNKS2, TNMD, TNN, TNNC1, TNNC2, TNNI1, TNNI2, TNNI3, TNNI3K, TNNT1, TNNT2,
TNNT3, TNP1, TNP2, TNPO1, TNPO2, TNPO3, TNR, TNRC18, TNRC6A, TNRC6B,
TNRC6C, TNS1, TNS2, TNS3, TNS4, TNXB, TOB1, TOB2, TOE1, TOGARAM1,
TOGARAM2, TOLLIP, TOM1, TOM1L1, TOM1L2, TOMM20, TOMM20L, TOMM22,
TOMM34, TOMM40, TOMM40L, TOMM5, TOMM6, TOMM7, TOMM70, TONSL, TOP1,
TOP1MT, TOP2A, TOP2B, TOP3A, TOP3B, TOPAZ1, TOPBP1, TOPORS, TORIA,
TOR1AIP1, TOR1AIP2, TOR1B, TOR2A, TOR3A, TOR4A, TOX, TOX2, TOX3, TOX4, TP53,
TP53AIP1, TP53BP1, TP53BP2, TP53I11, TP53I13, TP5313, TP53INP1, TP53INP2, TP53RK,
TP53TG3, TP53TG3B, TP53TG3C, TP53TG3D, TP53TG3E, TP53TG3F, TP53TG5, TP63,
TP73, TPBG, TPBGL, TPCN1, TPCN2, TPD52, TPD52L1, TPD52L2, TPD52L3, TPGS1,
TPGS2, TPH1, TPH2, TPI1, TPK1, TPM1, TPM2, TPM3, TPM4, TPMT, TPO, TPP1, TPP2,
TPPP, TPPP2, TPPP3, TPR, TPRA1, TPRG1, TPRG1L, TPRKB, TPRN, TPRX1, TPSAB1,
TPSB2, TPSD1, TPSG1, TPST1, TPST2, TPT1, TPTE, TPTE2, TPX2, TRA2A, TRA2B,
TRABD, TRABD2A, TRABD2B, TRAC, TRADD, TRAF1, TRAF2, TRAF3, TRAF3IP1,
TRAF3IP2, TRAF3IP3, TRAF4, TRAF5, TRAF6, TRAF7, TRAFD1, TRAIP, TRAJ1, TRAJ10,
TRAJ11, TRAJ12, TRAJ13, TRAJ14, TRAJ16, TRAJ17, TRAJ18, TRAJ19, TRAJ2, TRAJ20,
TRAJ21, TRAJ22, TRAJ23, TRAJ24, TRAJ25, TRAJ26, TRAJ27, TRAJ28, TRAJ29, TRAJ3,
TRAJ30, TRAJ31, TRAJ32, TRAJ33, TRAJ34, TRAJ35, TRAJ36, TRAJ37, TRAJ38, TRAJ39,
TRAJ4, TRAJ40, TRAJ41, TRAJ42, TRAJ43, TRAJ44, TRAJ45, TRAJ46, TRAJ47, TRAJ48,
TRAJ49, TRAJ5, TRAJ50, TRAJ52, TRAJ53, TRAJ54, TRAJ56, TRAJ57, TRAJ58, TRAJ59,
TRAJ6, TRAJ61, TRAJ7, TRAJ9, TRAK1, TRAK2, TRAM1, TRAM1L1, TRAM2, TRANK1,
TRAP1, TRAPPC1, TRAPPC10, TRAPPC11, TRAPPC12, TRAPPC13, TRAPPC2, TRAPPC2L,
TRAPPC3, TRAPPC3L, TRAPPC4, TRAPPC5, TRAPPC6A, TRAPPC6B, TRAPPC8,
TRAPPC9, TRAT1, TRAV10, TRAV1-1, TRAV1-2, TRAV12-1, TRAV12-2, TRAV12-3,
TRAV13-1, TRAV13-2, TRAV14DV4, TRAV16, TRAV17, TRAV18, TRAV19, TRAV2,
TRAV20, TRAV21, TRAV22, TRAV23DV6, TRAV24, TRAV25, TRAV26-1, TRAV26-2,
TRAV27, TRAV29DV5, TRAV3, TRAV30, TRAV34, TRAV36DV7, TRAV38-1, TRAV38-
2DV8, TRAV39, TRAV4, TRAV40, TRAV41, TRAV5, TRAV6, TRAV7, TRAV8-1, TRAV8-
2, TRAV8-3, TRAV8-4, TRAV8-6, TRAV8-7, TRAV9-1, TRAV9-2, TRBC2, TRBJ2-1, TRBJ2-
2, TRBJ2-2P, TRBJ2-3, TRBJ2-4, TRBJ2-5, TRBJ2-6, TRBJ2-7, TRBV10-1, TRBV10-2,
TRBV10-3, TRBV11-1, TRBV19, TRBV2, TRBV20-1, TRBV20OR9-2, TRBV21OR9-2,
TRBV23-1, TRBV23OR9-2, TRBV24-1, TRBV25-1, TRBV27, TRBV28, TRBV29-1, TRBV30,
TRBV3-1, TRBV4-1, TRBV4-2, TRBV5-1, TRBV5-3, TRBV5-4, TRBV5-5, TRBV5-6, TRBV5-
7, TRBV6-1, TRBV6-4, TRBV6-5, TRBV6-6, TRBV6-7, TRBV6-8, TRBV7-1, TRBV7-3,
TRBV7-4, TRBV7-6, TRBV7-7, TRBV7-9, TRBV9, TRDC, TRDD1, TRDD2, TRDD3, TRDJ1,
TRDJ2, TRDJ3, TRDJ4, TRDMT1, TRDN, TRDV1, TRDV2, TRDV3, TREH, TREM1, TREM2,
TREML1, TREML2, TREML4, TRERF1, TREX1, TREX2, TRGC1, TRGC2, TRGJ1, TRGJ2,
TRGJP, TRGJP1, TRGJP2, TRGV1, TRGV10, TRGV11, TRGV2, TRGV3, TRGV4, TRGV5,
TRGV8, TRGV9, TRH, TRHDE, TRHR, TRIAP1, TRIB1, TRIB2, TRIB3, TRIL, TRIM10,
TRIM11, TRIM13, TRIM14, TRIM15, TRIM16, TRIM16L, TRIM17, TRIM2, TRIM21,
TRIM22, TRIM23, TRIM24, TRIM25, TRIM26, TRIM27, TRIM28, TRIM29, TRIM3, TRIM31,
TRIM32, TRIM33, TRIM34, TRIM35, TRIM36, TRIM37, TRIM38, TRIM39, TRIM39-RPP21,
TRIM4, TRIM40, TRIM41, TRIM42, TRIM43, TRIM43B, TRIM44, TRIM45, TRIM46,
TRIM47, TRIM48, TRIM49, TRIM49B, TRIM49C, TRIM49D1, TRIM49D2, TRIM5, TRIM50,
TRIM51, TRIM52, TRIM54, TRIM55, TRIM56, TRIM58, TRIM59, TRIM6, TRIM60, TRIM61,
TRIM62, TRIM63, TRIM64, TRIM64B, TRIM64C, TRIM65, TRIM66, TRIM67, TRIM68,
TRIM69, TRIM6-TRIM34, TRIM7, TRIM71, TRIM72, TRIM73, TRIM74, TRIM75P, TRIM77,
TRIM8, TRIM9, TRIML1, TRIML2, TRIO, TRIOBP, TRIP10, TRIP11, TRIP12, TRIP13,
TRIP4, TRIP6, TRIQK, TRIR, TRIT1, TRMO, TRMT1, TRMT10A, TRMT10B, TRMT10C,
TRMT11, TRMT112, TRMT12, TRMT13, TRMT1L, TRMT2A, TRMT2B, TRMT44, TRMT5,
TRMT6, TRMT61A, TRMT61B, TRMU, TRNAUIAP, TRNP1, TRNT1, TRO, TROAP,
TROVE2, TRPA1, TRPC1, TRPC3, TRPC4, TRPC4AP, TRPC5, TRPC5OS, TRPC6, TRPC7,
TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPS1, TRPT1,
TRPV1, TRPV2, TRPV3, TRPV4, TRPV5, TRPV6, TRRAP, TRUB1, TRUB2, TSACC, TSC1,
TSC2, TSC22D1, TSC22D2, TSC22D3, TSC22D4, TSEN15, TSEN2, TSEN34, TSEN54, TSFM,
TSG101, TSGA10, TSGA10IP, TSGA13, TSHB, TSHR, TSHZ1, TSHZ2, TSHZ3, TSKS, TSKU,
TSLP, TSN, TSNARE1, TSNAX, TSNAX-DISC1, TSNAXIP1, TSPAN1, TSPAN10, TSPAN11,
TSPAN12, TSPAN13, TSPAN14, TSPAN15, TSPAN16, TSPAN17, TSPAN18, TSPAN19,
TSPAN2, TSPAN3, TSPAN31, TSPAN32, TSPAN33, TSPAN4, TSPAN5, TSPAN6, TSPAN7,
TSPAN8, TSPAN9, TSPEAR, TSPO, TSPO2, TSPOAP1, TSPY1, TSPY10, TSPY2, TSPY3,
TSPY4, TSPY8, TSPYL1, TSPYL2, TSPYL4, TSPYL5, TSPYL6, TSR1, TSR2, TSR3, TSSC4,
TSSKIB, TSSK2, TSSK3, TSSK4, TSSK6, TST, TSTA3, TSTD1, TSTD2, TSTD3, TTBK1,
TTBK2, TTC1, TTC12, TTC13, TTC14, TTC16, TTC17, TTC19, TTC21A, TTC21B, TTC22,
TTC23, TTC23L, TTC24, TTC25, TTC26, TTC27, TTC28, TTC29, TTC3, TTC30A, TTC30B,
TTC31, TTC32, TTC33, TTC34, TTC36, TTC37, TTC38, TTC39A, TTC39B, TTC39C, TTC4,
TTC5, TTC6, TTC7A, TTC7B, TTC8, TTC9, TTC9B, TTC9C, TTF1, TTF2, TTI1, TTI2, TTK,
TTL, TTLL1, TTLL10, TTLL11, TTLL12, TTLL13P, TTLL2, TTLL3, TTLL4, TTLL5, TTLL6,
TTLL7, TTLL8, TTLL9, TTN, TTPA, TTPAL, TTR, TTYH1, TTYH2, TTYH3, TUB, TUBAIA,
TUBA1B, TUBAIC, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA4B, TUBA8, TUBAL3,
TUBB, TUBB1, TUBB2A, TUBB2B, TUBB3, TUBB4A, TUBB4B, TUBB6, TUBB8, TUBD1,
TUBE1, TUBG1, TUBG2, TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5, TUBGCP6, TUFM,
TUFT1, TULP1, TULP2, TULP3, TULP4, TUNAR, TUSC1, TUSC2, TUSC3, TUSC5, TUT1,
TVP23A, TVP23B, TVP23C, TVP23C-CDRT4, TWF1, TWF2, TWIST1, TWIST2, TWISTNB,
TWNK, TWSG1, TXK, TXLNA, TXLNB, TXLNG, TXN, TXN2, TXNDC11, TXNDC12,
TXNDC15, TXNDC16, TXNDC17, TXNDC2, TXNDC5, TXNDC8, TXNDC9, TXNIP, TXNL1,
TXNL4A, TXNL4B, TXNRD1, TXNRD2, TXNRD3, TXNRD3NB, TYK2, TYMP, TYMS,
TYR, TYRO3, TYROBP, TYRP1, TYSND1, TYW1, TYWIB, TYW3, TYW5, U2AF1,
U2AF1L4, U2AF1L5, U2AF2, U2SURP, UACA, UAP1, UAP1L1, UBA1, UBA2, UBA3, UBA5,
UBA52, UBA6, UBA7, UBAC1, UBAC2, UBALD1, UBALD2, UBAP1, UBAP1L, UBAP2,
UBAP2L, UBASH3A, UBASH3B, UBB, UBC, UBD, UBE2A, UBE2B, UBE2C, UBE2D1,
UBE2D2, UBE2D3, UBE2D4, UBE2E1, UBE2E2, UBE2E3, UBE2F, UBE2F-SCLY, UBE2G1,
UBE2G2, UBE2H, UBE2I, UBE2J1, UBE2J2, UBE2K, UBE2L3, UBE2L5P, UBE2L6, UBE2M,
UBE2N, UBE2NL, UBE20, UBE2Q1, UBE2Q2, UBE2Q2L, UBE2QL1, UBE2R2, UBE2S,
UBE2T, UBE2U, UBE2V1, UBE2V2, UBE2W, UBE2Z, UBE3A, UBE3B, UBE3C, UBE3D,
UBE4A, UBE4B, UBFD1, UBIAD1, UBL3, UBL4A, UBL4B, UBL5, UBL7, UBLCP1, UBN1,
UBN2, UBOX5, UBP1, UBQLN1, UBQLN2, UBQLN3, UBQLN4, UBQLNL, UBR1, UBR2,
UBR3, UBR4, UBR5, UBR7, UBTD1, UBTD2, UBTF, UBTFL1, UBXN1, UBXN10, UBXN11,
UBXN2A, UBXN2B, UBXN4, UBXN6, UBXN7, UBXN8, UCHL1, UCHL3, UCHL5, UCK1,
UCK2, UCKL1, UCMA, UCN, UCN2, UCN3, UCP1, UCP2, UCP3, UEVLD, UFC1, UFD1,
UFL1, UFM1, UFSP1, UFSP2, UGCG, UGDH, UGGT1, UGGT2, UGP2, UGT1A1, UGT1A10,
UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A2,
UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7,
UGT3A1, UGT3A2, UGT8, UHMK1, UHRF1, UHRF1BP1, UHRF1BP1L, UHRF2, UIMC1,
ULBP1, ULBP2, ULBP3, ULK1, ULK2, ULK3, ULK4, UMAD1, UMOD, UMODL1, UMPS,
UNC119, UNC119B, UNC13A, UNC13B, UNC13C, UNC13D, UNC45A, UNC45B, UNC50,
UNC5A, UNC5B, UNC5C, UNC5CL, UNC5D, UNC79, UNC80, UNC93A, UNC93B1, UNCX,
UNG, UNK, UNKL, UPB1, UPF1, UPF2, UPF3A, UPF3B, UPKIA, UPKIB, UPK2, UPK3A,
UPK3B, UPK3BL1, UPP1, UPP2, UPRT, UQCC1, UQCC2, UQCC3, UQCR10, UQCR11,
UQCRB, UQCRC1, UQCRC2, UQCRFS1, UQCRH, UQCRHL, UQCRQ, URAD, URB1, URB2,
URGCP, URGCP-MRPS24, URI1, URM1, UROC1, UROD, UROS, USB1, USE1, USF1, USF2,
USF3, USHIC, USHIG, USH2A, USHBP1, USMG5, USO1, USP1, USP10, USP11, USP12,
USP13, USP14, USP15, USP16, USP17L1, USP17L10, USP17L11, USP17L12, USP17L13,
USP17L15, USP17L17, USP17L18, USP17L19, USP17L2, USP17L20, USP17L21, USP17L22,
USP17L23, USP17L24, USP17L25, USP17L26, USP17L27, USP17L28, USP17L29, USP17L3,
USP17L30, USP17L4, USP17L5, USP17L7, USP17L8, USP18, USP19, USP2, USP20, USP21,
USP22, USP24, USP25, USP26, USP27X, USP28, USP29, USP3, USP30, USP31, USP32,
USP33, USP34, USP35, USP36, USP37, USP38, USP39, USP4, USP40, USP41, USP42, USP43,
USP44, USP45, USP46, USP47, USP48, USP49, USP5, USP50, USP51, USP53, USP54, USP6,
USP6NL, USP7, USP8, USP9X, USP9Y, USPL1, UST, UTF1, UTP11, UTP14A, UTP14C,
UTP15, UTP18, UTP20, UTP23, UTP3, UTP4, UTP6, UTRN, UTS2, UTS2B, UTS2R, UTY,
UVRAG, UVSSA, UXS1, UXT, VAC14, VAMP1, VAMP2, VAMP3, VAMP4, VAMP5,
VAMP7, VAMP8, VANGL1, VANGL2, VAPA, VAPB, VARS, VARS2, VASH1, VASH2,
VASN, VASP, VAT1, VAT1L, VAV1, VAV2, VAV3, VAX1, VAX2, VBP1, VCAM1, VCAN,
VCL, VCP, VCPIP1, VCPKMT, VCX, VCX2, VCX3A, VCX3B, VCY, VCY1B, VDAC1,
VDAC2, VDAC3, VDR, VEGFA, VEGFB, VEGFC, VEGFD, VENTX, VEPH1, VEZF1, VEZT,
VGF, VGLL1, VGLL2, VGLL3, VGLL4, VHL, VHLL, VIL1, VILL, VIM, VIP, VIPAS39,
VIPR1, VIPR2, VIRMA, VIT, VKORC1, VKORC1L1, VLDLR, VMA21, VMAC, VMO1,
VMP1, VNIR1, VNIR2, VNIR4, VNIR5, VNN1, VNN2, VNN3, VOPP1, VPREB1, VPREB3,
VPS11, VPS13A, VPS13B, VPS13C, VPS13D, VPS16, VPS18, VPS25, VPS26A, VPS26B,
VPS28, VPS29, VPS33A, VPS33B, VPS35, VPS36, VPS37A, VPS37B, VPS37C, VPS37D,
VPS39, VPS41, VPS45, VPS4A, VPS4B, VPS50, VPS51, VPS52, VPS53, VPS54, VPS72, VPS8,
VPS9D1, VRK1, VRK2, VRK3, VRTN, VSIG1, VSIG10, VSIG10L, VSIG10L2, VSIG2, VSIG4,
VSIG8, VSIR, VSNL1, VSTM1, VSTM2A, VSTM2B, VSTM2L, VSTM4, VSTM5, VSX1,
VSX2, VTA1, VTCN1, VTI1A, VTI1B, VTN, VWA1, VWA2, VWA3A, VWA3B, VWA5A,
VWA5B1, VWA5B2, VWA7, VWA8, VWC2, VWC2L, VWCE, VWDE, VWF, WAC, WAPL,
WARS, WARS2, WAS, WASF1, WASF2, WASF3, WASHC1, WASHC2A, WASHC2C,
WASHC3, WASHC4, WASHC5, WASL, WBP1, WBP11, WBP1L, WBP2, WBP2NL, WBP4,
WDCP, WDFY1, WDFY2, WDFY3, WDFY4, WDHD1, WDPCP, WDR1, WDR11, WDR12,
WDR13, WDR17, WDR18, WDR19, WDR20, WDR24, WDR25, WDR26, WDR27, WDR3,
WDR31, WDR33, WDR34, WDR35, WDR36, WDR37, WDR38, WDR4, WDR41, WDR43,
WDR44, WDR45, WDR45B, WDR46, WDR47, WDR48, WDR49, WDR5, WDR53, WDR54,
WDR55, WDR59, WDR5B, WDR6, WDR60, WDR61, WDR62, WDR63, WDR64, WDR66,
WDR7, WDR70, WDR72, WDR73, WDR74, WDR75, WDR76, WDR77, WDR78, WDR81,
WDR82, WDR83, WDR83OS, WDR86, WDR87, WDR88, WDR89, WDR90, WDR91, WDR92,
WDR93, WDR97, WDSUB1, WDTC1, WDYHV1, WEE1, WEE2, WFDC1, WFDC10A,
WFDC10B, WFDC11, WFDC12, WFDC13, WFDC2, WFDC3, WFDC5, WFDC6, WFDC8,
WFDC9, WFIKKN1, WFIKKN2, WFS1, WHAMM, WHRN, WIF1, WIPF1, WIPF2, WIPF3,
WIPI1, WIPI2, WISP1, WISP2, WISP3, WIZ, WLS, WNK1, WNK2, WNK3, WNK4, WNT1,
WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT3A, WNT4, WNT5A,
WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9B, WRAP53,
WRAP73, WRB, WRN, WRNIP1, WSB1, WSB2, WSCD1, WSCD2, WT1, WTAP, WTH3D1,
WTIP, WWC1, WWC2, WWC3, WWOX, WWP1, WWP2, WWTR1, XAB2, XAF1, XAGEIA,
XAGE1B, XAGE2, XAGE3, XAGE5, XBP1, XCL1, XCL2, XCR1, XDH, XG, XIAP, XIRP1,
XIRP2, XK, XKR3, XKR4, XKR5, XKR6, XKR7, XKR8, XKR9, XKRX, XPA, XPC,
XPNPEP1, XPNPEP2, XPNPEP3, XPO1, XPO4, XPO5, XPO6, XPO7, XPOT, XPR1, XRCC1,
XRCC2, XRCC3, XRCC4, XRCC5, XRCC6, XRN1, XRN2, XRRA1, XXYLT1, XYLB,
XYLT1, XYLT2, YAEID1, YAF2, YAP1, YARS, YARS2, YBEY, YBX1, YBX2, YBX3,
YDJC, YEATS2, YEATS4, YES1, YIFIA, YIFIB, YIPF1, YIPF2, YIPF3, YIPF4, YIPF5,
YIPF6, YIPF7, YJEFN3, YKT6, YLPM1, YME1L1, YOD1, YPEL1, YPEL2, YPEL3, YPEL4,
YPEL5, YRDC, YTHDC1, YTHDC2, YTHDF1, YTHDF2, YTHDF3, YWHAB, YWHAE,
YWHAG, YWHAH, YWHAQ, YWHAZ, YY1, YY1AP1, YY2, Z82206.1, Z83844.1, Z84492.1,
Z98749.3, Z98752.3, ZACN, ZADH2, ZAN, ZAP70, ZAR1, ZAR1L, ZBBX, ZBED1, ZBED2,
ZBED3, ZBED4, ZBED5, ZBED6, ZBED6CL, ZBED8, ZBED9, ZBP1, ZBTB1, ZBTB10,
ZBTB11, ZBTB12, ZBTB14, ZBTB16, ZBTB17, ZBTB18, ZBTB2, ZBTB20, ZBTB21,
ZBTB22, ZBTB24, ZBTB25, ZBTB26, ZBTB3, ZBTB32, ZBTB33, ZBTB34, ZBTB37,
ZBTB38, ZBTB39, ZBTB4, ZBTB40, ZBTB41, ZBTB42, ZBTB43, ZBTB44, ZBTB45,
ZBTB46, ZBTB47, ZBTB48, ZBTB49, ZBTB5, ZBTB6, ZBTB7A, ZBTB7B, ZBTB7C,
ZBTB8A, ZBTB8B, ZBTB8OS, ZBTB9, ZC2HC1A, ZC2HC1B, ZC2HC1C, ZC3H10,
ZC3H11A, ZC3H11B, ZC3H12A, ZC3H12B, ZC3H12C, ZC3H12D, ZC3H13, ZC3H14,
ZC3H15, ZC3H18, ZC3H3, ZC3H4, ZC3H6, ZC3H7A, ZC3H7B, ZC3H8, ZC3HAV1,
ZC3HAV1L, ZC3HC1, ZC4H2, ZCCHC10, ZCCHC11, ZCCHC12, ZCCHC13, ZCCHC14,
ZCCHC17, ZCCHC18, ZCCHC2, ZCCHC24, ZCCHC3, ZCCHC4, ZCCHC6, ZCCHC7,
ZCCHC8, ZCCHC9, ZCRB1, ZCWPW1, ZCWPW2, ZDBF2, ZDHHC1, ZDHHC11,
ZDHHC11B, ZDHHC12, ZDHHC13, ZDHHC14, ZDHHC15, ZDHHC16, ZDHHC17,
ZDHHC18, ZDHHC19, ZDHHC2, ZDHHC20, ZDHHC21, ZDHHC22, ZDHHC23, ZDHHC24,
ZDHHC3, ZDHHC4, ZDHHC5, ZDHHC6, ZDHHC7, ZDHHC8, ZDHHC9, ZEB1, ZEB2, ZER1,
ZFAND1, ZFAND2A, ZFAND2B, ZFAND3, ZFAND4, ZFAND5, ZFAND6, ZFAT, ZFC3H1,
ZFHX2, ZFHX3, ZFHX4, ZFP1, ZFP14, ZFP2, ZFP28, ZFP3, ZFP30, ZFP36, ZFP36L1,
ZFP36L2, ZFP37, ZFP41, ZFP42, ZFP57, ZFP62, ZFP64, ZFP69, ZFP69B, ZFP82, ZFP90,
ZFP91, ZFP91-CNTF, ZFP92, ZFPL1, ZFPM1, ZFPM2, ZFR, ZFR2, ZFX, ZFY, ZFYVE1,
ZFYVE16, ZFYVE19, ZFYVE21, ZFYVE26, ZFYVE27, ZFYVE28, ZFYVE9, ZG16, ZG16B,
ZGLP1, ZGPAT, ZGRF1, ZHX1, ZHX1-C8orf76, ZHX2, ZHX3, ZIC1, ZIC2, ZIC3, ZIC4, ZIC5,
ZIK1, ZIM2, ZIM3, ZKSCAN1, ZKSCAN2, ZKSCAN3, ZKSCAN4, ZKSCAN5, ZKSCAN7,
ZKSCAN8, ZMAT1, ZMAT2, ZMAT3, ZMAT4, ZMAT5, ZMIZ1, ZMIZ2, ZMPSTE24,
ZMYM1, ZMYM2, ZMYM3, ZMYM4, ZMYM5, ZMYM6, ZMYND10, ZMYND11,
ZMYND12, ZMYND15, ZMYND19, ZMYND8, ZNF10, ZNF100, ZNF101, ZNF106, ZNF107,
ZNF112, ZNF114, ZNF117, ZNF12, ZNF121, ZNF124, ZNF131, ZNF132, ZNF133, ZNF134,
ZNF135, ZNF136, ZNF138, ZNF14, ZNF140, ZNF141, ZNF142, ZNF143, ZNF146, ZNF148,
ZNF154, ZNF155, ZNF157, ZNF16, ZNF160, ZNF165, ZNF169, ZNF17, ZNF174, ZNF175,
ZNF177, ZNF18, ZNF180, ZNF181, ZNF182, ZNF184, ZNF185, ZNF189, ZNF19, ZNF195,
ZNF197, ZNF2, ZNF20, ZNF200, ZNF202, ZNF205, ZNF207, ZNF208, ZNF211, ZNF212,
ZNF213, ZNF214, ZNF215, ZNF217, ZNF219, ZNF22, ZNF221, ZNF222, ZNF223, ZNF224,
ZNF225, ZNF226, ZNF227, ZNF229, ZNF23, ZNF230, ZNF232, ZNF233, ZNF234, ZNF235,
ZNF236, ZNF239, ZNF24, ZNF248, ZNF25, ZNF250, ZNF251, ZNF253, ZNF254, ZNF256,
ZNF257, ZNF26, ZNF260, ZNF263, ZNF264, ZNF266, ZNF267, ZNF268, ZNF273, ZNF274,
ZNF275, ZNF276, ZNF277, ZNF28, ZNF280A, ZNF280B, ZNF280C, ZNF280D, ZNF281,
ZNF282, ZNF283, ZNF284, ZNF285, ZNF286A, ZNF286B, ZNF287, ZNF292, ZNF296, ZNF3,
ZNF30, ZNF300, ZNF302, ZNF304, ZNF311, ZNF316, ZNF317, ZNF318, ZNF319, ZNF32,
ZNF320, ZNF322, ZNF324, ZNF324B, ZNF326, ZNF329, ZNF330, ZNF331, ZNF333, ZNF334,
ZNF335, ZNF337, ZNF33A, ZNF33B, ZNF34, ZNF341, ZNF343, ZNF345, ZNF346, ZNF347,
ZNF35, ZNF350, ZNF354A, ZNF354B, ZNF354C, ZNF358, ZNF362, ZNF365, ZNF366,
ZNF367, ZNF37A, ZNF382, ZNF383, ZNF384, ZNF385A, ZNF385B, ZNF385C, ZNF385D,
ZNF391, ZNF394, ZNF395, ZNF396, ZNF397, ZNF398, ZNF404, ZNF407, ZNF408, ZNF41,
ZNF410, ZNF414, ZNF415, ZNF416, ZNF417, ZNF418, ZNF419, ZNF420, ZNF423, ZNF425,
ZNF426, ZNF428, ZNF429, ZNF43, ZNF430, ZNF431, ZNF432, ZNF433, ZNF436, ZNF438,
ZNF439, ZNF44, ZNF440, ZNF441, ZNF442, ZNF443, ZNF444, ZNF445, ZNF446, ZNF449,
ZNF45, ZNF451, ZNF454, ZNF460, ZNF461, ZNF462, ZNF467, ZNF468, ZNF469, ZNF470,
ZNF471, ZNF473, ZNF474, ZNF479, ZNF48, ZNF480, ZNF483, ZNF484, ZNF485, ZNF486,
ZNF487, ZNF488, ZNF490, ZNF491, ZNF492, ZNF493, ZNF496, ZNF497, ZNF500, ZNF501,
ZNF502, ZNF503, ZNF506, ZNF507, ZNF510, ZNF511, ZNF512, ZNF512B, ZNF513, ZNF514,
ZNF516, ZNF517, ZNF518A, ZNF518B, ZNF519, ZNF521, ZNF524, ZNF525, ZNF526,
ZNF527, ZNF528, ZNF529, ZNF530, ZNF532, ZNF534, ZNF536, ZNF540, ZNF541, ZNF543,
ZNF544, ZNF546, ZNF547, ZNF548, ZNF549, ZNF550, ZNF551, ZNF552, ZNF554, ZNF555,
ZNF556, ZNF557, ZNF558, ZNF559, ZNF559-ZNF177, ZNF560, ZNF561, ZNF562, ZNF563,
ZNF564, ZNF565, ZNF566, ZNF567, ZNF568, ZNF569, ZNF57, ZNF570, ZNF571, ZNF572,
ZNF573, ZNF574, ZNF575, ZNF576, ZNF577, ZNF578, ZNF579, ZNF580, ZNF581, ZNF582,
ZNF583, ZNF584, ZNF585A, ZNF585B, ZNF586, ZNF587, ZNF587B, ZNF589, ZNF592,
ZNF593, ZNF594, ZNF595, ZNF596, ZNF597, ZNF598, ZNF599, ZNF600, ZNF605, ZNF606,
ZNF607, ZNF608, ZNF609, ZNF610, ZNF611, ZNF613, ZNF614, ZNF615, ZNF616, ZNF618,
ZNF619, ZNF620, ZNF621, ZNF622, ZNF623, ZNF624, ZNF625, ZNF625-ZNF20, ZNF626,
ZNF627, ZNF628, ZNF629, ZNF630, ZNF638, ZNF639, ZNF641, ZNF644, ZNF645, ZNF646,
ZNF648, ZNF649, ZNF652, ZNF653, ZNF654, ZNF655, ZNF658, ZNF66, ZNF660, ZNF662,
ZNF664, ZNF665, ZNF667, ZNF668, ZNF669, ZNF670, ZNF670-ZNF695, ZNF671, ZNF672,
ZNF674, ZNF675, ZNF676, ZNF677, ZNF678, ZNF679, ZNF680, ZNF681, ZNF682, ZNF683,
ZNF684, ZNF687, ZNF688, ZNF689, ZNF69, ZNF691, ZNF692, ZNF695, ZNF696, ZNF697,
ZNF699, ZNF7, ZNF70, ZNF700, ZNF701, ZNF703, ZNF704, ZNF705A, ZNF705B, ZNF705D,
ZNF705E, ZNF705G, ZNF706, ZNF707, ZNF708, ZNF709, ZNF71, ZNF710, ZNF711, ZNF713,
ZNF714, ZNF716, ZNF717, ZNF718, ZNF720, ZNF721, ZNF724, ZNF726, ZNF727, ZNF728,
ZNF729, ZNF730, ZNF732, ZNF735, ZNF736, ZNF737, ZNF738, ZNF74, ZNF740, ZNF746,
ZNF747, ZNF749, ZNF750, ZNF75A, ZNF75D, ZNF76, ZNF761, ZNF763, ZNF764, ZNF765,
ZNF766, ZNF768, ZNF77, ZNF770, ZNF771, ZNF772, ZNF773, ZNF774, ZNF775, ZNF776,
ZNF777, ZNF778, ZNF780A, ZNF780B, ZNF781, ZNF782, ZNF783, ZNF784, ZNF785,
ZNF786, ZNF787, ZNF788, ZNF789, ZNF79, ZNF790, ZNF791, ZNF792, ZNF793, ZNF799,
ZNF8, ZNF80, ZNF800, ZNF804A, ZNF804B, ZNF805, ZNF808, ZNF81, ZNF813, ZNF814,
ZNF816, ZNF816-ZNF321P, ZNF821, ZNF823, ZNF827, ZNF829, ZNF83, ZNF830, ZNF831,
ZNF835, ZNF836, ZNF837, ZNF839, ZNF84, ZNF841, ZNF843, ZNF844, ZNF845, ZNF846,
ZNF85, ZNF850, ZNF852, ZNF853, ZNF860, ZNF862, ZNF865, ZNF878, ZNF879, ZNF880,
ZNF883, ZNF888, ZNF891, ZNF90, ZNF91, ZNF92, ZNF93, ZNF98, ZNF99, ZNFX1, ZNHIT1,
ZNHIT2, ZNHIT3, ZNHIT6, ZNRD1, ZNRF1, ZNRF2, ZNRF3, ZNRF4, ZP1, ZP2, ZP3, ZP4,
ZPBP, ZPBP2, ZPLD1, ZPR1, ZRANB1, ZRANB2, ZRANB3, ZRSR1, ZRSR2, ZSCAN1,
ZSCAN10, ZSCAN12, ZSCAN16, ZSCAN18, ZSCAN2, ZSCAN20, ZSCAN21, ZSCAN22,
ZSCAN23, ZSCAN25, ZSCAN26, ZSCAN29, ZSCAN30, ZSCAN31, ZSCAN32, ZSCAN4,
ZSCAN5A, ZSCAN5B, ZSCAN5C, ZSCAN9, ZSWIM1, ZSWIM2, ZSWIM3, ZSWIM4,
ZSWIM5, ZSWIM6, ZSWIM7, ZSWIM8, ZUFSP, ZW10, ZWILCH, ZWINT, ZXDA, ZXDB,
ZXDC, ZYG11A, ZYG11B, ZYX, ZZEF1, and ZZZ3.
Protein Level Control
This description also provides methods for the control of protein levels with a cell. This is based on the use of compounds as described herein, which are known to interact with a specific target protein such that degradation of a target protein in vivo will result in the control of the amount of protein in a biological system, preferably to a particular therapeutic benefit.
Furthermore, the invention provides the use of a compound according to the definitions herein, or a pharmaceutically acceptable salt, or a hydrate or solvate thereof for the preparation of a medicament for the treatment of an autoimmune disorder, an inflammatory disorder, or a proliferative disorder, or a disorder commonly occurring in connection with transplantation.
Combination Therapies
Depending upon the particular condition, or disease, to be treated, additional therapeutic agents, which are normally administered to treat that condition, may be administered in combination with compounds and compositions of this invention. As used herein, additional therapeutic agents that are normally administered to treat a particular disease, or condition, are known as “appropriate for the disease, or condition, being treated.”
In certain embodiments, a provided combination, or composition thereof, is administered in combination with another therapeutic agent.
In some embodiments, the present invention provides a method of treating a disclosed disease or condition comprising administering to a patient in need thereof an effective amount of a compound disclosed herein or a pharmaceutically acceptable salt thereof and co-administering simultaneously or sequentially an effective amount of one or more additional therapeutic agents, such as those described herein. In some embodiments, the method includes co-administering one additional therapeutic agent. In some embodiments, the method includes co-administering two additional therapeutic agents. In some embodiments, the combination of the disclosed compound and the additional therapeutic agent or agents acts synergistically.
Examples of agents the combinations of this invention may also be combined with include, without limitation: treatments for Alzheimer's Disease such as Aricept® and Excelon®; treatments for HIV such as ritonavir; treatments for Parkinson's Disease such as L-DOPA/carbidopa, entacapone, ropinrole, pramipexole, bromocriptine, pergolide, trihexephendyl, and amantadine; agents for treating Multiple Sclerosis (MS) such as beta interferon (e.g., Avonex® and Rebif®), Copaxone®, and mitoxantrone; treatments for asthma such as albuterol and Singulair®; agents for treating schizophrenia such as zyprexa, risperdal, seroquel, and haloperidol; anti-inflammatory agents such as corticosteroids, TNF blockers, IL-1 RA, azathioprine, cyclophosphamide, and sulfasalazine; immunomodulatory and immunosuppressive agents such as cyclosporin, tacrolimus, rapamycin, mycophenolate mofetil, interferons, corticosteroids, cyclophophamide, azathioprine, and sulfasalazine; neurotrophic factors such as acetylcholinesterase inhibitors, MAO inhibitors, interferons, anti-convulsants, ion channel blockers, riluzole, and anti-Parkinsonian agents; agents for treating cardiovascular disease such as beta-blockers, ACE inhibitors, diuretics, nitrates, calcium channel blockers, and statins; agents for treating liver disease such as corticosteroids, cholestyramine, interferons, and anti-viral agents; agents for treating blood disorders such as corticosteroids, anti-leukemic agents, and growth factors; agents that prolong or improve pharmaco*kinetics such as cytochrome P450 inhibitors (i.e., inhibitors of metabolic breakdown) and CYP3A4 inhibitors (e.g., ketokenozole and ritonavir), and agents for treating immunodeficiency disorders such as gamma globulin.
In certain embodiments, combination therapies of the present invention, or a pharmaceutically acceptable composition thereof, are administered in combination with a monoclonal antibody or an siRNA therapeutic.
Those additional agents may be administered separately from a provided combination therapy, as part of a multiple dosage regimen. Alternatively, those agents may be part of a single dosage form, mixed together with a compound of this invention in a single composition. If administered as part of a multiple dosage regime, the two active agents may be submitted simultaneously, sequentially or within a period of time from one another normally within five hours from one another.
As used herein, the term “combination,” “combined,” and related terms refers to the simultaneous or sequential administration of therapeutic agents in accordance with this invention. For example, a combination of the present invention may be administered with another therapeutic agent simultaneously or sequentially in separate unit dosage forms or together in a single unit dosage form.
The amount of additional therapeutic agent present in the compositions of this invention will be no more than the amount that would normally be administered in a composition comprising that therapeutic agent as the only active agent. Preferably the amount of additional therapeutic agent in the presently disclosed compositions will range from about 50% to 100% of the amount normally present in a composition comprising that agent as the only therapeutically active agent.
One or more other therapeutic agent may be administered separately from a compound or composition of the invention, as part of a multiple dosage regimen. Alternatively, one or more other therapeutic agents may be part of a single dosage form, mixed together with a compound of this invention in a single composition. If administered as a multiple dosage regime, one or more other therapeutic agent and a compound or composition of the invention may be administered simultaneously, sequentially or within a period of time from one another, for example within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 18, 20, 21, 22, 23, or 24 hours from one another. In some embodiments, one or more other therapeutic agent and a compound or composition of the invention are administered as a multiple dosage regimen within greater than 24 hours apart.
In one embodiment, the present invention provides a composition comprising a provided compound or a pharmaceutically acceptable salt thereof and one or more additional therapeutic agents. The therapeutic agent may be administered together with a provided compound or a pharmaceutically acceptable salt thereof, or may be administered prior to or following administration of a provided compound or a pharmaceutically acceptable salt thereof. Suitable therapeutic agents are described in further detail below. In certain embodiments, a provided compound or a pharmaceutically acceptable salt thereof may be administered up to 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5, hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, or 18 hours before the therapeutic agent. In other embodiments, a provided compound or a pharmaceutically acceptable salt thereof may be administered up to 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5, hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, or 18 hours following the therapeutic agent.
In another embodiment, the present invention provides a method of treating an inflammatory disease, disorder or condition by administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and one or more additional therapeutic agents. Such additional therapeutic agents may be small molecules or recombinant biologic agents and include, for example, acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin, ibuprofen, naproxen, etodolac (Lodine®) and celecoxib, colchicine (Colcrys®), corticosteroids such as prednisone, prednisolone, methylprednisolone, hydrocortisone, and the like, probenecid, allopurinol, febuxostat (Uloric®), sulfasalazine (Azulfidine®), antimalarials such as hydroxychloroquine (Plaquenil®) and chloroquine (Aralen®), methotrexate (Rheumatrex®), gold salts such as gold thioglucose (Solganal®), gold thiomalate (Myochrysine®) and auranofin (Ridaura®), D-penicillamine (Depen® or Cuprimine®), azathioprine (Imuran®), cyclophosphamide (Cytoxan®), chlorambucil (Leukeran®), cyclosporine (Sandimmune®), leflunomide (Arava®) and “anti-TNF” agents such as etanercept (Enbrel®), infliximab (Remicade®), golimumab (Simponi®), certolizumab pegol (Cimzia®) and adalimumab (Humira®), “anti-IL-1” agents such as anakinra (Kineret®) and rilonacept (Arcalyst®), canakinumab (Ilaris®), anti-Jak inhibitors such as tofacitinib, antibodies such as rituximab (Rituxan®), “anti-T-cell” agents such as abatacept (Orencia®), “anti-IL-6” agents such as tocilizumab (Actemra®), diclofenac, cortisone, hyaluronic acid (Synvisc® or Hyalgan®), monoclonal antibodies such as tanezumab, anticoagulants such as heparin (Calcinparine® or Liquaemin®) and warfarin (Coumadin®), antidiarrheals such as diphenoxylate (Lomotil®) and loperamide (Imodium®), bile acid binding agents such as cholestyramine, alosetron (Lotronex®), lubiprostone (Amitiza®), laxatives such as Milk of Magnesia, polyethylene glycol (MiraLax®), Dulcolax®, Correctol® and Senokot®, anticholinergics or antispasmodics such as dicyclomine (Bentyl®), Singulair®, beta-2 agonists such as albuterol (Ventolin® HFA, Proventil® HFA), levalbuterol (Xopenex®), metaproterenol (Alupent®), pirbuterol acetate (Maxair®), terbutaline sulfate (Brethaire®), salmeterol xinafoate (Serevent®) and formoterol (Foradil®), anticholinergic agents such as ipratropium bromide (Atrovent®) and tiotropium (Spiriva®), inhaled corticosteroids such as beclomethasone dipropionate (Beclovent®, Qvar®, and Vanceril®), triamcinolone acetonide (Azmacort®), mometasone (Asthmanex®), budesonide (Pulmocort®), and flunisolide (Aerobid®), Afviar®, Symbicort®, Dulera®, cromolyn sodium (Intal®), methylxanthines such as theophylline (Theo-Dur®, Theolair®, Slo-Bid®, Uniphyl®, Theo-24®) and aminophylline, IgE antibodies such as omalizumab (Xolair®), nucleoside reverse transcriptase inhibitors such as zidovudine (Retrovir®), abacavir (Ziagen®), abacavir/lamivudine (Epzicom®), abacavir/lamivudine/zidovudine (Trizivir®), didanosine (Videx®), emtricitabine (Emtriva®), lamivudine (Epivir®), lamivudine/zidovudine (Combivir®), stavudine (Zerit®), and zalcitabine (Hivid®), non-nucleoside reverse transcriptase inhibitors such as delavirdine (Rescriptor®), efavirenz (Sustiva®), nevairapine (Viramune®) and etravirine (Intelence®), nucleotide reverse transcriptase inhibitors such as tenofovir (Viread®), protease inhibitors such as amprenavir (Agenerase®), atazanavir (Reyataz®), darunavir (Prezista®), fosamprenavir (Lexiva®), indinavir (Crixivan®), lopinavir and ritonavir (Kaletra®), nelfinavir (Viracept®), ritonavir (Norvir®), saquinavir (Fortovase® or Invirase®), and tipranavir (Aptivus®), entry inhibitors such as enfuvirtide (Fuzeon®) and maraviroc (Selzentry®), integrase inhibitors such as raltegravir (Isentress®), doxorubicin (Hydrodaunorubicin®), vincristine (Oncovin®), bortezomib (Velcade®), and dexamethasone (Decadron®) in combination with lenalidomide (Revlimid®), or any combination(s) thereof.
In another embodiment, the present invention provides a method of treating gout comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and one or more additional therapeutic agents selected from non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin, ibuprofen, naproxen, etodolac (Lodine®) and celecoxib, colchicine (Colcrys®), corticosteroids such as prednisone, prednisolone, methylprednisolone, hydrocortisone, and the like, probenecid, allopurinol and febuxostat (Uloric®).
In another embodiment, the present invention provides a method of treating rheumatoid arthritis comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and one or more additional therapeutic agents selected from non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin, ibuprofen, naproxen, etodolac (Lodine®) and celecoxib, corticosteroids such as prednisone, prednisolone, methylprednisolone, hydrocortisone, and the like, sulfasalazine (Azulfidine®), antimalarials such as hydroxychloroquine (Plaquenil®) and chloroquine (Aralen®), methotrexate (Rheumatrex®), gold salts such as gold thioglucose (Solganal®), gold thiomalate (Myochrysine®) and auranofin (Ridaura®), D-penicillamine (Depen® or Cuprimine®), azathioprine (Imuran®), cyclophosphamide (Cytoxan®), chlorambucil (Leukeran®), cyclosporine (Sandimmune®), leflunomide (Arava®) and “anti-TNF” agents such as etanercept (Enbrel®), infliximab (Remicade®), golimumab (Simponi®), certolizumab pegol (Cimzia®) and adalimumab (Humira®), “anti-IL-1” agents such as anakinra (Kineret®) and rilonacept (Arcalyst®), antibodies such as rituximab (Rituxan®), “anti-T-cell” agents such as abatacept (Orencia®) and “anti-IL-6” agents such as tocilizumab (Actemra®).
In some embodiments, the present invention provides a method of treating osteoarthritis comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and one or more additional therapeutic agents selected from acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin, ibuprofen, naproxen, etodolac (Lodine®) and celecoxib, diclofenac, cortisone, hyaluronic acid (Synvisc® or Hyalgan®) and monoclonal antibodies such as tanezumab.
In some embodiments, the present invention provides a method of treating lupus comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and one or more additional therapeutic agents selected from acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin, ibuprofen, naproxen, etodolac (Lodine®) and celecoxib, corticosteroids such as prednisone, prednisolone, methylprednisolone, hydrocortisone, and the like, antimalarials such as hydroxychloroquine (Plaquenil®) and chloroquine (Aralen®), cyclophosphamide (Cytoxan®), methotrexate (Rheumatrex®), azathioprine (Imuran®) and anticoagulants such as heparin (Calcinparine® or Liquaemin®) and warfarin (Coumadin®).
In some embodiments, the present invention provides a method of treating inflammatory bowel disease comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and one or more additional therapeutic agents selected from mesalamine (Asacol®) sulfasalazine (Azulfidine®), antidiarrheals such as diphenoxylate (Lomotil®) and loperamide (Imodium®), bile acid binding agents such as cholestyramine, alosetron (Lotronex®), lubiprostone (Amitiza®), laxatives such as Milk of Magnesia, polyethylene glycol (MiraLax®), Dulcolax®, Correctol® and Senokot® and anticholinergics or antispasmodics such as dicyclomine (Bentyl®), anti-TNF therapies, steroids, and antibiotics such as Flagyl or ciprofloxacin.
In some embodiments, the present invention provides a method of treating asthma comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and one or more additional therapeutic agents selected from Singulair®, beta-2 agonists such as albuterol (Ventolin® HFA, Proventil® HFA), levalbuterol (Xopenex®), metaproterenol (Alupent®), pirbuterol acetate (Maxair®), terbutaline sulfate (Brethaire®), salmeterol xinafoate (Serevent®) and formoterol (Foradil®), anticholinergic agents such as ipratropium bromide (Atrovent®) and tiotropium (Spiriva®), inhaled corticosteroids such as prednisone, prednisolone, beclomethasone dipropionate (Beclovent®, Qvar®, and Vanceril®), triamcinolone acetonide (Azmacort®), mometasone (Asthmanex®), budesonide (Pulmocort®), flunisolide (Aerobid®), Afviar®, Symbicort®, and Dulera®, cromolyn sodium (Intal®), methylxanthines such as theophylline (Theo-Dur®, Theolair®, Slo-Bid®, Uniphyl®, Theo-24®) and aminophylline, and IgE antibodies such as omalizumab (Xolair®).
In some embodiments, the present invention provides a method of treating COPD comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and one or more additional therapeutic agents selected from beta-2 agonists such as albuterol (Ventolin® HFA, Proventil® HFA), levalbuterol (Xopenex®), metaproterenol (Alupent®), pirbuterol acetate (Maxair®), terbutaline sulfate (Brethaire®), salmeterol xinafoate (Serevent®) and formoterol (Foradil®), anticholinergic agents such as ipratropium bromide (Atrovent®) and tiotropium (Spiriva®), methylxanthines such as theophylline (Theo-Dur®, Theolair®, Slo-Bid®, Uniphyl®, Theo-24®) and aminophylline, inhaled corticosteroids such as prednisone, prednisolone, beclomethasone dipropionate (Beclovent®, Qvar®, and Vanceril®), triamcinolone acetonide (Azmacort®), mometasone (Asthmanex®), budesonide (Pulmocort®), flunisolide (Aerobid®), Afviar®, Symbicort®, and Dulera®,
In some embodiments, the present invention provides a method of treating HIV comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and one or more additional therapeutic agents selected from nucleoside reverse transcriptase inhibitors such as zidovudine (Retrovir®), abacavir (Ziagen®), abacavir/lamivudine (Epzicom®), abacavir/lamivudine/zidovudine (Trizivir®), didanosine (Videx®), emtricitabine (Emtriva®), lamivudine (Epivir®), lamivudine/zidovudine (Combivir®), stavudine (Zerit®), and zalcitabine (Hivid®), non-nucleoside reverse transcriptase inhibitors such as delavirdine (Rescriptor®), efavirenz (Sustiva®), nevairapine (Viramune®) and etravirine (Intelence®), nucleotide reverse transcriptase inhibitors such as tenofovir (Viread®), protease inhibitors such as amprenavir (Agenerase®), atazanavir (Reyataz®), darunavir (Prezista®), fosamprenavir (Lexiva®), indinavir (Crixivan®), lopinavir and ritonavir (Kaletra®), nelfinavir (Viracept®), ritonavir (Norvir®), saquinavir (Fortovase® or Invirase®), and tipranavir (Aptivus®), entry inhibitors such as enfuvirtide (Fuzeon®) and maraviroc (Selzentry®), integrase inhibitors such as raltegravir (Isentress®), and combinations thereof.
In another embodiment, the present invention provides a method of treating a hematological malignancy comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and one or more additional therapeutic agents selected from rituximab (Rituxan®), cyclophosphamide (Cytoxan®), doxorubicin (Hydrodaunorubicin®), vincristine (Oncovin®), prednisone, a hedgehog signaling inhibitor, a BTK inhibitor, a JAK/pan-JAK inhibitor, a TYK2 inhibitor, a PI3K inhibitor, a SYK inhibitor, and combinations thereof.
In another embodiment, the present invention provides a method of treating a solid tumor comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and one or more additional therapeutic agents selected from rituximab (Rituxan®), cyclophosphamide (Cytoxan®), doxorubicin (Hydrodaunorubicin®), vincristine (Oncovin®), prednisone, a hedgehog signaling inhibitor, a BTK inhibitor, a JAK/pan-JAK inhibitor, a TYK2 inhibitor, a PI3K inhibitor, a SYK inhibitor, and combinations thereof.
In another embodiment, the present invention provides a method of treating a hematological malignancy comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and a Hedgehog (Hh) signaling pathway inhibitor. In some embodiments, the hematological malignancy is DLBCL (Ramirez et al “Defining causative factors contributing in the activation of hedgehog signaling in diffuse large B-cell lymphoma” Leuk. Res. (2012), published online July 17, and incorporated herein by reference in its entirety).
In another embodiment, the present invention provides a method of treating diffuse large B-cell lymphoma (DLBCL) comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and one or more additional therapeutic agents selected from rituximab (Rituxan®), cyclophosphamide (Cytoxan®), doxorubicin (Hydrodaunorubicin®), vincristine (Oncovin®), prednisone, a hedgehog signaling inhibitor, and combinations thereof.
In another embodiment, the present invention provides a method of treating multiple myeloma comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and one or more additional therapeutic agents selected from bortezomib (Velcade®), and dexamethasone (Decadron®), a hedgehog signaling inhibitor, a BTK inhibitor, a JAK/pan-JAK inhibitor, a TYK2 inhibitor, a PI3K inhibitor, a SYK inhibitor in combination with lenalidomide (Revlimid®).
In another embodiment, the present invention provides a method of treating Waldenström's macroglobulinemia comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and one or more additional therapeutic agents selected from chlorambucil (Leukeran®), cyclophosphamide (Cytoxan®, Neosar®), fludarabine (Fludara®), cladribine (Leustatin®), rituximab (Rituxan®), a hedgehog signaling inhibitor, a BTK inhibitor, a JAK/pan-JAK inhibitor, a TYK2 inhibitor, a PI3K inhibitor, and a SYK inhibitor.
In some embodiments, one or more other therapeutic agent is an antagonist of the hedgehog pathway. Approved hedgehog pathway inhibitors which may be used in the present invention include sonidegib (Odomzo®, Sun Pharmaceuticals); and vismodegib (Erivedge®, Genentech), both for treatment of basal cell carcinoma.
In some embodiments, one or more other therapeutic agent is a Poly ADP ribose polymerase (PARP) inhibitor. In some embodiments, a PARP inhibitor is selected from olaparib (Lynparza®, AstraZeneca); rucaparib (Rubraca®, Clovis Oncology); niraparib (Zejula®, Tesaro); talazoparib (MDV3800/BMN 673/LT00673, Medivation/Pfizer/Biomarin); veliparib (ABT-888, AbbVie); and BGB-290 (BeiGene, Inc.).
In some embodiments, one or more other therapeutic agent is a histone deacetylase (HDAC) inhibitor. In some embodiments, an HDAC inhibitor is selected from vorinostat (Zolinza®, Merck); romidepsin (Istodax®, Celgene); panobinostat (Farydak®, Novartis); belinostat (Beleodaq®, Spectrum Pharmaceuticals); entinostat (SNDX-275, Syndax Pharmaceuticals) (NCT00866333); and chidamide (Epidaza®, HBI-8000, Chipscreen Biosciences, China).
In some embodiments, one or more other therapeutic agent is a CDK inhibitor, such as a CDK4/CDK6 inhibitor. In some embodiments, a CDK 4/6 inhibitor is selected from palbociclib (Ibrance®, Pfizer); ribociclib (Kisqali®, Novartis); abemaciclib (Ly2835219, Eli Lilly); and trilaciclib (G1T28, G1 Therapeutics).
In some embodiments, one or more other therapeutic agent is a folic acid inhibitor. Approved folic acid inhibitors useful in the present invention include pemetrexed (Alimta®, Eli Lilly).
In some embodiments, one or more other therapeutic agent is a CC chemokine receptor 4 (CCR4) inhibitor. CCR4 inhibitors being studied that may be useful in the present invention include mogamulizumab (Poteligeo®, Kyowa Hakko Kirin, Japan).
In some embodiments, one or more other therapeutic agent is an isocitrate dehydrogenase (IDH) inhibitor. IDH inhibitors being studied which may be used in the present invention include AG120 (Celgene; NCT02677922); AG221 (Celgene, NCT02677922; NCT02577406); BAY1436032 (Bayer, NCT02746081); IDH305 (Novartis, NCT02987010).
In some embodiments, one or more other therapeutic agent is an arginase inhibitor. Arginase inhibitors being studied which may be used in the present invention include AEB1102 (pegylated recombinant arginase, Aeglea Biotherapeutics), which is being studied in Phase 1 clinical trials for acute myeloid leukemia and myelodysplastic syndrome (NCT02732184) and solid tumors (NCT02561234); and CB-1158 (Calithera Biosciences).
In some embodiments, one or more other therapeutic agent is a glutaminase inhibitor. Glutaminase inhibitors being studied which may be used in the present invention include CB-839 (Calithera Biosciences).
In some embodiments, one or more other therapeutic agent is an antibody that binds to tumor antigens, that is, proteins expressed on the cell surface of tumor cells. Approved antibodies that bind to tumor antigens which may be used in the present invention include rituximab (Rituxan®, Genentech/BiogenIdec); ofatumumab (anti-CD20, Arzerra®, GlaxoSmithKline); obinutuzumab (anti-CD20, Gazyva®, Genentech), ibritumomab (anti-CD20 and Yttrium-90, Zevalin®, Spectrum Pharmaceuticals); daratumumab (anti-CD38, Darzalex®, Janssen Biotech), dinutuximab (anti-glycolipid GD2, Unituxin®, United Therapeutics); trastuzumab (anti-HER2, Herceptin®, Genentech); ado-trastuzumab emtansine (anti-HER2, fused to emtansine, Kadcyla®, Genentech); and pertuzumab (anti-HER2, Perjeta®, Genentech); and brentuximab vedotin (anti-CD30-drug conjugate, Adcetris®, Seattle Genetics).
In some embodiments, one or more other therapeutic agent is a topoisomerase inhibitor. Approved topoisomerase inhibitors useful in the present invention include irinotecan (Onivyde®, Merrimack Pharmaceuticals); topotecan (Hycamtin®, GlaxoSmithKline). Topoisomerase inhibitors being studied which may be used in the present invention include pixantrone (Pixuvri®, CTI Biopharma).
In some embodiments, one or more other therapeutic agent is an inhibitor of anti-apoptotic proteins, such as BCL-2. Approved anti-apoptotics which may be used in the present invention include venetoclax (Venclexta®, AbbVie/Genentech); and blinatumomab (Blincyto®, Amgen). Other therapeutic agents targeting apoptotic proteins which have undergone clinical testing and may be used in the present invention include navitoclax (ABT-263, Abbott), a BCL-2 inhibitor (NCT02079740).
In some embodiments, one or more other therapeutic agent is an androgen receptor inhibitor. Approved androgen receptor inhibitors useful in the present invention include enzalutamide (Xtandi®, Astellas/Medivation); approved inhibitors of androgen synthesis include abiraterone (Zytiga®, Centocor/Ortho); approved antagonist of gonadotropin-releasing hormone (GnRH) receptor (degaralix, Firmagon®, Ferring Pharmaceuticals).
In some embodiments, one or more other therapeutic agent is a selective estrogen receptor modulator (SERM), which interferes with the synthesis or activity of estrogens. Approved SERMs useful in the present invention include raloxifene (Evista®, Eli Lilly).
In some embodiments, one or more other therapeutic agent is an inhibitor of bone resorption. An approved therapeutic which inhibits bone resorption is Denosumab (Xgeva®, Amgen), an antibody that binds to RANKL, prevents binding to its receptor RANK, found on the surface of osteoclasts, their precursors, and osteoclast-like giant cells, which mediates bone pathology in solid tumors with osseous metastases. Other approved therapeutics that inhibit bone resorption include bisphosphonates, such as zoledronic acid (Zometa®, Novartis).
In some embodiments, one or more other therapeutic agent is an inhibitor of interaction between the two primary p53 suppressor proteins, MDMX and MDM2. Inhibitors of p53 suppression proteins being studied which may be used in the present invention include ALRN-6924 (Aileron), a stapled peptide that equipotently binds to and disrupts the interaction of MDMX and MDM2 with p53. ALRN-6924 is currently being evaluated in clinical trials for the treatment of AML, advanced myelodysplastic syndrome (MDS) and peripheral T-cell lymphoma (PTCL) (NCT02909972; NCT02264613).
In some embodiments, one or more other therapeutic agent is an inhibitor of transforming growth factor-beta (TGF-beta or TGFβ). Inhibitors of TGF-beta proteins being studied which may be used in the present invention include NIS793 (Novartis), an anti-TGF-beta antibody being tested in the clinic for treatment of various cancers, including breast, lung, hepatocellular, colorectal, pancreatic, prostate and renal cancer (NCT 02947165). In some embodiments, the inhibitor of TGF-beta proteins is fresolimumab (GC1008; Sanofi-Genzyme), which is being studied for melanoma (NCT00923169); renal cell carcinoma (NCT00356460); and non-small cell lung cancer (NCT02581787). Additionally, in some embodiments, the additional therapeutic agent is a TGF-beta trap, such as described in Connolly et al. (2012) Int'l J. Biological Sciences 8:964-978. One therapeutic compound currently in clinical trials for treatment of solid tumors is M7824 (Merck KgaA—formerly MSB0011459X), which is a bispecific, anti-PD-L1/TGFβ trap compound (NCT02699515); and (NCT02517398). M7824 is comprised of a fully human IgG1 antibody against PD-L1 fused to the extracellular domain of human TGF-beta receptor II, which functions as a TGFβ “trap.”
In some embodiments, one or more other therapeutic agent is selected from glembatumumab vedotin-monomethyl auristatin E (MMAE) (Celldex), an anti-glycoprotein NMB (gpNMB) antibody (CR011) linked to the cytotoxic MMAE. gpNMB is a protein overexpressed by multiple tumor types associated with cancer cells' ability to metastasize.
In some embodiments, one or more other therapeutic agent is an antiproliferative compound. Such antiproliferative compounds include, but are not limited to aromatase inhibitors; antiestrogens; topoisomerase I inhibitors; topoisomerase II inhibitors; microtubule active compounds; alkylating compounds; histone deacetylase inhibitors; compounds which induce cell differentiation processes; cyclooxygenase inhibitors; MMP inhibitors; mTOR inhibitors; antineoplastic antimetabolites; platin compounds; compounds targeting/decreasing a protein or lipid kinase activity and further anti-angiogenic compounds; compounds which target, decrease or inhibit the activity of a protein or lipid phosphatase; gonadorelin agonists; anti-androgens; methionine aminopeptidase inhibitors; matrix metalloproteinase inhibitors; bisphosphonates; biological response modifiers; antiproliferative antibodies; heparanase inhibitors; inhibitors of Ras oncogenic isoforms; telomerase inhibitors; proteasome inhibitors; compounds used in the treatment of hematologic malignancies; compounds which target, decrease or inhibit the activity of Flt-3; Hsp90 inhibitors such as 17-AAG (17-allylaminogeldanamycin, NSC330507), 17-DMAG (17-dimethylaminoethylamino-17-demethoxy-geldanamycin, NSC707545), IPI-504, CNF1010, CNF2024, CNF1010 from Conforma Therapeutics; temozolomide (Temodal c)); kinesin spindle protein inhibitors, such as SB715992 or SB743921 from GlaxoSmithKline, or pentamidine/chlorpromazine from CombinatoRx; MEK inhibitors such as ARRY142886 from Array BioPharma, AZd6244 from AstraZeneca, PD181461 from Pfizer and leucovorin.
In some embodiments, the present invention provides a method of treating Alzheimer's disease comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and one or more additional therapeutic agents selected from donepezil (Aricept®), rivastigmine (Excelon®), galantamine (Razadyne®), tacrine (Cognex®), and memantine (Namenda®).
In some embodiments, one or more other therapeutic agent is a taxane compound, which causes disruption of microtubules, which are essential for cell division. In some embodiments, a taxane compound is selected from pacl*taxel (Taxol®, Bristol-Myers Squibb), docetaxel (Taxotere®, Sanofi-Aventis; Docefrez®, Sun Pharmaceutical), albumin-bound pacl*taxel (Abraxane®; Abraxis/Celgene), cabazitaxel (Jevtana®, Sanofi-Aventis), and SID530 (SK Chemicals, Co.) (NCT00931008).
In some embodiments, one or more other therapeutic agent is a nucleoside inhibitor, or a therapeutic agent that interferes with normal DNA synthesis, protein synthesis, cell replication, or will otherwise inhibit rapidly proliferating cells.
In some embodiments, a nucleoside inhibitor is selected from trabectedin (guanidine alkylating agent, Yondelis®, Janssen Oncology), mechlorethamine (alkylating agent, Valchlor®, Aktelion Pharmaceuticals); vincristine (Oncovin®, Eli Lilly; Vincasar®, Teva Pharmaceuticals; Marqibo®, Talon Therapeutics); temozolomide (prodrug to alkylating agent 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC) Temodar®, Merck); cytarabine injection (ara-C, antimetabolic cytidine analog, Pfizer); lomustine (alkylating agent, CeeNU®, Bristol-Myers Squibb; Gleostine®, NextSource Biotechnology); azacitidine (pyrimidine nucleoside analog of cytidine, Vidaza®, Celgene); omacetaxine mepesuccinate (cephalotaxine ester) (protein synthesis inhibitor, Synribo®; Teva Pharmaceuticals); asparaginase Erwinia chrysanthemi (enzyme for depletion of asparagine, Elspar®, Lundbeck; Erwinaze®, EUSA Pharma); eribulin mesylate (microtubule inhibitor, tubulin-based antimitotic, Halaven®, Eisai); cabazitaxel (microtubule inhibitor, tubulin-based antimitotic, Jevtana®, Sanofi-Aventis); capacetrine (thymidylate synthase inhibitor, Xeloda®, Genentech); bendamustine (bifunctional mechlorethamine derivative, believed to form interstrand DNA cross-links, Treanda®, Cephalon/Teva); ixabepilone (semi-synthetic analog of epothilone B, microtubule inhibitor, tubulin-based antimitotic, Ixempra®, Bristol-Myers Squibb); nelarabine (prodrug of deoxyguanosine analog, nucleoside metabolic inhibitor, Arranon®, Novartis); clorafabine (prodrug of ribonucleotide reductase inhibitor, competitive inhibitor of deoxycytidine, Clolar®, Sanofi-Aventis); and trifluridine and tipiracil (thymidine-based nucleoside analog and thymidine phosphorylase inhibitor, Lonsurf®, Taiho Oncology).
In some embodiments, one or more other therapeutic agent is a kinase inhibitor or VEGF-R antagonist. Approved VEGF inhibitors and kinase inhibitors useful in the present invention include: bevacizumab (Avastin®, Genentech/Roche) an anti-VEGF monoclonal antibody; ramucirumab (Cyramza®, Eli Lilly), an anti-VEGFR-2 antibody and ziv-aflibercept, also known as VEGF Trap (Zaltrap®; Regeneron/Sanofi). VEGFR inhibitors, such as regorafenib (Stivarga®, Bayer); vandetanib (Caprelsa®, AstraZeneca); axitinib (Inlyta®, Pfizer); and lenvatinib (Lenvima®, Eisai); Raf inhibitors, such as sorafenib (Nexavar®, Bayer AG and Onyx); dabrafenib (Tafinlar®, Novartis); and vemurafenib (Zelboraf®, Genentech/Roche); MEK inhibitors, such as cobimetanib (Cotellic®, Exelexis/Genentech/Roche); trametinib (Mekinist®, Novartis); Bcr-Abl tyrosine kinase inhibitors, such as imatinib (Gleevec®, Novartis); nilotinib (Tasigna®, Novartis); dasatinib (Sprycel®, BristolMyersSquibb); bosutinib (Bosulif®, Pfizer); and ponatinib (Inclusig®, Ariad Pharmaceuticals); Her2 and EGFR inhibitors, such as gefitinib (Iressa®, AstraZeneca); erlotinib (Tarceeva®, Genentech/Roche/Astellas); lapatinib (Tykerb®, Novartis); afatinib (Gilotrif®, Boehringer Ingelheim); osimertinib (targeting activated EGFR, Tagrisso®, AstraZeneca); and brigatinib (Alunbrig®, Ariad Pharmaceuticals); c-Met and VEGFR2 inhibitors, such as cabozanitib (Cometriq®, Exelexis); and multikinase inhibitors, such as sunitinib (Sutent®, Pfizer); pazopanib (Votrient®, Novartis); ALK inhibitors, such as crizotinib (Xalkori®, Pfizer); ceritinib (Zykadia®, Novartis); and alectinib (Alecenza®, Genentech/Roche); Bruton's tyrosine kinase inhibitors, such as ibrutinib (Imbruvica®, Pharmacyclics/Janssen); and Flt3 receptor inhibitors, such as midostaurin (Rydapt®, Novartis).
Other kinase inhibitors and VEGF-R antagonists that are in development and may be used in the present invention include tivozanib (Aveo Pharmaecuticals); vatalanib (Bayer/Novartis); lucitanib (Clovis Oncology); dovitinib (TKI258, Novartis); Chiauanib (Chipscreen Biosciences); CEP-11981 (Cephalon); linifanib (Abbott Laboratories); neratinib (HKI-272, Puma Biotechnology); radotinib (Supect®, IY5511, Il-Yang Pharmaceuticals, S. Korea); ruxolitinib (Jakafi®, Incyte Corporation); PTC299 (PTC Therapeutics); CP-547,632 (Pfizer); foretinib (Exelexis, GlaxoSmithKline); quizartinib (Daiichi Sankyo) and motesanib (Amgen/Takeda).
In another embodiment, the present invention provides a method of treating organ transplant rejection or graft vs. host disease comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and one or more additional therapeutic agents selected from a steroid, cyclosporin, FK506, rapamycin, a hedgehog signaling inhibitor, a BTK inhibitor, a JAK/pan-JAK inhibitor, a TYK2 inhibitor, a PI3K inhibitor, and a SYK inhibitor.
In another embodiment, the present invention provides a method of treating or lessening the severity of a disease comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and a BTK inhibitor, wherein the disease is selected from inflammatory bowel disease, arthritis, systemic lupus erythematosus (SLE), vasculitis, idiopathic thrombocytopenic purpura (ITP), rheumatoid arthritis, psoriatic arthritis, osteoarthritis, Still's disease, juvenile arthritis, diabetes, myasthenia gravis, Hashimoto's thyroiditis, Ord's thyroiditis, Graves' disease, autoimmune thyroiditis, Sjogren's syndrome, multiple sclerosis, systemic sclerosis, Lyme neuroborreliosis, Guillain-Barre syndrome, acute disseminated encephalomyelitis, Addison's disease, opsoclonus-myoclonus syndrome, ankylosing spondylosis, antiphospholipid antibody syndrome, aplastic anemia, autoimmune hepatitis, autoimmune gastritis, pernicious anemia, celiac disease, Goodpasture's syndrome, idiopathic thrombocytopenic purpura, optic neuritis, scleroderma, primary biliary cirrhosis, Reiter's syndrome, Takayasu's arteritis, temporal arteritis, warm autoimmune hemolytic anemia, Wegener's granulomatosis, psoriasis, alopecia universalis, Behcet's disease, chronic fatigue, dysautonomia, membranous glomerulonephropathy, endometriosis, interstitial cystitis, pemphigus vulgaris, bullous pemphigoid, neuromyotonia, scleroderma, vulvodynia, a hyperproliferative disease, rejection of transplanted organs or tissues, Acquired Immunodeficiency Syndrome (AIDS, also known as HIV), type 1 diabetes, graft versus host disease, transplantation, transfusion, anaphylaxis, allergies (e.g., allergies to plant pollens, latex, drugs, foods, insect poisons, animal hair, animal dander, dust mites, or co*ckroach calyx), type I hypersensitivity, allergic conjunctivitis, allergic rhinitis, and atopic dermatitis, asthma, appendicitis, atopic dermatitis, asthma, allergy, blepharitis, bronchiolitis, bronchitis, bursitis, cervicitis, cholangitis, cholecystitis, chronic graft rejection, colitis, conjunctivitis, Crohn's disease, cystitis, dacryoadenitis, dermatitis, dermatomyositis, encephalitis, endocarditis, endometritis, enteritis, enterocolitis, epicondylitis, epididymitis, fasciitis, fibrositis, gastritis, gastroenteritis, Henoch-Schonlein purpura, hepatitis, hidradenitis suppurativa, immunoglobulin A nephropathy, interstitial lung disease, laryngitis, mastitis, meningitis, myelitis myocarditis, myositis, nephritis, oophoritis, orchitis, osteitis, otitis, pancreatitis, parotitis, pericarditis, peritonitis, pharyngitis, pleuritis, phlebitis, pneumonitis, pneumonia, polymyositis, proctitis, prostatitis, pyelonephritis, rhinitis, salpingitis, sinusitis, stomatitis, synovitis, tendonitis, tonsillitis, ulcerative colitis, uveitis, vaginitis, vasculitis, or vulvitis, B-cell proliferative disorder, e.g., diffuse large B cell lymphoma, follicular lymphoma, chronic lymphocytic lymphoma, chronic lymphocytic leukemia, acute lymphocytic leukemia, B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia, splenic marginal zone lymphoma, multiple myeloma (also known as plasma cell myeloma), non-Hodgkin's lymphoma, Hodgkin's lymphoma, plasmacytoma, extranodal marginal zone B cell lymphoma, nodal marginal zone B cell lymphoma, mantle cell lymphoma, mediastinal (thymic) large B cell lymphoma, intravascular large B cell lymphoma, primary effusion lymphoma, Burkitt lymphoma/leukemia, or lymphomatoid granulomatosis, breast cancer, prostate cancer, or cancer of the mast cells (e.g., mastocytoma, mast cell leukemia, mast cell sarcoma, systemic mastocytosis), bone cancer, colorectal cancer, pancreatic cancer, diseases of the bone and joints including, without limitation, rheumatoid arthritis, seronegative spondyloarthropathies (including ankylosing spondylitis, psoriatic arthritis and Reiter's disease), Behcet's disease, Sjogren's syndrome, systemic sclerosis, osteoporosis, bone cancer, bone metastasis, a thromboembolic disorder, (e.g., myocardial infarct, angina pectoris, reocclusion after angioplasty, restenosis after angioplasty, reocclusion after aortocoronary bypass, restenosis after aortocoronary bypass, stroke, transitory ischemia, a peripheral arterial occlusive disorder, pulmonary embolism, deep venous thrombosis), inflammatory pelvic disease, urethritis, skin sunburn, sinusitis, pneumonitis, encephalitis, meningitis, myocarditis, nephritis, osteomyelitis, myositis, hepatitis, gastritis, enteritis, dermatitis, gingivitis, appendicitis, pancreatitis, cholocystitus, agammaglobulinemia, psoriasis, allergy, Crohn's disease, irritable bowel syndrome, ulcerative colitis, Sjogren's disease, tissue graft rejection, hyperacute rejection of transplanted organs, asthma, allergic rhinitis, chronic obstructive pulmonary disease (COPD), autoimmune polyglandular disease (also known as autoimmune polyglandular syndrome), autoimmune alopecia, pernicious anemia, glomerulonephritis, dermatomyositis, multiple sclerosis, scleroderma, vasculitis, autoimmune hemolytic and thrombocytopenic states, Goodpasture's syndrome, atherosclerosis, Addison's disease, Parkinson's disease, Alzheimer's disease, diabetes, septic shock, systemic lupus erythematosus (SLE), rheumatoid arthritis, psoriatic arthritis, juvenile arthritis, osteoarthritis, chronic idiopathic thrombocytopenic purpura, Waldenstrom macroglobulinemia, myasthenia gravis, Hashimoto's thyroiditis, atopic dermatitis, degenerative joint disease, vitiligo, autoimmune hypopituitarism, Guillain-Barre syndrome, Behcet's disease, scleraderma, mycosis fungoides, acute inflammatory responses (such as acute respiratory distress syndrome and ischemia/reperfusion injury), and Graves' disease.
In another embodiment, the present invention provides a method of treating or lessening the severity of a disease comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and a PI3K inhibitor, wherein the disease is selected from a cancer, a neurodegenative disorder, an angiogenic disorder, a viral disease, an autoimmune disease, an inflammatory disorder, a hormone-related disease, conditions associated with organ transplantation, immunodeficiency disorders, a destructive bone disorder, a proliferative disorder, an infectious disease, a condition associated with cell death, thrombin-induced platelet aggregation, chronic myelogenous leukemia (CIVIL), chronic lymphocytic leukemia (CLL), liver disease, pathologic immune conditions involving T cell activation, a cardiovascular disorder, and a CNS disorder.
In another embodiment, the present invention provides a method of treating or lessening the severity of a disease comprising administering to a patient in need thereof a provided compound or a pharmaceutically acceptable salt thereof and a PI3K inhibitor, wherein the disease is selected from benign or malignant tumor, carcinoma or solid tumor of the brain, kidney (e.g., renal cell carcinoma (RCC)), liver, adrenal gland, bladder, breast, stomach, gastric tumors, ovaries, colon, rectum, prostate, pancreas, lung, vagin*, endometrium, cervix, testis, genitourinary tract, esophagus, larynx, skin, bone or thyroid, sarcoma, glioblastomas, neuroblastomas, multiple myeloma or gastrointestinal cancer, especially colon carcinoma or colorectal adenoma or a tumor of the neck and head, an epidermal hyperproliferation, psoriasis, prostate hyperplasia, a neoplasia, a neoplasia of epithelial character, adenoma, adenocarcinoma, keratoacanthoma, epidermoid carcinoma, large cell carcinoma, non-small-cell lung carcinoma, lymphomas, (including, for example, non-Hodgkin's Lymphoma (NHL) and Hodgkin's lymphoma (also termed Hodgkin's or Hodgkin's disease)), a mammary carcinoma, follicular carcinoma, undifferentiated carcinoma, papillary carcinoma, seminoma, melanoma, or a leukemia, diseases include Cowden syndrome, Lhermitte-Dudos disease and Bannayan-Zonana syndrome, or diseases in which the PI3K/PKB pathway is aberrantly activated, asthma of whatever type or genesis including both intrinsic (non-allergic) asthma and extrinsic (allergic) asthma, mild asthma, moderate asthma, severe asthma, bronchitic asthma, exercise-induced asthma, occupational asthma and asthma induced following bacterial infection, acute lung injury (ALI), adult/acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary, airways or lung disease (COPD, COAD or COLD), including chronic bronchitis or dyspnea associated therewith, emphysema, as well as exacerbation of airways hyperreactivity consequent to other drug therapy, in particular other inhaled drug therapy, bronchitis of whatever type or genesis including, but not limited to, acute, arachidic, catarrhal, croupus, chronic or phthinoid bronchitis, pneumoconiosis (an inflammatory, commonly occupational, disease of the lungs, frequently accompanied by airways obstruction, whether chronic or acute, and occasioned by repeated inhalation of dusts) of whatever type or genesis, including, for example, aluminosis, anthracosis, asbestosis, chalicosis, ptilosis, siderosis, silicosis, tabacosis and byssinosis, Loffler's syndrome, eosinophilic, pneumonia, parasitic (in particular metazoan) infestation (including tropical eosinophilia), bronchopulmonary aspergillosis, polyarteritis nodosa (including Churg-Strauss syndrome), eosinophilic granuloma and eosinophil-related disorders affecting the airways occasioned by drug-reaction, psoriasis, contact dermatitis, atopic dermatitis, alopecia areata, erythema multiforma, dermatitis herpetiformis, scleroderma, vitiligo, hypersensitivity angiitis, urticaria, bullous pemphigoid, lupus erythematosus, pemphisus, epidermolysis bullosa acquisita, conjunctivitis, keratoconjunctivitis sicca, and vernal conjunctivitis, diseases affecting the nose including allergic rhinitis, and inflammatory disease in which autoimmune reactions are implicated or having an autoimmune component or etiology, including autoimmune hematological disorders (e.g. hemolytic anemia, aplastic anemia, pure red cell anemia and idiopathic thrombocytopenia), systemic lupus erythematosus, rheumatoid arthritis, polychondritis, sclerodoma, Wegener granulamatosis, dermatomyositis, chronic active hepatitis, myasthenia gravis, Steven-Johnson syndrome, idiopathic sprue, autoimmune inflammatory bowel disease (e.g. ulcerative colitis and Crohn's disease), endocrine opthalmopathy, Grave's disease, sarcoidosis, alveolitis, chronic hypersensitivity pneumonitis, multiple sclerosis, primary biliary cirrhosis, uveitis (anterior and posterior), keratoconjunctivitis sicca and vernal keratoconjunctivitis, interstitial lung fibrosis, psoriatic arthritis and glomerulonephritis (with and without nephrotic syndrome, e.g. including idiopathic nephrotic syndrome or minal change nephropathy, restenosis, cardiomegaly, atherosclerosis, myocardial infarction, ischemic stroke and congestive heart failure, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and cerebral ischemia, and neurodegenerative disease caused by traumatic injury, glutamate neurotoxicity and hypoxia.
In some embodiments, one or more other therapeutic agent is a phosphatidylinositol 3 kinase (PI3K) inhibitor. In some embodiments, a PI3K inhibitor is selected from idelalisib (Zydelig®, Gilead), alpelisib (BYL719, Novartis), taselisib (GDC-0032, Genentech/Roche); pictilisib (GDC-0941, Genentech/Roche); copanlisib (BAY806946, Bayer); duvelisib (formerly IPI-145, Infinity Pharmaceuticals); PQR309 (Piqur Therapeutics, Switzerland); and TGR1202 (formerly RP5230, TG Therapeutics).
The compounds and compositions, according to the method of the present invention, may be administered using any amount and any route of administration effective for treating or lessening the severity of a cancer, an autoimmune disorder, a proliferative disorder, an inflammatory disorder, a neurodegenerative or neurological disorder, schizophrenia, a bone-related disorder, liver disease, or a cardiac disorder. The exact amount required will vary from subject to subject, depending on the species, age, and general condition of the subject, the severity of the infection, the particular agent, its mode of administration, and the like. Compounds of the invention are preferably formulated in dosage unit form for ease of administration and uniformity of dosage. The expression “dosage unit form” as used herein refers to a physically discrete unit of agent appropriate for the patient to be treated. It will be understood, however, that the total daily usage of the compounds and compositions of the present invention will be decided by the attending physician within the scope of sound medical judgment. The specific effective dose level for any particular patient or organism will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed, and like factors well known in the medical arts. The term “patient”, as used herein, means an animal, preferably a mammal, and most preferably a human.
Pharmaceutically acceptable compositions of this invention can be administered to humans and other animals orally, rectally, parenterally, intracisternally, intravagin*lly, intraperitoneally, topically (as by powders, ointments, or drops), bucally, as an oral or nasal spray, or the like, depending on the severity of the infection being treated. In certain embodiments, the compounds of the invention may be administered orally or parenterally at dosage levels of about 0.01 mg/kg to about 50 mg/kg and preferably from about 1 mg/kg to about 25 mg/kg, of subject body weight per day, one or more times a day, to obtain the desired therapeutic effect.
Liquid dosage forms for oral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents.
Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution, suspension or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, U.S.P. and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables.
Injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use.
In order to prolong the effect of a compound of the present invention, it is often desirable to slow the absorption of the compound from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the compound then depends upon its rate of dissolution that, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered compound form is accomplished by dissolving or suspending the compound in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the compound in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of compound to polymer and the nature of the particular polymer employed, the rate of compound release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the compound in liposomes or microemulsions that are compatible with body tissues.
Compositions for rectal or vagin*l administration are preferably suppositories which can be prepared by mixing the compounds of this invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vagin*l cavity and release the active compound.
Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarding agents such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents.
Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polethylene glycols and the like.
The active compounds can also be in micro-encapsulated form with one or more excipients as noted above. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings and other coatings well known in the pharmaceutical formulating art. In such solid dosage forms the active compound may be admixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, e.g., tableting lubricants and other tableting aids such a magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes.
Dosage forms for topical or transdermal administration of a compound of this invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. The active component is admixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives or buffers as may be required. Ophthalmic formulation, ear drops, and eye drops are also contemplated as being within the scope of this invention. Additionally, the present invention contemplates the use of transdermal patches, which have the added advantage of providing controlled delivery of a compound to the body. Such dosage forms can be made by dissolving or dispensing the compound in the proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate can be controlled by either providing a rate controlling membrane or by dispersing the compound in a polymer matrix or gel.
According to one embodiment, the invention relates to a method of inhibiting protein kinase activity or degrading a protein kinase in a biological sample comprising the step of contacting said biological sample with a compound of this invention, or a composition comprising said compound.
According to another embodiment, the invention relates to a method of inhibiting or degrading IRAK-1, IRAK-2, and/or IRAK-4, or a mutant thereof, activity in a biological sample comprising the step of contacting said biological sample with a compound of this invention, or a composition comprising said compound.
The term “biological sample”, as used herein, includes, without limitation, cell cultures or extracts thereof; biopsied material obtained from a mammal or extracts thereof; and blood, saliva, urine, feces, sem*n, tears, or other body fluids or extracts thereof.
Inhibition and/or degradation of a protein kinase, or a protein kinase selected from IRAK-1, IRAK-2, and/or IRAK-4, or a mutant thereof, activity in a biological sample is useful for a variety of purposes that are known to one of skill in the art. Examples of such purposes include, but are not limited to, blood transfusion, organ-transplantation, biological specimen storage, and biological assays.
Another embodiment of the present invention relates to a method of degrading a protein kinase and/or inhibiting protein kinase activity in a patient comprising the step of administering to said patient a compound of the present invention, or a composition comprising said compound.
According to another embodiment, the invention relates to a method of degrading and/or inhibiting one or more of IRAK-1, IRAK-2, and/or IRAK-4, or a mutant thereof, activity in a patient comprising the step of administering to said patient a compound of the present invention, or a composition comprising said compound. In other embodiments, the present invention provides a method for treating a disorder mediated by one or more of IRAK-1, IRAK-2, and/or IRAK-4, or a mutant thereof, in a patient in need thereof, comprising the step of administering to said patient a compound according to the present invention or pharmaceutically acceptable composition thereof. Such disorders are described in detail herein.
Depending upon the particular condition, or disease, to be treated, additional therapeutic agents that are normally administered to treat that condition, may also be present in the compositions of this invention. As used herein, additional therapeutic agents that are normally administered to treat a particular disease, or condition, are known as “appropriate for the disease, or condition, being treated.”
A compound of the current invention may also be used to advantage in combination with other antiproliferative compounds. Such antiproliferative compounds include, but are not limited to aromatase inhibitors; antiestrogens; topoisomerase I inhibitors; topoisomerase II inhibitors; microtubule active compounds; alkylating compounds; histone deacetylase inhibitors; compounds which induce cell differentiation processes; cyclooxygenase inhibitors; MMP inhibitors; mTOR inhibitors; antineoplastic antimetabolites; platin compounds; compounds targeting/decreasing a protein or lipid kinase activity and further anti-angiogenic compounds; compounds which target, decrease or inhibit the activity of a protein or lipid phosphatase; gonadorelin agonists; anti-androgens; methionine aminopeptidase inhibitors; matrix metalloproteinase inhibitors; bisphosphonates; biological response modifiers; antiproliferative antibodies; heparanase inhibitors; inhibitors of Ras oncogenic isoforms; telomerase inhibitors; proteasome inhibitors; compounds used in the treatment of hematologic malignancies; compounds which target, decrease or inhibit the activity of Flt-3; Hsp90 inhibitors such as 17-AAG (17-allylaminogeldanamycin, NSC330507), 17-DMAG (17-dimethylaminoethylamino-17-demethoxy-geldanamycin, NSC707545), IPI-504, CNF1010, CNF2024, CNF1010 from Conforma Therapeutics; temozolomide (Temodal c)); kinesin spindle protein inhibitors, such as SB715992 or SB743921 from GlaxoSmithKline, or pentamidine/chlorpromazine from CombinatoRx; MEK inhibitors such as ARRY142886 from Array BioPharma, AZD6244 from AstraZeneca, PD181461 from Pfizer and leucovorin.
The term “aromatase inhibitor” as used herein relates to a compound which inhibits estrogen production, for instance, the conversion of the substrates androstenedione and testosterone to estrone and estradiol, respectively. The term includes, but is not limited to steroids, especially atamestane, exemestane and formestane and, in particular, non-steroids, especially aminoglutethimide, roglethimide, pyridoglutethimide, trilostane, testolactone, ketokonazole, vorozole, fadrozole, anastrozole and letrozole. Exemestane is marketed under the trade name Aromasin™. Formestane is marketed under the trade name Lentaron™. Fadrozole is marketed under the trade name Afema™. Anastrozole is marketed under the trade name Arimidex™ Letrozole is marketed under the trade names Femara™ or Femar™. Aminoglutethimide is marketed under the trade name Orimeten™. A combination of the invention comprising a chemotherapeutic agent which is an aromatase inhibitor is particularly useful for the treatment of hormone receptor positive tumors, such as breast tumors.
In some embodiments, one or more other therapeutic agent is an mTOR inhibitor, which inhibits cell proliferation, angiogenesis and glucose uptake. In some embodiments, an mTOR inhibitor is everolimus (Afinitor®, Novartis); temsirolimus (Torisel®, Pfizer); and sirolimus (Rapamune®, Pfizer).
In some embodiments, one or more other therapeutic agent is an aromatase inhibitor. In some embodiments, an aromatase inhibitor is selected from exemestane (Aromasin®, Pfizer); anastazole (Arimidex®, AstraZeneca) and letrozole (Femora®, Novartis).
The term “antiestrogen” as used herein relates to a compound which antagonizes the effect of estrogens at the estrogen receptor level. The term includes, but is not limited to tamoxifen, fulvestrant, raloxifene and raloxifene hydrochloride. Tamoxifen is marketed under the trade name Nolvadex™. Raloxifene hydrochloride is marketed under the trade name Evista™. Fulvestrant can be administered under the trade name Faslodex™. A combination of the invention comprising a chemotherapeutic agent which is an antiestrogen is particularly useful for the treatment of estrogen receptor positive tumors, such as breast tumors.
The term “anti-androgen” as used herein relates to any substance which is capable of inhibiting the biological effects of androgenic hormones and includes, but is not limited to, bicalutamide (Casodex™). The term “gonadorelin agonist” as used herein includes, but is not limited to abarelix, goserelin and goserelin acetate. Goserelin can be administered under the trade name Zoladex™.
The term “topoisomerase I inhibitor” as used herein includes, but is not limited to topotecan, gimatecan, irinotecan, camptothecian and its analogues, 9-nitrocamptothecin and the macromolecular camptothecin conjugate PNU-166148. Irinotecan can be administered, e.g. in the form as it is marketed, e.g. under the trademark Camptosar™. Topotecan is marketed under the trade name Hycamptin™.
The term “topoisomerase II inhibitor” as used herein includes, but is not limited to the anthracyclines such as doxorubicin (including liposomal formulation, such as Caelyx™) daunorubicin, epirubicin, idarubicin and nemorubicin, the anthraquinones mitoxantrone and losoxantrone, and the podophillotoxines etoposide and teniposide. Etoposide is marketed under the trade name Etopophos™. Teniposide is marketed under the trade name VM 26-Bristol Doxorubicin is marketed under the trade name Acriblastin™ or Adriamycin™. Epirubicin is marketed under the trade name Farmorubicin™. Idarubicin is marketed. under the trade name Zavedos™. Mitoxantrone is marketed under the trade name Novantron.
The term “microtubule active agent” relates to microtubule stabilizing, microtubule destabilizing compounds and microtublin polymerization inhibitors including, but not limited to taxanes, such as pacl*taxel and docetaxel; vinca alkaloids, such as vinblastine or vinblastine sulfate, vincristine or vincristine sulfate, and vinorelbine; discodermolides; cochicine and epothilones and derivatives thereof. Pacl*taxel is marketed under the trade name Taxol™. Docetaxel is marketed under the trade name Taxotere™. Vinblastine sulfate is marketed under the trade name Vinblastin R.P™. Vincristine sulfate is marketed under the trade name Farmistin™.
The term “alkylating agent” as used herein includes, but is not limited to, cyclophosphamide, ifosfamide, melphalan or nitrosourea (BCNU or Gliadel). Cyclophosphamide is marketed under the trade name Cyclostin™. Ifosfamide is marketed under the trade name Holoxan™.
The term “histone deacetylase inhibitors” or “HDAC inhibitors” relates to compounds which inhibit the histone deacetylase and which possess antiproliferative activity. This includes, but is not limited to, suberoylanilide hydroxamic acid (SAHA).
The term “antineoplastic antimetabolite” includes, but is not limited to, 5-fluorouracil or 5-FU, capecitabine, gemcitabine, DNA demethylating compounds, such as 5-azacytidine and decitabine, methotrexate and edatrexate, and folic acid antagonists such as pemetrexed. Capecitabine is marketed under the trade name Xeloda™. Gemcitabine is marketed under the trade name Gemzar™.
The term “platin compound” as used herein includes, but is not limited to, carboplatin, cis-platin, cisplatinum and oxaliplatin. Carboplatin can be administered, e.g., in the form as it is marketed, e.g. under the trademark Carboplat™. Oxaliplatin can be administered, e.g., in the form as it is marketed, e.g. under the trademark Eloxatin™.
The term “Bcl-2 inhibitor” as used herein includes, but is not limited to compounds having inhibitory activity against B-cell lymphoma 2 protein (Bcl-2), including but not limited to ABT-199, ABT-731, ABT-737, apogossypol, Ascenta's pan-Bcl-2 inhibitors, curcumin (and analogs thereof), dual Bcl-2/Bcl-xL inhibitors (Infinity Pharmaceuticals/Novartis Pharmaceuticals), Genasense (G3139), HA14-1 (and analogs thereof; see WO 2008/118802, US 2010/0197686), navitoclax (and analogs thereof, see U.S. Pat. No. 7,390,799), NH-1 (Shenayng Pharmaceutical University), obatoclax (and analogs thereof, see WO 2004/106328, US 2005/0014802), 5-001 (Gloria Pharmaceuticals), TW series compounds (Univ. of Michigan), and venetoclax. In some embodiments the Bcl-2 inhibitor is a small molecule therapeutic. In some embodiments the Bcl-2 inhibitor is a peptidomimetic.
The term “compounds targeting/decreasing a protein or lipid kinase activity; or a protein or lipid phosphatase activity; or further anti-angiogenic compounds” as used herein includes, but is not limited to, protein tyrosine kinase and/or serine and/or threonine kinase inhibitors or lipid kinase inhibitors, such as a) compounds targeting, decreasing or inhibiting the activity of the platelet-derived growth factor-receptors (PDGFR), such as compounds which target, decrease or inhibit the activity of PDGFR, especially compounds which inhibit the PDGF receptor, such as an N-phenyl-2-pyrimidine-amine derivative, such as imatinib, SU101, SU6668 and GFB-111; b) compounds targeting, decreasing or inhibiting the activity of the fibroblast growth factor-receptors (FGFR); c) compounds targeting, decreasing or inhibiting the activity of the insulin-like growth factor receptor I (IGF-IR), such as compounds which target, decrease or inhibit the activity of IGF-IR, especially compounds which inhibit the kinase activity of IGF-I receptor, or antibodies that target the extracellular domain of IGF-I receptor or its growth factors; d) compounds targeting, decreasing or inhibiting the activity of the Trk receptor tyrosine kinase family, or ephrin B4 inhibitors; e) compounds targeting, decreasing or inhibiting the activity of the AxI receptor tyrosine kinase family; f) compounds targeting, decreasing or inhibiting the activity of the Ret receptor tyrosine kinase; g) compounds targeting, decreasing or inhibiting the activity of the Kit/SCFR receptor tyrosine kinase, such as imatinib; h) compounds targeting, decreasing or inhibiting the activity of the C-kit receptor tyrosine kinases, which are part of the PDGFR family, such as compounds which target, decrease or inhibit the activity of the c-Kit receptor tyrosine kinase family, especially compounds which inhibit the c-Kit receptor, such as imatinib; i) compounds targeting, decreasing or inhibiting the activity of members of the c-Abl family, their gene-fusion products (e.g. BCR-Abl kinase) and mutants, such as compounds which target decrease or inhibit the activity of c-Abl family members and their gene fusion products, such as an N-phenyl-2-pyrimidine-amine derivative, such as imatinib or nilotinib (AMN107); PD180970; AG957; NSC 680410; PD173955 from ParkeDavis; or dasatinib (BMS-354825); j) compounds targeting, decreasing or inhibiting the activity of members of the protein kinase C (PKC) and Raf family of serine/threonine kinases, members of the MEK, SRC, JAK/pan-JAK, FAK, PDK1, PKB/Akt, Ras/MAPK, PI3K, SYK, TYK2, BTK and TEC family, and/or members of the cyclin-dependent kinase family (CDK) including staurosporine derivatives, such as midostaurin; examples of further compounds include UCN-01, safingol, BAY 43-9006, Bryostatin 1, Perifosine; llmofosine; RO 318220 and RO 320432; GO 6976; lsis 3521; LY333531/LY379196; isochinoline compounds; FTIs; PD184352 or QAN697 (a P13K inhibitor) or AT7519 (CDK inhibitor); k) compounds targeting, decreasing or inhibiting the activity of protein-tyrosine kinase inhibitors, such as compounds which target, decrease or inhibit the activity of protein-tyrosine kinase inhibitors include imatinib mesylate (Gleevec™) or tyrphostin such as Tyrphostin A23/RG-50810; AG 99; Tyrphostin AG 213; Tyrphostin AG 1748; Tyrphostin AG 490; Tyrphostin B44; Tyrphostin B44 (+) enantiomer; Tyrphostin AG 555; AG 494; Tyrphostin AG 556, AG957 and adaphostin (4-{[(2,5-dihydroxyphenyl)methyl]amino}-benzoic acid adamantyl ester; NSC 680410, adaphostin); 1) compounds targeting, decreasing or inhibiting the activity of the epidermal growth factor family of receptor tyrosine kinases (EGFR1 ErbB2, ErbB3, ErbB4 as hom*o- or heterodimers) and their mutants, such as compounds which target, decrease or inhibit the activity of the epidermal growth factor receptor family are especially compounds, proteins or antibodies which inhibit members of the EGF receptor tyrosine kinase family, such as EGF receptor, ErbB2, ErbB3 and ErbB4 or bind to EGF or EGF related ligands, CP 358774, ZD 1839, ZM 105180; trastuzumab (Herceptin™), cetuximab (Erbitux™), Iressa, Tarceva, OSI-774, Cl-1033, EKB-569, GW-2016, E1.1, E2.4, E2.5, E6.2, E6.4, E2.11, E6.3 or E7.6.3, and 7H-pyrrolo-[2,3-d]pyrimidine derivatives; m) compounds targeting, decreasing or inhibiting the activity of the c-Met receptor, such as compounds which target, decrease or inhibit the activity of c-Met, especially compounds which inhibit the kinase activity of c-Met receptor, or antibodies that target the extracellular domain of c-Met or bind to HGF, n) compounds targeting, decreasing or inhibiting the kinase activity of one or more JAK family members (JAK1/JAK2/JAK3/TYK2 and/or pan-JAK), including but not limited to PRT-062070, SB-1578, baricitinib, pacritinib, momelotinib, VX-509, AZD-1480, TG-101348, tofacitinib, and ruxolitinib; o) compounds targeting, decreasing or inhibiting the kinase activity of PI3 kinase (PI3K) including but not limited to ATU-027, SF-1126, DS-7423, PBI-05204, GSK-2126458, ZSTK-474, buparlisib, pictrelisib, PF-4691502, BYL-719, dactolisib, XL-147, XL-765, and idelalisib; and; and q) compounds targeting, decreasing or inhibiting the signaling effects of hedgehog protein (Hh) or smoothened receptor (SMO) pathways, including but not limited to cyclopamine, vismodegib, itraconazole, erismodegib, and IPI-926 (saridegib).
Compounds which target, decrease or inhibit the activity of a protein or lipid phosphatase are e.g. inhibitors of phosphatase 1, phosphatase 2A, or CDC25, such as okadaic acid or a derivative thereof.
In some embodiments, one or more other therapeutic agent is a growth factor antagonist, such as an antagonist of platelet-derived growth factor (PDGF), or epidermal growth factor (EGF) or its receptor (EGFR). Approved PDGF antagonists which may be used in the present invention include olaratumab (Lartruvo®; Eli Lilly). Approved EGFR antagonists which may be used in the present invention include cetuximab (Erbitux®, Eli Lilly); necitumumab (Portrazza®, Eli Lilly), panitumumab (Vectibix®, Amgen); and osimertinib (targeting activated EGFR, Tagrisso®, AstraZeneca).
The term “PI3K inhibitor” as used herein includes, but is not limited to compounds having inhibitory activity against one or more enzymes in the phosphatidylinositol-3-kinase family, including, but not limited to PI3Kα, PI3Kγ, PI3Kδ, PI3Kβ, PI3K-C2α, PI3K-C2β, PI3K-C2γ, Vps34, p110-α, p110-β, p110-γ, p110-δ, p85-α, p85-β, p55-γ, p150, p101, and p87. Examples of PI3K inhibitors useful in this invention include but are not limited to ATU-027, SF-1126, DS-7423, PBI-05204, GSK-2126458, ZSTK-474, buparlisib, pictrelisib, PF-4691502, BYL-719, dactolisib, XL-147, XL-765, and idelalisib.
The term “BTK inhibitor” as used herein includes, but is not limited to compounds having inhibitory activity against Bruton's Tyrosine Kinase (BTK), including, but not limited to AVL-292 and ibrutinib.
The term “SYK inhibitor” as used herein includes, but is not limited to compounds having inhibitory activity against spleen tyrosine kinase (SYK), including but not limited to PRT-062070, R-343, R-333, Excellair, PRT-062607, and fostamatinib
Further examples of BTK inhibitory compounds, and conditions treatable by such compounds in combination with compounds of this invention can be found in WO 2008/039218, US 2008/0108636 and WO 2011/090760, US 2010/0249092, the entirety of each of which is herein incorporated by reference.
Further examples of SYK inhibitory compounds, and conditions treatable by such compounds in combination with compounds of this invention can be found in WO 2003/063794, US 2004/0029902, WO 2005/007623, US 2005/0075306, and WO 2006/078846, US 2006/0211657, the entirety of each of which is herein incorporated by reference.
Further examples of PI3K inhibitory compounds, and conditions treatable by such compounds in combination with compounds of this invention can be found in WO 2004/019973, US 2004/0106569, WO 2004/089925, US 2004/0242631, U.S. Pat. No. 8,138,347, WO 2002/088112, US 2004/0116421, WO 2007/084786, US 2010/0249126, WO 2007/129161, US 2008/0076768, WO 2006/122806, US 2008/0194579, WO 2005/113554, US 2008/0275067, and WO 2007/044729, US 2010/0087440, the entirety of each of which is herein incorporated by reference.
Further examples of JAK inhibitory compounds, and conditions treatable by such compounds in combination with compounds of this invention can be found in WO 2009/114512, US 2009/0233903, WO 2008/109943, US 2010/0197671, WO 2007/053452, US 2007/0191405, WO 2001/0142246, US 2001/0053782, and WO 2007/070514, US 2007/0135461, the entirety of each of which is herein incorporated by reference.
Further anti-angiogenic compounds include compounds having another mechanism for their activity, e.g. unrelated to protein or lipid kinase inhibition e.g. thalidomide (Thalomid™) and TNP-470.
Examples of proteasome inhibitors useful for use in combination with compounds of the invention include, but are not limited to bortezomib, disulfiram, epigallocatechin-3-gallate (EGCG), salinosporamide A, carfilzomib, ONX-0912, CEP-18770, and MLN9708.
Compounds which target, decrease or inhibit the activity of a protein or lipid phosphatase are e.g. inhibitors of phosphatase 1, phosphatase 2A, or CDC25, such as okadaic acid or a derivative thereof.
Compounds which induce cell differentiation processes include, but are not limited to, retinoic acid, α- γ- or δ-tocopherol or α- γ- or δ-tocotrienol.
The term cyclooxygenase inhibitor as used herein includes, but is not limited to, Cox-2 inhibitors, 5-alkyl substituted 2-arylaminophenylacetic acid and derivatives, such as celecoxib (Celebrex™), rofecoxib (Vioxx™), etoricoxib, valdecoxib or a 5-alkyl-2-arylaminophenylacetic acid, such as 5-methyl-2-(2′-chloro-6′-fluoroanilino)phenyl acetic acid, lumiracoxib.
The term “bisphosphonates” as used herein includes, but is not limited to, etridonic, clodronic, tiludronic, pamidronic, alendronic, ibandronic, risedronic and zoledronic acid. Etridonic acid is marketed under the trade name Didronel™. Clodronic acid is marketed under the trade name Bonefos™. Tiludronic acid is marketed under the trade name Skelid™. Pamidronic acid is marketed under the trade name Aredia™. Alendronic acid is marketed under the trade name Fosamax™. Ibandronic acid is marketed under the trade name Bondranat™. Risedronic acid is marketed under the trade name Actonel™. Zoledronic acid is marketed under the trade name Zometa™. The term “mTOR inhibitors” relates to compounds which inhibit the mammalian target of rapamycin (mTOR) and which possess antiproliferative activity such as sirolimus (Rapamune®), everolimus (Certican™), CCI-779 and ABT578.
The term “heparanase inhibitor” as used herein refers to compounds which target, decrease or inhibit heparin sulfate degradation. The term includes, but is not limited to, PI-88. The term “biological response modifier” as used herein refers to a lymphokine or interferons.
The term “inhibitor of Ras oncogenic isoforms”, such as H-Ras, K-Ras, or N-Ras, as used herein refers to compounds which target, decrease or inhibit the oncogenic activity of Ras; for example, a “farnesyl transferase inhibitor” such as L-744832, DK8G557 or R115777 (Zarnestra™). The term “telomerase inhibitor” as used herein refers to compounds which target, decrease or inhibit the activity of telomerase. Compounds which target, decrease or inhibit the activity of telomerase are especially compounds which inhibit the telomerase receptor, such as telomestatin.
The term “methionine aminopeptidase inhibitor” as used herein refers to compounds which target, decrease or inhibit the activity of methionine aminopeptidase. Compounds which target, decrease or inhibit the activity of methionine aminopeptidase include, but are not limited to, bengamide or a derivative thereof.
The term “proteasome inhibitor” as used herein refers to compounds which target, decrease or inhibit the activity of the proteasome. Compounds which target, decrease or inhibit the activity of the proteasome include, but are not limited to, Bortezomib (Velcade™); carfilzomib (Kyprolis®, Amgen); and ixazomib (Ninlaro®, Takeda), and MLN 341.
The term “matrix metalloproteinase inhibitor” or (“MMP” inhibitor) as used herein includes, but is not limited to, collagen peptidomimetic and nonpeptidomimetic inhibitors, tetracycline derivatives, e.g. hydroxamate peptidomimetic inhibitor batimastat and its orally bioavailable analogue marimastat (BB-2516), prinomastat (AG3340), metastat (NSC 683551) BMS-279251, BAY 12-9566, TAA211, MMI270B or AAJ996.
The term “compounds used in the treatment of hematologic malignancies” as used herein includes, but is not limited to, FMS-like tyrosine kinase inhibitors, which are compounds targeting, decreasing or inhibiting the activity of FMS-like tyrosine kinase receptors (Flt-3R); interferon, 1-β-D-arabinofuransylcytosine (ara-c) and bisulfan; and ALK inhibitors, which are compounds which target, decrease or inhibit anaplastic lymphoma kinase.
Compounds which target, decrease or inhibit the activity of FMS-like tyrosine kinase receptors (Flt-3R) are especially compounds, proteins or antibodies which inhibit members of the Flt-3R receptor kinase family, such as PKC412, midostaurin, a staurosporine derivative, SU11248 and MLN518.
The term “HSP90 inhibitors” as used herein includes, but is not limited to, compounds targeting, decreasing or inhibiting the intrinsic ATPase activity of HSP90; degrading, targeting, decreasing or inhibiting the HSP90 client proteins via the ubiquitin proteosome pathway. Compounds targeting, decreasing or inhibiting the intrinsic ATPase activity of HSP90 are especially compounds, proteins or antibodies which inhibit the ATPase activity of HSP90, such as 17-allylamino, 17-demethoxygeldanamycin (17AAG), a geldanamycin derivative; other geldanamycin related compounds; radicicol and HDAC inhibitors.
The term “antiproliferative antibodies” as used herein includes, but is not limited to, trastuzumab (Herceptin™), Trastuzumab-DM1, erbitux, bevacizumab (Avastin™), rituximab (Rituxan®), PRO64553 (anti-CD40) and 2C4 Antibody. By antibodies is meant intact monoclonal antibodies, polyclonal antibodies, multispecific antibodies formed from at least 2 intact antibodies, and antibodies fragments so long as they exhibit the desired biological activity.
For the treatment of acute myeloid leukemia (AML), compounds of the current invention can be used in combination with standard leukemia therapies, especially in combination with therapies used for the treatment of AML. In particular, compounds of the current invention can be administered in combination with, for example, farnesyl transferase inhibitors and/or other drugs useful for the treatment of AML, such as Daunorubicin, Adriamycin, Ara-C, VP-16, Teniposide, Mitoxantrone, Idarubicin, Carboplatinum and PKC412.
Other anti-leukemic compounds include, for example, Ara-C, a pyrimidine analog, which is the 2′-alpha-hydroxy ribose (arabinoside) derivative of deoxycytidine. Also included is the purine analog of hypoxanthine, 6-mercaptopurine (6-MP) and fludarabine phosphate. Compounds which target, decrease or inhibit activity of histone deacetylase (HDAC) inhibitors such as sodium butyrate and suberoylanilide hydroxamic acid (SAHA) inhibit the activity of the enzymes known as histone deacetylases. Specific HDAC inhibitors include MS275, SAHA, FK228 (formerly FR901228), Trichostatin A and compounds disclosed in U.S. Pat. No. 6,552,065 including, but not limited to, N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)-ethyl]-amino]methyl]phenyl]-2E-2-propenamide, or a pharmaceutically acceptable salt thereof and N-hydroxy-3-[4-[(2-hydroxyethyl){2-(1H-indol-3-yl)ethyl]-amino]methyl]phenyl]-2E-2-propenamide, or a pharmaceutically acceptable salt thereof, especially the lactate salt. Somatostatin receptor antagonists as used herein refer to compounds which target, treat or inhibit the somatostatin receptor such as octreotide, and SOM230. Tumor cell damaging approaches refer to approaches such as ionizing radiation. The term “ionizing radiation” referred to above and hereinafter means ionizing radiation that occurs as either electromagnetic rays (such as X-rays and gamma rays) or particles (such as alpha and beta particles). Ionizing radiation is provided in, but not limited to, radiation therapy and is known in the art. See Hellman, Principles of Radiation Therapy, Cancer, in Principles and Practice of Oncology, Devita et al., Eds., 4th Edition, Vol. 1, pp. 248-275 (1993).
Also included are EDG binders and ribonucleotide reductase inhibitors. The term “EDG binders” as used herein refers to a class of immunosuppressants that modulates lymphocyte recirculation, such as FTY720. The term “ribonucleotide reductase inhibitors” refers to pyrimidine or purine nucleoside analogs including, but not limited to, fludarabine and/or cytosine arabinoside (ara-C), 6-thioguanine, 5-fluorouracil, cladribine, 6-mercaptopurine (especially in combination with ara-C against ALL) and/or pentostatin. Ribonucleotide reductase inhibitors are especially hydroxyurea or 2-hydroxy-1H-isoindole-1,3-dione derivatives.
Also included are in particular those compounds, proteins or monoclonal antibodies of VEGF such as 1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine or a pharmaceutically acceptable salt thereof, 1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine succinate; Angiostatin™; Endostatin™; anthranilic acid amides; ZD4190; ZD6474; SU5416; SU6668; bevacizumab; or anti-VEGF antibodies or anti-VEGF receptor antibodies, such as rhuMAb and RHUFab, VEGF aptamer such as Macugon; FLT-4 inhibitors, FLT-3 inhibitors, VEGFR-2 IgGI antibody, Angiozyme (RPI 4610) and Bevacizumab (Avastin™).
Photodynamic therapy as used herein refers to therapy which uses certain chemicals known as photosensitizing compounds to treat or prevent cancers. Examples of photodynamic therapy include treatment with compounds, such as Visudyne™ and porfimer sodium.
Angiostatic steroids as used herein refers to compounds which block or inhibit angiogenesis, such as, e.g., anecortave, triamcinolone, hydrocortisone, 11-α-epihydrocotisol, cortexolone, 17α-hydroxyprogesterone, corticosterone, desoxycorticosterone, testosterone, estrone and dexamethasone.
Implants containing corticosteroids refers to compounds, such as fluocinolone and dexamethasone.
Other chemotherapeutic compounds include, but are not limited to, plant alkaloids, hormonal compounds and antagonists; biological response modifiers, preferably lymphokines or interferons; antisense oligonucleotides or oligonucleotide derivatives; shRNA or siRNA; or miscellaneous compounds or compounds with other or unknown mechanism of action.
The compounds of the invention are also useful as co-therapeutic compounds for use in combination with other drug substances such as anti-inflammatory, bronchodilatory or antihistamine drug substances, particularly in the treatment of obstructive or inflammatory airways diseases such as those mentioned hereinbefore, for example as potentiators of therapeutic activity of such drugs or as a means of reducing required dosaging or potential side effects of such drugs. A compound of the invention may be mixed with the other drug substance in a fixed pharmaceutical composition or it may be administered separately, before, simultaneously with or after the other drug substance. Accordingly the invention includes a combination of a compound of the invention as hereinbefore described with an anti-inflammatory, bronchodilatory, antihistamine or anti-tussive drug substance, said compound of the invention and said drug substance being in the same or different pharmaceutical composition.
Suitable anti-inflammatory drugs include steroids, in particular glucocorticosteroids such as budesonide, beclamethasone dipropionate, fluticasone propionate, ciclesonide or mometasone furoate; non-steroidal glucocorticoid receptor agonists; LTB4 antagonists such LY293111, CGS025019C, CP-195543, SC-53228, BIIL 284, ONO 4057, SB 209247; LTD4 antagonists such as montelukast and zafirlukast; PDE4 inhibitors such cilomilast (Ariflo® GlaxoSmithKline), Roflumilast (Byk Gulden), V-11294A (Napp), BAY19-8004 (Bayer), SCH-351591 (Schering-Plough), Arofylline (Almirall Prodesfarma), PD189659/PD168787 (ParkeDavis), AWD-12-281 (Asta Medica), CDC-801 (Celgene), SeICID™ CC-10004 (Celgene), VM554/UM565 (Vernalis), T-440 (Tanabe), KW-4490 (Kyowa Hakko Kogyo); A2a agonists; A2b antagonists; and beta-2 adrenoceptor agonists such as albuterol (salbutamol), metaproterenol, terbutaline, salmeterol fenoterol, procaterol, and especially, formoterol and pharmaceutically acceptable salts thereof. Suitable bronchodilatory drugs include anticholinergic or antimuscarinic compounds, in particular ipratropium bromide, oxitropium bromide, tiotropium salts and CHF 4226 (Chiesi), and glycopyrrolate.
Suitable antihistamine drug substances include cetirizine hydrochloride, acetaminophen, clemastine fumarate, promethazine, loratidine, desloratidine, diphenhydramine and fexofenadine hydrochloride, activastine, astemizole, azelastine, ebastine, epinastine, mizolastine and tefenadine.
Other useful combinations of compounds of the invention with anti-inflammatory drugs are those with antagonists of chemokine receptors, e.g. CCR-1, CCR-2, CCR-3, CCR-4, CCR-5, CCR-6, CCR-7, CCR-8, CCR-9 and CCR10, CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, particularly CCR-5 antagonists such as Schering-Plough antagonists SC-351125, SCH-55700 and SCH-D, and Takeda antagonists such as N-[[4-[[[6,7-dihydro-2-(4-methylphenyl)-5H-benzo-cyclohepten-8-yl]carbonyl]amino]phenyl]-methyl]tetrahydro-N,N-dimethyl-2H-pyran-4-aminium chloride (TAK-770).
The structure of the active compounds identified by code numbers, generic or trade names may be taken from the actual edition of the standard compendium “The Merck Index” or from databases, e.g. Patents International (e.g. IMS World Publications).
A compound of the current invention may also be used in combination with known therapeutic processes, for example, the administration of hormones or radiation. In certain embodiments, a provided compound is used as a radiosensitizer, especially for the treatment of tumors which exhibit poor sensitivity to radiotherapy.
A compound of the current invention can be administered alone or in combination with one or more other therapeutic compounds, possible combination therapy taking the form of fixed combinations or the administration of a compound of the invention and one or more other therapeutic compounds being staggered or given independently of one another, or the combined administration of fixed combinations and one or more other therapeutic compounds. A compound of the current invention can besides or in addition be administered especially for tumor therapy in combination with chemotherapy, radiotherapy, immunotherapy, phototherapy, surgical intervention, or a combination of these. Long-term therapy is equally possible as is adjuvant therapy in the context of other treatment strategies, as described above. Other possible treatments are therapy to maintain the patient's status after tumor regression, or even chemopreventive therapy, for example in patients at risk.
Those additional agents may be administered separately from an inventive compound-containing composition, as part of a multiple dosage regimen. Alternatively, those agents may be part of a single dosage form, mixed together with a compound of this invention in a single composition. If administered as part of a multiple dosage regime, the two active agents may be submitted simultaneously, sequentially or within a period of time from one another normally within five hours from one another.
As used herein, the term “combination,” “combined,” and related terms refers to the simultaneous or sequential administration of therapeutic agents in accordance with this invention. For example, a compound of the present invention may be administered with another therapeutic agent simultaneously or sequentially in separate unit dosage forms or together in a single unit dosage form. Accordingly, the present invention provides a single unit dosage form comprising a compound of the current invention, an additional therapeutic agent, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
The amount of both an inventive compound and additional therapeutic agent (in those compositions which comprise an additional therapeutic agent as described above) that may be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. Preferably, compositions of this invention should be formulated so that a dosage of between 0.01-100 mg/kg body weight/day of an inventive compound can be administered.
In those compositions which comprise an additional therapeutic agent, that additional therapeutic agent and the compound of this invention may act synergistically. Therefore, the amount of additional therapeutic agent in such compositions will be less than that required in a monotherapy utilizing only that therapeutic agent. In such compositions a dosage of between 0.01-1,000 μg/kg body weight/day of the additional therapeutic agent can be administered.
The amount of one or more other therapeutic agent present in the compositions of this invention may be no more than the amount that would normally be administered in a composition comprising that therapeutic agent as the only active agent. Preferably the amount of one or more other therapeutic agent in the presently disclosed compositions will range from about 50% to 100% of the amount normally present in a composition comprising that agent as the only therapeutically active agent. In some embodiments, one or more other therapeutic agent is administered at a dosage of about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, or about 95% of the amount normally administered for that agent. As used herein, the phrase “normally administered” means the amount an FDA approved therapeutic agent is approved for dosing per the FDA label insert.
The compounds of this invention, or pharmaceutical compositions thereof, may also be incorporated into compositions for coating an implantable medical device, such as prostheses, artificial valves, vascular grafts, stents and catheters. Vascular stents, for example, have been used to overcome restenosis (re-narrowing of the vessel wall after injury). However, patients using stents or other implantable devices risk clot formation or platelet activation. These unwanted effects may be prevented or mitigated by pre-coating the device with a pharmaceutically acceptable composition comprising a kinase inhibitor. Implantable devices coated with a compound of this invention are another embodiment of the present invention.
Exemplary Immuno-Oncology Agents
In some embodiments, one or more other therapeutic agent is an immuno-oncology agent. As used herein, the term “an immuno-oncology agent” refers to an agent which is effective to enhance, stimulate, and/or up-regulate immune responses in a subject. In some embodiments, the administration of an immuno-oncology agent with a compound of the invention has a synergic effect in treating a cancer.
An immuno-oncology agent can be, for example, a small molecule drug, an antibody, or a biologic or small molecule. Examples of biologic immuno-oncology agents include, but are not limited to, cancer vaccines, antibodies, and cytokines. In some embodiments, an antibody is a monoclonal antibody. In some embodiments, a monoclonal antibody is humanized or human.
In some embodiments, an immuno-oncology agent is (i) an agonist of a stimulatory (including a co-stimulatory) receptor or (ii) an antagonist of an inhibitory (including a co-inhibitory) signal on T cells, both of which result in amplifying antigen-specific T cell responses.
Certain of the stimulatory and inhibitory molecules are members of the immunoglobulin super family (IgSF). One important family of membrane-bound ligands that bind to co-stimulatory or co-inhibitory receptors is the B7 family, which includes B7-1, B7-2, B7-H1 (PD-L1), B7-DC (PD-L2), B7-H2 (ICOS-L), B7-H3, B7-H4, B7-H5 (VISTA), and B7-H6. Another family of membrane bound ligands that bind to co-stimulatory or co-inhibitory receptors is the TNF family of molecules that bind to cognate TNF receptor family members, which includes CD40 and CD40L, OX-40, OX-40L, CD70, CD27L, CD30, CD30L, 4-1BBL, CD137 (4-1BB), TRAIL/Apo2-L, TRAILR1/DR4, TRAILR2/DR5, TRAILR3, TRAILR4, OPG, RANK, RANKL, TWEAKR/Fn14, TWEAK, BAFFR, EDAR, XEDAR, TACI, APRIL, BCMA, LTβR, LIGHT, DcR3, HVEM, VEGI/TL1A, TRAMP/DR3, EDAR, EDA1, XEDAR, EDA2, TNFR1, Lymphotoxin α/TNFβ, TNFR2, TNFα, LTβR, Lymphotoxin α1β2, FAS, FASL, RELT, DR6, TROY, NGFR.
In some embodiments, an immuno-oncology agent is a cytokine that inhibits T cell activation (e.g., IL-6, IL-10, TGF-β, VEGF, and other immunosuppressive cytokines) or a cytokine that stimulates T cell activation, for stimulating an immune response.
In some embodiments, a combination of a compound of the invention and an immuno-oncology agent can stimulate T cell responses. In some embodiments, an immuno-oncology agent is: (i) an antagonist of a protein that inhibits T cell activation (e.g., immune checkpoint inhibitors) such as CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, TIM-3, Galectin 9, CEACAM-1, BTLA, CD69, Galectin-1, TIGIT, CD113, GPR56, VISTA, 2B4, CD48, GARP, PD1H, LAIR1, TIM-1, and TIM-4; or (ii) an agonist of a protein that stimulates T cell activation such as B7-1, B7-2, CD28, 4-1BB (CD137), 4-1BBL, ICOS, ICOS-L, OX40, OX40L, GITR, GITRL, CD70, CD27, CD40, DR3 and CD28H.
In some embodiments, an immuno-oncology agent is an antagonist of inhibitory receptors on NK cells or an agonists of activating receptors on NK cells. In some embodiments, an immuno-oncology agent is an antagonists of KIR, such as lirilumab.
In some embodiments, an immuno-oncology agent is an agent that inhibits or depletes macrophages or monocytes, including but not limited to CSF-1R antagonists such as CSF-1R antagonist antibodies including RG7155 (WO 2011/070024, US 2011/0165156, WO 2011/0107553, US 2012/0329997, WO 2011/131407, US 2013/0005949, WO 2013/087699, US 2014/0336363, WO 2013/119716, WO 2013/132044, US 2014/0079706) or FPA-008 (WO 2011/140249, US 2011/0274683; WO 2013/169264; WO 2014/036357, US 2014/0079699).
In some embodiments, an immuno-oncology agent is selected from agonistic agents that ligate positive costimulatory receptors, blocking agents that attenuate signaling through inhibitory receptors, antagonists, and one or more agents that increase systemically the frequency of anti-tumor T cells, agents that overcome distinct immune suppressive pathways within the tumor microenvironment (e.g., block inhibitory receptor engagement (e.g., PD-L1/PD-1 interactions), deplete or inhibit Tregs (e.g., using an anti-CD25 monoclonal antibody (e.g., daclizumab) or by ex vivo anti-CD25 bead depletion), inhibit metabolic enzymes such as IDO, or reverse/prevent T cell energy or exhaustion) and agents that trigger innate immune activation and/or inflammation at tumor sites.
In some embodiments, an immuno-oncology agent is a CTLA-4 antagonist. In some embodiments, a CTLA-4 antagonist is an antagonistic CTLA-4 antibody. In some embodiments, an antagonistic CTLA-4 antibody is YERVOY (ipilimumab) or tremelimumab.
In some embodiments, an immuno-oncology agent is a PD-1 antagonist. In some embodiments, a PD-1 antagonist is administered by infusion. In some embodiments, an immuno-oncology agent is an antibody or an antigen-binding portion thereof that binds specifically to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, a PD-1 antagonist is an antagonistic PD-1 antibody. In some embodiments, an antagonistic PD-1 antibody is OPDIVO (nivolumab), KEYTRUDA (pembrolizumab), or MEDI-0680 (AMP-514; WO2012/145493). In some embodiments, an immuno-oncology agent may be pidilizumab (CT-011). In some embodiments, an immuno-oncology agent is a recombinant protein composed of the extracellular domain of PD-L2 (B7-DC) fused to the Fc portion of IgG1, called AMP-224.
In some embodiments, an immuno-oncology agent is a PD-L1 antagonist. In some embodiments, a PD-L1 antagonist is an antagonistic PD-L1 antibody. In some embodiments, a PD-L1 antibody is MPDL3280A (RG7446; WO 2010/077634, US 2010/0203056), durvalumab (MEDI4736), BMS-936559 (WO 2007/005874, US 2009/0055944), and MSB0010718C (WO 2013/079174, US 2014/0341917).
In some embodiments, an immuno-oncology agent is a LAG-3 antagonist. In some embodiments, a LAG-3 antagonist is an antagonistic LAG-3 antibody. In some embodiments, a LAG3 antibody is BMS-986016 (WO 2010/019570, US 2010/0150892, WO 2014/008218, US 2014/0093511), or IMP-731 or IMP-321 (WO 2008/132601, US 2010/0233183, WO 2009/044273, US 2011/0008331).
In some embodiments, an immuno-oncology agent is a CD137 (4-1BB) agonist. In some embodiments, a CD137 (4-1BB) agonist is an agonistic CD137 antibody. In some embodiments, a CD137 antibody is urelumab or PF-05082566 (WO12/32433).
In some embodiments, an immuno-oncology agent is a GITR agonist. In some embodiments, a GITR agonist is an agonistic GITR antibody. In some embodiments, a GITR antibody is BMS-986153, BMS-986156, TRX-518 (WO 2006/105021, US 2007/0098719, WO 2009/009116, US 2009/0136494), or MK-4166 (WO 2011/028683, US 2012/0189639).
In some embodiments, an immuno-oncology agent is an indoleamine (2,3)-dioxygenase (IDO) antagonist. In some embodiments, an IDO antagonist is selected from epacadostat (INCB024360, Incyte); indoximod (NLG-8189, NewLink Genetics Corporation); capmanitib (INC280, Novartis); GDC-0919 (Genentech/Roche); PF-06840003 (Pfizer); BMS:F001287 (Bristol-Myers Squibb); Phy906/KD108 (Phytoceutica); an enzyme that breaks down kynurenine (Kynase, Kyn Therapeutics); and NLG-919 (WO 2009/073620, US 2011/0053941, WO 2009/132238, US 2011/0136796, WO 2011/056652, US 2012/0277217, WO 2012/142237, US 2014/0066625).
In some embodiments, an immuno-oncology agent is an OX40 agonist. In some embodiments, an OX40 agonist is an agonistic OX40 antibody. In some embodiments, an OX40 antibody is MEDI-6383 or MEDI-6469.
In some embodiments, an immuno-oncology agent is an OX40L antagonist. In some embodiments, an OX40L antagonist is an antagonistic OX40 antibody. In some embodiments, an OX40L antagonist is RG-7888 (WO 2006/029879, U.S. Pat. No. 7,501,496).
In some embodiments, an immuno-oncology agent is a CD40 agonist. In some embodiments, a CD40 agonist is an agonistic CD40 antibody. In some embodiments, an immuno-oncology agent is a CD40 antagonist. In some embodiments, a CD40 antagonist is an antagonistic CD40 antibody. In some embodiments, a CD40 antibody is lucatumumab or dacetuzumab.
In some embodiments, an immuno-oncology agent is a CD27 agonist. In some embodiments, a CD27 agonist is an agonistic CD27 antibody. In some embodiments, a CD27 antibody is varlilumab.
In some embodiments, an immuno-oncology agent is MGA271 (to B7H3) (WO 2011/109400, US 2013/0149236).
In some embodiments, an immuno-oncology agent is abagovomab, adecatumumab, afutuzumab, alemtuzumab, anatumomab mafenatox, apolizumab, atezolimab, avelumab, blinatumomab, BMS-936559, catumaxomab, durvalumab, epacadostat, epratuzumab, indoximod, inotuzumab ozogamicin, intelumumab, ipilimumab, isatuximab, lambrolizumab, MED14736, MPDL3280A, nivolumab, obinutuzumab, ocaratuzumab, ofatumumab, olatatumab, pembrolizumab, pidilizumab, rituximab, ticilimumab, samalizumab, or tremelimumab.
In some embodiments, an immuno-oncology agent is an immunostimulatory agent. For example, antibodies blocking the PD-1 and PD-L1 inhibitory axis can unleash activated tumor-reactive T cells and have been shown in clinical trials to induce durable anti-tumor responses in increasing numbers of tumor histologies, including some tumor types that conventionally have not been considered immunotherapy sensitive. See, e.g., Okazaki, T. et al. (2013) Nat. Immunol. 14, 1212-1218; Zou et al. (2016) Sci. Transl. Med. 8. The anti-PD-1 antibody nivolumab (Opdivo®, Bristol-Myers Squibb, also known as ONO-4538, MDX1106 and BMS-936558), has shown potential to improve the overall survival in patients with RCC who had experienced disease progression during or after prior anti-angiogenic therapy.
In some embodiments, the immunomodulatory therapeutic specifically induces apoptosis of tumor cells. Approved immunomodulatory therapeutics which may be used in the present invention include pomalidomide (Pomalyst®, Celgene); lenalidomide (Revlimid®, Celgene); ingenol mebutate (Picato®, LEO Pharma).
In some embodiments, an immuno-oncology agent is a cancer vaccine. In some embodiments, the cancer vaccine is selected from sipuleucel-T (Provenge®, Dendreon/Valeant Pharmaceuticals), which has been approved for treatment of asymptomatic, or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer; and talimogene laherparepvec (Imlygic®, BioVex/Amgen, previously known as T-VEC), a genetically modified oncolytic viral therapy approved for treatment of unresectable cutaneous, subcutaneous and nodal lesions in melanoma. In some embodiments, an immuno-oncology agent is selected from an oncolytic viral therapy such as pexastimogene devacirepvec (PexaVec/JX-594, SillaJen/formerly Jennerex Biotherapeutics), a thymidine kinase- (TK-) deficient vaccinia virus engineered to express GM-CSF, for hepatocellular carcinoma (NCT02562755) and melanoma (NCT00429312); pelareorep (Reolysin®, Oncolytics Biotech), a variant of respiratory enteric orphan virus (reovirus) which does not replicate in cells that are not RAS-activated, in numerous cancers, including colorectal cancer (NCT01622543); prostate cancer (NCT01619813); head and neck squamous cell cancer (NCT01166542); pancreatic adenocarcinoma (NCT00998322); and non-small cell lung cancer (NSCLC) (NCT 00861627); enadenotucirev (NG-348, PsiOxus, formerly known as ColoAd1), an adenovirus engineered to express a full length CD80 and an antibody fragment specific for the T-cell receptor CD3 protein, in ovarian cancer (NCT02028117); metastatic or advanced epithelial tumors such as in colorectal cancer, bladder cancer, head and neck squamous cell carcinoma and salivary gland cancer (NCT02636036); ONCOS-102 (Targovax/formerly Oncos), an adenovirus engineered to express GM-CSF, in melanoma (NCT03003676); and peritoneal disease, colorectal cancer or ovarian cancer (NCT02963831); GL-ONC1 (GLV-1h68/GLV-1h153, Genelux GmbH), vaccinia viruses engineered to express beta-galactosidase (beta-gal)/beta-glucoronidase or beta-gal/human sodium iodide symporter (hNIS), respectively, were studied in peritoneal carcinomatosis (NCT01443260); fallopian tube cancer, ovarian cancer (NCT 02759588); or CG0070 (Cold Genesys), an adenovirus engineered to express GM-CSF, in bladder cancer (NCT02365818).
In some embodiments, an immuno-oncology agent is selected from JX-929 (SillaJen/formerly Jennerex Biotherapeutics), a TK- and vaccinia growth factor-deficient vaccinia virus engineered to express cytosine deaminase, which is able to convert the prodrug 5-fluorocytosine to the cytotoxic drug 5-fluorouracil; TG01 and TG02 (Targovax/formerly Oncos), peptide-based immunotherapy agents targeted for difficult-to-treat RAS mutations; and TILT-123 (TILT Biotherapeutics), an engineered adenovirus designated: Ad5/3-E2F-delta24-hTNFα-IRES-hIL20; and VSV-GP (ViraTherapeutics) a vesicular stomatitis virus (VSV) engineered to express the glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV), which can be further engineered to express antigens designed to raise an antigen-specific CD8+ T cell response.
In some embodiments, an immuno-oncology agent is a T-cell engineered to express a chimeric antigen receptor, or CAR. The T-cells engineered to express such chimeric antigen receptor are referred to as a CAR-T cells.
CARs have been constructed that consist of binding domains, which may be derived from natural ligands, single chain variable fragments (scFv) derived from monoclonal antibodies specific for cell-surface antigens, fused to endodomains that are the functional end of the T-cell receptor (TCR), such as the CD3-zeta signaling domain from TCRs, which is capable of generating an activation signal in T lymphocytes. Upon antigen binding, such CARs link to endogenous signaling pathways in the effector cell and generate activating signals similar to those initiated by the TCR complex.
For example, in some embodiments the CAR-T cell is one of those described in U.S. Pat. No. 8,906,682, the entirety of each of which is herein incorporated by reference, which discloses CAR-T cells engineered to comprise an extracellular domain having an antigen binding domain (such as a domain that binds to CD19), fused to an intracellular signaling domain of the T cell antigen receptor complex zeta chain (such as CD3 zeta). When expressed in the T cell, the CAR is able to redirect antigen recognition based on the antigen binding specificity. In the case of CD19, the antigen is expressed on malignant B cells. Over 200 clinical trials are currently in progress employing CAR-T in a wide range of indications. [https://clinicaltrials.gov/ct2/results?term=chimeric+antigen+receptors&pg=1].
In some embodiments, an immunostimulatory agent is an activator of retinoic acid receptor-related orphan receptor γ (RORγt). RORγt is a transcription factor with key roles in the differentiation and maintenance of Type 17 effector subsets of CD4+ (Th17) and CD8+ (Tc17) T cells, as well as the differentiation of IL-17 expressing innate immune cell subpopulations such as NK cells. In some embodiments, an activator of RORγt is LYC-55716 (Lycera), which is currently being evaluated in clinical trials for the treatment of solid tumors (NCT02929862).
In some embodiments, an immunostimulatory agent is an agonist or activator of a toll-like receptor (TLR). Suitable activators of TLRs include an agonist or activator of TLR9 such as SD-101 (Dynavax). SD-101 is an immunostimulatory CpG which is being studied for B-cell, follicular and other lymphomas (NCT02254772). Agonists or activators of TLR8 which may be used in the present invention include motolimod (VTX-2337, VentiRx Pharmaceuticals) which is being studied for squamous cell cancer of the head and neck (NCT02124850) and ovarian cancer (NCT02431559).
Other immuno-oncology agents that may be used in the present invention include urelumab (BMS-663513, Bristol-Myers Squibb), an anti-CD137 monoclonal antibody; varlilumab (CDX-1127, Celldex Therapeutics), an anti-CD27 monoclonal antibody; BMS-986178 (Bristol-Myers Squibb), an anti-OX40 monoclonal antibody; lirilumab (IPH2102/BMS-986015, Innate Pharma, Bristol-Myers Squibb), an anti-KIR monoclonal antibody; monalizumab (IPH2201, Innate Pharma, AstraZeneca) an anti-NKG2A monoclonal antibody; andecaliximab (GS-5745, Gilead Sciences), an anti-MMP9 antibody; MK-4166 (Merck & Co.), an anti-GITR monoclonal antibody.
In some embodiments, an immunostimulatory agent is selected from elotuzumab, mifamurtide, an agonist or activator of a toll-like receptor, and an activator of RORγt.
In some embodiments, an immunostimulatory therapeutic is recombinant human interleukin 15 (rhIL-15). rhIL-15 has been tested in the clinic as a therapy for melanoma and renal cell carcinoma (NCT01021059 and NCT01369888) and leukemias (NCT02689453). In some embodiments, an immunostimulatory agent is recombinant human interleukin 12 (rhIL-12). In some embodiments, an IL-15 based immunotherapeutic is heterodimeric IL-15 (hetIL-15, Novartis/Admune), a fusion complex composed of a synthetic form of endogenous IL-15 complexed to the soluble IL-15 binding protein IL-15 receptor alpha chain (IL15:sIL-15RA), which has been tested in Phase 1 clinical trials for melanoma, renal cell carcinoma, non-small cell lung cancer and head and neck squamous cell carcinoma (NCT02452268). In some embodiments, a recombinant human interleukin 12 (rhIL-12) is NM-IL-12 (Neumedicines, Inc.), NCT02544724, or NCT02542124.
In some embodiments, an immuno-oncology agent is selected from those descripted in Jerry L. Adams ET. AL., “Big opportunities for small molecules in immuno-oncology,” Cancer Therapy 2015, Vol. 14, pages 603-622, the content of which is incorporated herein by reference in its entirety. In some embodiments, an immuno-oncology agent is selected from the examples described in Table 1 of Jerry L. Adams ET. AL. In some embodiments, an immuno-oncology agent is a small molecule targeting an immuno-oncoloby target selected from those listed in Table 2 of Jerry L. Adams ET. AL. In some embodiments, an immuno-oncology agent is a small molecule agent selected from those listed in Table 2 of Jerry L. Adams ET. AL.
In some embodiments, an immuno-oncology agent is selected from the small molecule immuno-oncology agents described in Peter L. Toogood, “Small molecule immuno-oncology therapeutic agents,” Bioorganic & Medicinal Chemistry Letters 2018, Vol. 28, pages 319-329, the content of which is incorporated herein by reference in its entirety. In some embodiments, an immuno-oncology agent is an agent targeting the pathways as described in Peter L. Toogood.
In some embodiments, an immuno-oncology agent is selected from those described in Sandra L. Ross et al., “Bispecific T cell engager (BiTE®) antibody constructs can mediate bystander tumor cell killing”, PLoS ONE 12(8): e0183390, the content of which is incorporated herein by reference in its entirety. In some embodiments, an immuno-oncology agent is a bispecific T cell engager (BiTE®) antibody construct. In some embodiments, a bispecific T cell engager (BiTE®) antibody construct is a CD19/CD3 bispecific antibody construct. In some embodiments, a bispecific T cell engager (BiTE®) antibody construct is an EGFR/CD3 bispecific antibody construct. In some embodiments, a bispecific T cell engager (BiTE®) antibody construct activates T cells. In some embodiments, a bispecific T cell engager (BiTE®) antibody construct activates T cells, which release cytokines inducing upregulation of intercellular adhesion molecule 1 (ICAM-1) and FAS on bystander cells. In some embodiments, a bispecific T cell engager (BiTE®) antibody construct activates T cells which result in induced bystander cell lysis. In some embodiments, the bystander cells are in solid tumors. In some embodiments, the bystander cells being lysed are in proximity to the BiTE®-activated T cells. In some embodiment, the bystander cells comprises tumor-associated antigen (TAA) negative cancer cells. In some embodiment, the bystander cells comprise EGFR-negative cancer cells. In some embodiments, an immuno-oncology agent is an antibody which blocks the PD-L1/PD1 axis and/or CTLA4. In some embodiments, an immuno-oncology agent is an ex-vivo expanded tumor-infiltrating T cell. In some embodiments, an immuno-oncology agent is a bispecific antibody construct or chimeric antigen receptors (CARs) that directly connect T cells with tumor-associated surface antigens (TAAs).
Exemplary Immune Checkpoint Inhibitors
In some embodiments, an immuno-oncology agent is an immune checkpoint inhibitor as described herein.
The term “checkpoint inhibitor” as used herein relates to agents useful in preventing cancer cells from avoiding the immune system of the patient. One of the major mechanisms of anti-tumor immunity subversion is known as “T-cell exhaustion,” which results from chronic exposure to antigens that has led to up-regulation of inhibitory receptors. These inhibitory receptors serve as immune checkpoints in order to prevent uncontrolled immune reactions.
PD-1 and co-inhibitory receptors such as cytotoxic T-lymphocyte antigen 4 (CTLA-4, B and T Lymphocyte Attenuator (BTLA; CD272), T cell Immunoglobulin and Mucin domain-3 (Tim-3), Lymphocyte Activation Gene-3 (Lag-3; CD223), and others are often referred to as a checkpoint regulators. They act as molecular “gatekeepers” that allow extracellular information to dictate whether cell cycle progression and other intracellular signaling processes should proceed.
In some embodiments, an immune checkpoint inhibitor is an antibody to PD-1. PD-1 binds to the programmed cell death 1 receptor (PD-1) to prevent the receptor from binding to the inhibitory ligand PDL-1, thus overriding the ability of tumors to suppress the host anti-tumor immune response.
In one aspect, the checkpoint inhibitor is a biologic therapeutic or a small molecule. In another aspect, the checkpoint inhibitor is a monoclonal antibody, a humanized antibody, a fully human antibody, a fusion protein or a combination thereof. In a further aspect, the checkpoint inhibitor inhibits a checkpoint protein selected from CTLA-4, PDL1, PDL2, PD1, B7-H3, B7-H4, BTLA, HVEM, TIM3, GAL9, LAG3, VISTA, KIR, 2B4, CD160, CGEN-15049, CHK 1, CHK2, A2aR, B-7 family ligands or a combination thereof. In an additional aspect, the checkpoint inhibitor interacts with a ligand of a checkpoint protein selected from CTLA-4, PDL1, PDL2, PD1, B7-H3, B7-H4, BTLA, HVEM, TIM3, GAL9, LAG3, VISTA, KIR, 2B4, CD160, CGEN-15049, CHK 1, CHK2, A2aR, B-7 family ligands or a combination thereof. In an aspect, the checkpoint inhibitor is an immunostimulatory agent, a T cell growth factor, an interleukin, an antibody, a vaccine or a combination thereof. In a further aspect, the interleukin is IL-7 or IL-15. In a specific aspect, the interleukin is glycosylated IL-7. In an additional aspect, the vaccine is a dendritic cell (DC) vaccine.
Checkpoint inhibitors include any agent that blocks or inhibits in a statistically significant manner, the inhibitory pathways of the immune system. Such inhibitors may include small molecule inhibitors or may include antibodies, or antigen binding fragments thereof, that bind to and block or inhibit immune checkpoint receptors or antibodies that bind to and block or inhibit immune checkpoint receptor ligands. Illustrative checkpoint molecules that may be targeted for blocking or inhibition include, but are not limited to, CTLA-4, PDL1, PDL2, PD1, B7-H3, B7-H4, BTLA, HVEM, GAL9, LAG3, TIM3, VISTA, KIR, 2B4 (belongs to the CD2 family of molecules and is expressed on all NK, γδ, and memory CD8+ (αβ) T cells), CD160 (also referred to as BY55), CGEN-15049, CHK 1 and CHK2 kinases, A2aR, and various B-7 family ligands. B7 family ligands include, but are not limited to, B7-1, B7-2, B7-DC, B7-H1, B7-H2, B7-H3, B7-H4, B7-H5, B7-H6 and B7-H7. Checkpoint inhibitors include antibodies, or antigen binding fragments thereof, other binding proteins, biologic therapeutics, or small molecules, that bind to and block or inhibit the activity of one or more of CTLA-4, PDL1, PDL2, PD1, BTLA, HVEM, TIM3, GAL9, LAG3, VISTA, KIR, 2B4, CD 160 and CGEN-15049. Illustrative immune checkpoint inhibitors include Tremelimumab (CTLA-4 blocking antibody), anti-OX40, PD-L1 monoclonal Antibody (Anti-B7-H1; MEDI4736), MK-3475 (PD-1 blocker), Nivolumab (anti-PD1 antibody), CT-011 (anti-PD1 antibody), BY55 monoclonal antibody, AMP224 (anti-PDL1 antibody), BMS-936559 (anti-PDL1 antibody), MPLDL3280A (anti-PDL1 antibody), MSB0010718C (anti-PDL1 antibody), and ipilimumab (anti-CTLA-4 checkpoint inhibitor). Checkpoint protein ligands include, but are not limited to PD-L1, PD-L2, B7-H3, B7-H4, CD28, CD86 and TIM-3.
In certain embodiments, the immune checkpoint inhibitor is selected from a PD-1 antagonist, a PD-L1 antagonist, and a CTLA-4 antagonist. In some embodiments, the checkpoint inhibitor is selected from the group consisting of nivolumab (Opdivo®), ipilimumab (Yervoy®), and pembrolizumab (Keytruda®). In some embodiments, the checkpoint inhibitor is selected from nivolumab (anti-PD-1 antibody, Opdivo®, Bristol-Myers Squibb); pembrolizumab (anti-PD-1 antibody, Keytruda®, Merck); ipilimumab (anti-CTLA-4 antibody, Yervoy®, Bristol-Myers Squibb); durvalumab (anti-PD-L1 antibody, Imfinzi®, AstraZeneca); and atezolizumab (anti-PD-L1 antibody, Tecentriq®, Genentech).
In some embodiments, the checkpoint inhibitor is selected from the group consisting of lambrolizumab (MK-3475), nivolumab (BMS-936558), pidilizumab (CT-011), AMP-224, MDX-1105, MEDI4736, MPDL3280A, BMS-936559, ipilimumab, lirlumab, IPH2101, pembrolizumab (Keytruda®), and tremelimumab.
In some embodiments, an immune checkpoint inhibitor is REGN2810 (Regeneron), an anti-PD-1 antibody tested in patients with basal cell carcinoma (NCT03132636); NSCLC (NCT03088540); cutaneous squamous cell carcinoma (NCT02760498); lymphoma (NCT02651662); and melanoma (NCT03002376); pidilizumab (CureTech), also known as CT-011, an antibody that binds to PD-1, in clinical trials for diffuse large B-cell lymphoma and multiple myeloma; avelumab (Bavencio®, Pfizer/Merck KGaA), also known as MSB0010718C), a fully human IgG1 anti-PD-L1 antibody, in clinical trials for non-small cell lung cancer, Merkel cell carcinoma, mesothelioma, solid tumors, renal cancer, ovarian cancer, bladder cancer, head and neck cancer, and gastric cancer; or PDR001 (Novartis), an inhibitory antibody that binds to PD-1, in clinical trials for non-small cell lung cancer, melanoma, triple negative breast cancer and advanced or metastatic solid tumors. Tremelimumab (CP-675,206; Astrazeneca) is a fully human monoclonal antibody against CTLA-4 that has been in studied in clinical trials for a number of indications, including: mesothelioma, colorectal cancer, kidney cancer, breast cancer, lung cancer and non-small cell lung cancer, pancreatic ductal adenocarcinoma, pancreatic cancer, germ cell cancer, squamous cell cancer of the head and neck, hepatocellular carcinoma, prostate cancer, endometrial cancer, metastatic cancer in the liver, liver cancer, large B-cell lymphoma, ovarian cancer, cervical cancer, metastatic anaplastic thyroid cancer, urothelial cancer, fallopian tube cancer, multiple myeloma, bladder cancer, soft tissue sarcoma, and melanoma. AGEN-1884 (Agenus) is an anti-CTLA4 antibody that is being studied in Phase 1 clinical trials for advanced solid tumors (NCT02694822).
In some embodiments, a checkpoint inhibitor is an inhibitor of T-cell immunoglobulin mucin containing protein-3 (TIM-3). TIM-3 inhibitors that may be used in the present invention include TSR-022, LY3321367 and MBG453. TSR-022 (Tesaro) is an anti-TIM-3 antibody which is being studied in solid tumors (NCT02817633). LY3321367 (Eli Lilly) is an anti-TIM-3 antibody which is being studied in solid tumors (NCT03099109). MBG453 (Novartis) is an anti-TIM-3 antibody which is being studied in advanced malignancies (NCT02608268).
In some embodiments, a checkpoint inhibitor is an inhibitor of T cell immunoreceptor with Ig and ITIM domains, or TIGIT, an immune receptor on certain T cells and NK cells. TIGIT inhibitors that may be used in the present invention include BMS-986207 (Bristol-Myers Squibb), an anti-TIGIT monoclonal antibody (NCT02913313); OMP-313M32 (Oncomed); and anti-TIGIT monoclonal antibody (NCT03119428).
In some embodiments, a checkpoint inhibitor is an inhibitor of Lymphocyte Activation Gene-3 (LAG-3). LAG-3 inhibitors that may be used in the present invention include BMS-986016 and REGN3767 and IMP321. BMS-986016 (Bristol-Myers Squibb), an anti-LAG-3 antibody, is being studied in glioblastoma and gliosarcoma (NCT02658981). REGN3767 (Regeneron), is also an anti-LAG-3 antibody, and is being studied in malignancies (NCT03005782). IMP321 (Immutep S.A.) is an LAG-3-Ig fusion protein, being studied in melanoma (NCT02676869); adenocarcinoma (NCT02614833); and metastatic breast cancer (NCT00349934).
Checkpoint inhibitors that may be used in the present invention include OX40 agonists. OX40 agonists that are being studied in clinical trials include PF-04518600/PF-8600 (Pfizer), an agonistic anti-OX40 antibody, in metastatic kidney cancer (NCT03092856) and advanced cancers and neoplasms (NCT02554812; NCT05082566); GSK3174998 (Merck), an agonistic anti-OX40 antibody, in Phase 1 cancer trials (NCT02528357); MEDI0562 (Medimmune/AstraZeneca), an agonistic anti-OX40 antibody, in advanced solid tumors (NCT02318394 and NCT02705482); MEDI6469, an agonistic anti-OX40 antibody (Medimmune/AstraZeneca), in patients with colorectal cancer (NCT02559024), breast cancer (NCT01862900), head and neck cancer (NCT02274155) and metastatic prostate cancer (NCT01303705); and BMS-986178 (Bristol-Myers Squibb) an agonistic anti-OX40 antibody, in advanced cancers (NCT02737475).
Checkpoint inhibitors that may be used in the present invention include CD137 (also called 4-1BB) agonists. CD137 agonists that are being studied in clinical trials include utomilumab (PF-05082566, Pfizer) an agonistic anti-CD137 antibody, in diffuse large B-cell lymphoma (NCT02951156) and in advanced cancers and neoplasms (NCT02554812 and NCT05082566); urelumab (BMS-663513, Bristol-Myers Squibb), an agonistic anti-CD137 antibody, in melanoma and skin cancer (NCT02652455) and glioblastoma and gliosarcoma (NC T02658981).
Checkpoint inhibitors that may be used in the present invention include CD27 agonists. CD27 agonists that are being studied in clinical trials include varlilumab (CDX-1127, Celldex Therapeutics) an agonistic anti-CD27 antibody, in squamous cell head and neck cancer, ovarian carcinoma, colorectal cancer, renal cell cancer, and glioblastoma (NCT02335918); lymphomas (NCT01460134); and glioma and astrocytoma (NCT02924038).
Checkpoint inhibitors that may be used in the present invention include glucocorticoid-induced tumor necrosis factor receptor (GITR) agonists. GITR agonists that are being studied in clinical trials include TRX518 (Leap Therapeutics), an agonistic anti-GITR antibody, in malignant melanoma and other malignant solid tumors (NCT01239134 and NCT02628574); GWN323 (Novartis), an agonistic anti-GITR antibody, in solid tumors and lymphoma (NCT 02740270); INCAGN01876 (Incyte/Agenus), an agonistic anti-GITR antibody, in advanced cancers (NCT02697591 and NCT03126110); MK-4166 (Merck), an agonistic anti-GITR antibody, in solid tumors (NCT02132754) and MEDI1873 (Medimmune/AstraZeneca), an agonistic hexameric GITR-ligand molecule with a human IgG1 Fc domain, in advanced solid tumors (NCT02583165).
Checkpoint inhibitors that may be used in the present invention include inducible T-cell co-stimulator (ICOS, also known as CD278) agonists. ICOS agonists that are being studied in clinical trials include MEDI-570 (Medimmune), an agonistic anti-ICOS antibody, in lymphomas (NCT02520791); GSK3359609 (Merck), an agonistic anti-ICOS antibody, in Phase 1 (NCT02723955); JTX-2011 (Jounce Therapeutics), an agonistic anti-ICOS antibody, in Phase 1 (NCT02904226).
Checkpoint inhibitors that may be used in the present invention include killer IgG-like receptor (KIR) inhibitors. KIR inhibitors that are being studied in clinical trials include lirilumab (IPH2102/BMS-986015, Innate Pharma/Bristol-Myers Squibb), an anti-KIR antibody, in leukemias (NCT01687387, NCT02399917, NCT02481297, NCT02599649), multiple myeloma (NCT02252263), and lymphoma (NCT01592370); IPH2101 (1-7F9, Innate Pharma) in myeloma (NCT01222286 and NCT01217203); and IPH4102 (Innate Pharma), an anti-KIR antibody that binds to three domains of the long cytoplasmic tail (KIR3DL2), in lymphoma (NCT02593045).
Checkpoint inhibitors that may be used in the present invention include CD47 inhibitors of interaction between CD47 and signal regulatory protein alpha (SIRPa). CD47/SIRPa inhibitors that are being studied in clinical trials include ALX-148 (Alexo Therapeutics), an antagonistic variant of (SIRPa) that binds to CD47 and prevents CD47/SIRPa-mediated signaling, in phase 1 (NCT03013218); TTI-621 (SIRPa-Fc, Trillium Therapeutics), a soluble recombinant fusion protein created by linking the N-terminal CD47-binding domain of SIRPa with the Fc domain of human IgG1, acts by binding human CD47, and preventing it from delivering its “do not eat” signal to macrophages, is in clinical trials in Phase 1 (NCT02890368 and NCT02663518); CC-90002 (Celgene), an anti-CD47 antibody, in leukemias (NCT02641002); and Hu5F9-G4 (Forty Seven, Inc.), in colorectal neoplasms and solid tumors (NCT02953782), acute myeloid leukemia (NCT02678338) and lymphoma (NCT02953509).
Checkpoint inhibitors that may be used in the present invention include CD73 inhibitors. CD73 inhibitors that are being studied in clinical trials include MEDI9447 (Medimmune), an anti-CD73 antibody, in solid tumors (NCT02503774); and BMS-986179 (Bristol-Myers Squibb), an anti-CD73 antibody, in solid tumors (NCT02754141).
Checkpoint inhibitors that may be used in the present invention include agonists of stimulator of interferon genes protein (STING, also known as transmembrane protein 173, or TMEM173). Agonists of STING that are being studied in clinical trials include MK-1454 (Merck), an agonistic synthetic cyclic dinucleotide, in lymphoma (NCT03010176); and ADU-S100 (MIW815, Aduro Biotech/Novartis), an agonistic synthetic cyclic dinucleotide, in Phase 1 (NCT02675439 and NCT03172936).
Checkpoint inhibitors that may be used in the present invention include CSF1R inhibitors. CSF1R inhibitors that are being studied in clinical trials include pexidartinib (PLX3397, Plexxikon), a CSF1R small molecule inhibitor, in colorectal cancer, pancreatic cancer, metastatic and advanced cancers (NCT02777710) and melanoma, non-small cell lung cancer, squamous cell head and neck cancer, gastrointestinal stromal tumor (GIST) and ovarian cancer (NCT02452424); and IMC-CS4 (LY3022855, Lilly), an anti-CSF-1R antibody, in pancreatic cancer (NCT03153410), melanoma (NCT03101254), and solid tumors (NCT02718911); and BLZ945 (4-[2((1R,2R)-2-hydroxycyclohexylamino)-benzothiazol-6-yloxyl]-pyridine-2-carboxylic acid methylamide, Novartis), an orally available inhibitor of CSF1R, in advanced solid tumors (NCT02829723).
Checkpoint inhibitors that may be used in the present invention include NKG2A receptor inhibitors. NKG2A receptor inhibitors that are being studied in clinical trials include monalizumab (IPH2201, Innate Pharma), an anti-NKG2A antibody, in head and neck neoplasms (NCT02643550) and chronic lymphocytic leukemia (NCT02557516).
In some embodiments, the immune checkpoint inhibitor is selected from nivolumab, pembrolizumab, ipilimumab, avelumab, durvalumab, atezolizumab, or pidilizumab.
EXEMPLIFICATION
As depicted in the Examples below, in certain exemplary embodiments, compounds are prepared according to the following general procedures. It will be appreciated that, although the general methods depict the synthesis of certain compounds of the present invention, the following general methods, and other methods known to one of ordinary skill in the art, can be applied to all compounds and subclasses and species of each of these compounds, as described herein.
Example 1. Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay
Equal volumes of His-tagged CRBN-DDB1 complex (56 nM) was mixed with Eu-cryptate labeled Anti-6HIS-monoclonal antibody (50× dilution from the commercial stock solution, Vender: Cisbio, Cat. #61HI2KLA) in a final buffer containing 20 mM HEPES pH 7.0, 150 mM NaCl, 0.005% Tween-20. The solution was then mixed with Cy5-labeled thalidomide (final 8 nM) and various concentrations of compounds (a serial 3-fold dilution with the top concentration 200 uM). The mixture were incubated at room temperature for 1 hour. FRET signals were measured on an EnVision plate reader (Perkin Elmer) by exciting at 340 nm and recording emission at both 615 nm as no FRET control and 665 nm as the FRET signals with a 60 microsecond delay. FRET efficiency was calculated as the ratio of fluorescent signals at 665 nM/615 nM. Quantitative loss of FRET efficiency as a function of compound concentrations was fitted by a four-parameter Logistic Function using GraphPad Prism 7.0 and the IC50 values were reported for each compound.
Example 2. Fluorescence Polarization (FP) Assay
Untagged CRBN-DDB1 complex (final 50 nM) was mixed with Cy5-labeled thalidomide (final 20 nM) and various concentrations of compounds (a serial 3-fold dilution with the top concentration of 200 uM). The final solution contained 50 mM HEPES, 200 mM NaCl and 2 mM DTT, pH 7.5. The mixtures were incubated at room temperature for 10 min. The FP signals were recorded on an EnVision plate reader (Perkin Elmer) using the following settings: Excitation Light (%): 100; Measurement Height: 12; G-Factor: 1; Detector Gain 1: 500; Detector Gain 2: 500; Flash Number: 100. Dose-dependent loss of FP signals was fitted by four-parameter Logistic Function using GraphPad Prism 7.0 and the IC50 values were reported for each compound.
While we have described a number of embodiments of this invention, it is apparent that our basic examples may be altered to provide other embodiments that utilize the compounds and methods of this invention. Therefore, it will be appreciated that the scope of this invention is to be defined by the appended claims rather than by the specific embodiments that have been represented by way of example.