Protein degraders and uses thereof

Abstract

The present invention provides compounds, compositions thereof, and methods of using the same for the targeted degradation of proteins, and the treatment of target protein-mediated disorders.

Description

PROTEIN DEGRADERS AND USES THEREOFTECHNICAL FIELD OF THE INVENTION

[0001] 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

[0002] 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.

[0003] 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.

[0004] 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 (EVIiDs), e.g. thalidomide, to CRBN has now been associated with teratogenicity and also the cytotoxicity of EVIiDs, 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 EVIiD 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).

[0005] 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.

[0006] 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.

[0007] 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 JS Jr., Chembiochem, 2005, 6(l):40-46).

[0008] 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 targetted and modulated withspecificity 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

[0009] 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.

[0010] 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.

[0011] 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; andUBM is a ubiquitin binding moiety capable of binding to a ubiquitin ligase such as an E3 Ubiquitin Ligase (e.g., cereblon).

[0012] 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:Ior a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described herein.

[0013] It has also 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":I"or a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described herein.

[0014] It has also 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 II-A:II-Aor a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described herein.

[0015] It has also 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 II"-A:II"-Aor a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described herein.

[0016] It has also 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 II-B:II-Bor a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described herein.

[0017] It has also 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 II"-B:II"-Bor a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described herein.

[0018] 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.

[0019] 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 EMBODIMENTS1. General Description of Certain Embodiments of the Invention:

[0020] Compounds of the present invention, and compositions thereof, are useful for the modulation of targeted ubiquitination.

[0021] 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.

[0022] In certain embodiments the present invention provides a compound of formula I:Ior a pharmaceutically acceptable salt thereof, wherein:X1a bivalent moiety selected from a covalent bond, -CH2- -C(O)-, -C(S)-,R is hydrogen, deuterium, halogen, -CN, OR, SR, -S(0)R, -S(0)2R, -NR2, or an optionally substituted Ci-4 aliphatic;each R2is independently hydrogen, -R6, halogen, -CN, -NO2, -OR, -SR, - R2, -S(0)2R, -S(0)2R2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;RingRing B is a fused ring selected from 6-membered aryl containing 0-2 nitrogen atoms, 5 to 7- membered partially saturated carbocyclyl, 5 to 7-membered partially saturated heterocyclyl with 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur, or 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur;R3is selected from hydrogen, halogen, -OR, -N(R)2, or -SR;each R4is independently hydrogen, -R6, halogen, -CN, -NO2, -OR, -SR, - R2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;R5is hydrogen, C1-4 aliphatic, or -CN;each R6is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -N(R)-, -S-, -OC(O)-, -C(0)0-, -C(O)-, -S(O)-, -S(0)2-, -N(R)S(0)2-, -S(0)2N(R)-, -N(R)C(0)-,- -, -OC(0)N(R)-, -N(R)C(0)0-,, 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, and sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partiallyunsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and 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 nitrogen, oxygen, or sulfur;TBM is a target binding moiety;m is 0, 1, 2, 3 or 4;each of n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, or an optionally substituted group selected from Ci-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are 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, and sulfur.

[0023] In certain embodiments, the present invention provides a compound of formula I':I'or a pharmaceutically acceptable salt thereof, wherein:X1is a bivalent moiety selected from a covalent bond, -CH2- -C(O)-, -C(S)-, orR1is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(0)R, -S(0)2R, -NR2, or an optionally substituted Ci-4 aliphatic;each R2is independently hydrogen, -R6, halogen, -CN, -N02, -OR, -SR, -NR2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0)NR2,-C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;Ring A is a bi- or tricy wherein Ring B is other than imidazo or benzo, ein Ring B is other than benzo, wherein Ring B is other than benzwherein Ring B is other than benzo,Ring B is a fused ring selected from 6-membered aryl containing 0-2 nitrogen atoms, 5 to 7- membered partially saturated carbocyclyl, 5 to 7-membered partially saturated heterocyclyl with 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur, or 5- membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur;R3is selected from hydrogen, halogen, -OR, -N(R)2, or -SR;each R4is independently hydrogen, -R6, halogen, -CN, -N02, -OR, -SR, - R2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;R5is hydrogen, Ci-4 aliphatic, or -CN;each R6is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -N(R)-, - S-, -OC(O)-, -C(0)0-, -C(O)-, -S(O)-, -S(0)2-, -N(R)S(0)2-, -S(0)2N(R)-, -N(R)C(0)-, -n nC(0)N(R)-, -O -, N(R)C(0)0-,, 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, and sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1 -2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and 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 nitrogen, oxygen, or sulfur;TBM is a target binding moiety;m is 0, 1, 2, 3 or 4;each of n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, or an optionally substituted group selected from Ci-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are 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, and sulfur.

[0024] In certain embodiments, the present invention provides a compound of formula I":Ior a pharmaceutically acceptable salt thereof, wherein:X1is a bivalent moiet selected from a covalent bond, -C(R)2- -C(O)-, -C(S)-, -P(0)(OR)-, -X2is a carbon atom or silicon atom;X3is a bivalent moiety selected from -C(R)2- -N(R)-, -CF2- -CHF-, -S-, or -0-;X4is a bivalent moiety selected from a covalent bond or -C(R)2-;— is a single bond or double bond;R1is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(0)R, -S(0)2R, - R2, -P(0)(OR)2, -P(0)( R2)OR, -P(0)( R2)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, an optionally substituted C 1-4 aliphatic, or:R1and X1or X4are 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 nitrogen, oxygen, or sulfur; each R2is independently hydrogen, deuterium, -R6, halogen, -CN, -N02, -OR, -SR, -NR2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0)NR2, -C(0)N(R)OR, -OC(0)R, -OC(0)NR2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0)NR2, -N(R)S(0)2R, -N(R)S(0)2NR2, -P(0)(OR)2, -P(0)(NR2)OR, or -P(0)(NR2)2;whereinRing B is a fused ring selected from 6-membered aryl containing 0-3 nitrogen atoms, 5 to 7- membered partially saturated carbocyclyl, 5 to 7-membered partially saturated heterocyclyl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5 -membered heteroaryl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur;R3is selected from hydrogen, deuterium, halogen, -CN, -N02, -OR, - R2, -SR, -S(0)2R, -S(0)2R2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0) R(OR), -OC(0)R, -OC(0) R2, -OP(0)(OR)2, -OP(0)( R2)2, -OP(0)(OR) R2, -N(R)C(0)R,-N(R)C(0)OR, -N(R)C(0) R2, -N(R)S(0)2R, -N(R)S(0)2NR2, -N(R)P(0)(OR)2, -N(R)P(0)(OR) R2, -P(0)(OR)2, -P(0)( R2)OR, -P(0)( R2)2, -Si(OH)2R, -Si(OH)(R)2, or -Si(R)3;each R4is independently hydrogen, deuterium, -R6, halogen, -S(0)2R, -S(0)2R2;-S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -P(0)(OR)2, -P(0)( R2)OR, or -P(0)( R2)2;R5is hydrogen, deuterium, an optionally substituted C1-4 aliphatic, or -CN;each R6is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring 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;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -N(R)- , -Si(R)2- -Si(OH)(R)-, -Si(OH)2- -P(0)(OR)-, -P(0)(R)-, -P(0)( R2)-, -S-, - OC(O)-, -C(0)0- -C(O)-, -S(O)-, -S(0)2- -N(R)S(0)2- -S(0)2N(R)-,- - -C(0)N(R)-, -OC(0)N(R) -N(R)C(0)0-wherein:each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, an 8-10 membered bicyclic arylenyl, a 3-8 membered saturated or partially unsaturated carbocyclylenyl, a 6-11 membered saturated or partially unsaturated spiro carbocyclylenyl, a 5-12 membered bridged or unbridged bicyclic saturated or partially unsaturated carbocyclylenyl, a 4-10 membered saturated or partially unsaturated heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 6-11 membered saturated or partially unsaturated spiroheterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 5-12 membered bridged or unbridged bicyclic saturated or partially unsaturated heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, or an 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur;TBM is a target binding moiety;m is 0, 1, 2, 3 or 4;each of n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, deuterium, or an optionally substituted group selected from Ci- 6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are 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, and sulfur.

[0025] Where a point of attachment ofis depicted on Ring B, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment ofmay be on Ring A and may also be at any available carbon or nitrogen atom onRing A including the ring to which Ring B is fused. Whereis attached to anitrogen atom bound to R4or R5R4or R5is absent andtakes the lace of the4 or R5group.and — takes the place of the R group. By means of example and for the purpose of clarity, whenis attached to Ring B, Ring A is whenis attached to Ring A, Ring A is whend to a nitrogen atom bound to R4, Ring A iswhenis attached to a nitrogen atom bound to R5, Ring A isis attached to a carbon atom bound to R3, Ring

[0026] Where a point of attachment of -(R2)nis depicted on Ring B, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment of -(R2)nmay be on Ring A and may also be at any available boron, carbon, nitrogen, or silicon atom on Ring A including the ring to which Ring B is fused. Where -R2is attached to a nitrogen atom bound to R4or R5, R4or R5is absent and -R2takes the place of the R4or R5group. Where -R2is attached to a carbon atom bound to R3, R3is absent and -R2takes the place of the R3group.

[0027] In certain embodiments, the present invention provides a compound of Formula II-A:II-Aor a pharmaceutically acceptable salt thereof, whereina bivalent moiety selected from a covalent bond, -CH2- -C(O)-, -C(S)-,is hydrogen, deuterium, halogen, -CN, OR, SR, -S(0)R, -S(0)2R, -NR2, or an optionally substituted C1-4aliphatic;each R2is independently hydrogen, -R4, halogen, -CN, -NO2, -OR, -SR, - R2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;Ring B is selected from a 6-membered aryl containing 0-2 nitrogen atoms or a 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R3is independently hydrogen, -R4, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0)NR2, -C(0)N(R)OR, -OC(0)R, -OC(0)NR2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0)NR2, or -N(R)S(0)2R;each R4is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatomsindependently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;R5is hydrogen, C1-4aliphatic, or -CN;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -N(R)-, - S-, -OC(O)-, -C(0)0-, -C(O)-, -S(O)-, -S(0)2-, -N( -, -S(0)2N(R -, -N(R)C(0)-, --, -OC(0)N(R)-, -N(R)C(0)0-,, 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, and sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1 -2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered heteroaryl enyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroaryl enyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;TBM is a target binding moiety;m is 0, 1, or 2;n is 0, 1, 2, 3, or 4;p is 0 or 1, wherein when p is 0, the bond connecting Ring A and Ring B is connected toeach of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, or an optionally substituted group selected from Ci-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are 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, and sulfur.

[0028] In certain embodiments, the present invention provides a compound of formula II'-A:II'-Aor a pharmaceutically acceptable salt thereof, wherein:X1a bivalent moiety selected from a covalent bond, -CH2- -C(O)-, -C(S)-,R is hydrogen, deuterium, halogen, -CN, OR, SR, -S(0)R, -S(0)2R, -NR2, or an optionally substituted Ci-4 aliphatic;Ring - or bicyclic ring selected fromeach R2is independently hydrogen, -R4, halogen, -CN, -NO2, -OR, -SR, - R2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;Ring B is selected from a 6-membered aryl containing 0-2 nitrogen atoms or a 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R3is independently hydrogen, -R4, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0)NR2, -C(0)N(R)OR, -OC(0)R, -OC(0)NR2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0)NR2, or -N(R)S(0)2R;each R4is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatomsindependently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;R5is hydrogen, C1-4aliphatic, or -CN;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -N(R)-, - S-, -OC(O)-, -C(0)0-, -C(O)-, -S(O)-, -S(0)2-, -N( -, -S(0)2N(R -, -N(R)C(0)-, --, -OC(0)N(R)-, -N(R)C(0)0-,, 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, and sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1 -2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered heteroaryl enyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroaryl enyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;TBM is a target binding moiety;m is 0, 1, or 2;n is 0, 1, 2, 3, or 4;p is 0 or 1, wherein when p is 0, the bond connecting Ring A and Ring B is connected toeach of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, or an optionally substituted group selected from Ci-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are 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, and sulfur.

[0029] In certain embodiments, the present invention provides a compound of Formula II"-A:II"-Aor a pharmaceutically acceptable salt thereof, wherein:X1is ivalent moiety selected from a covalent bond, -C(R)2- -C(O)-, -C(S)-, -P(0)(OR)-, -X2is a carbon atom or silicon atom;X3is a bivalent moiety selected from -C(R)2- -N(R)-, -CF2- -CHF-, -S-, or -0-;X4is a bivalent moiety selected from a covalent bond or -C(R)2-;— is a single bond or double bond;R1is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(0)R, -S(0)2R, - R2, -P(0)(OR)2, -P(0)( R2)OR, -P(0)( R2)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, an optionally substituted Ci-4 aliphatic, or:R1and X1or X4are 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 nitrogen, oxygen, or sulfur;each R2is independently hydrogen, deuterium, -R6, halogen, -CN, -N02, -OR, -SR, - R2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, -S(0)2R, -S(0)2R2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, -N(R)S(0)2R, -N(R)S(0)2R2, -P(0)(OR)2, -P(0)( R2)OR, or -P(0)( R2)2;Ring B is selected from a 6-membered aryl containing 0-3 nitrogen atoms or a 5-membered heteroaryl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur;each R3is selected from hydrogen, deuterium, halogen, -CN, -NO2, -OR, - R2, -SR, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0) R(OR), -OC(0)R, -OC(0) R2, -OP(0)(OR)2, -OP(0)( R2)2, -OP(0)(OR) R2, -N(R)C(0)R, -N(R)C(0)OR, -N(R)C(0) R2, -N(R)S(0)2R, -N(R)S(0)2NR2, -N(R)P(0)(OR)2, -N(R)P(0)(OR) R2, -P(0)(OR)2, -P(0)( R2)OR, -P(0)( R2)2, -Si(OH)2R, -Si(OH)(R)2, or -Si(R)3;each R4is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;R5is hydrogen, deuterium, an optionally substituted C1-4 aliphatic, or -CN;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -N(R)- , -Si(R)2- -Si(OH)(R)-, -Si(OH)2- -P(0)(OR)-, -P(0)(R)-, -P(0)(NR2)-, -S-, - OC(O)-, -C(0)0- -C(O)-, -S(O)-, -S(0)2- -N(R) - -S(0)2N(R)- -N(R)C(0)-, --, -OC(0)N(R) -N(R)C(0)0-, wherein:each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, an 8-10 membered bicyclic arylenyl, a 3-8 membered saturated or partially unsaturated carbocyclylenyl, a 6-1 1 membered saturated or partially unsaturated spiro carbocyclylenyl, a 5-12 membered bridged or unbridged bicyclic saturated or partially unsaturated carbocyclylenyl, a 4-10 membered saturated or partially unsaturated heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 6-1 1 membered saturated or partially unsaturated spiroheterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 5-12 membered bridged or unbridged bicyclic saturated or partially unsaturated heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 5-6 membered heteroaryl enyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, or an 8-10 membered bicyclic heteroaryl enyl having 1-5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur;TBM is a target binding moiety;m is 0, 1, or 2;n is 0, 1, 2, 3, or 4;p is 0 or 1, wherein when p is 0, the bond connecting Ring A and Ring B is connected toeach of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, or an optionally substituted group selected from Ci-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are 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, and sulfur.

[0030] In certain embodiments, the present invention provides a compound of Formula II-B:II-Barmaceutically acceptable salt thereof, wherein:a bivalent moiety selected from a covalent bond, -CH2- -C(O)-, -C(S)-,is hydrogen, deuterium, halogen, -CN,-S(0)R, -S(0)2R, -NR2, or an optionally substituted C1-4aliphatic;Ring A is a mono- or bicyclic ring selected fromm H each R2is independently hydrogen, -R4, halogen, -CN, -N02, -OR, -SR, -NR2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0)NR2, -C(0)N(R)OR, -OC(0)R, -OC(0)NR2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0)NR2, or -N(R)S(0)2R;Ring B is selected from a 6-membered aryl containing 0-2 nitrogen atoms or a 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur;each R3is independently hydrogen, -R4, halogen, -CN, -NO2, -OR, -SR, - R2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;each R4is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;R5is hydrogen, C1-4 aliphatic, or -CN;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -N(R)-, - S-, -OC(O)-, -C(0)0-, -C(O)-, -S(O)-, -S(0)2-, -N( -, -S(0)2N(R -, -N(R)C(0)-, --, -OC(0)N(R)-, -N(R)C(0)0-,, 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, and sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered heteroaryl enyl having 1-4 heteroatoms independentlyselected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;TBM is a target binding moiety;m is 0, 1, or 2;n is 0, 1, 2, 3, or 4;p is 0 or 1;each of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, or an optionally substituted group selected from Ci-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are 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, and sulfur.

[0031] In certain embodiments, the present invention provides a compound of formula II'-B:II'-Bor a pharmaceutically acceptable salt thereof, wherein:is a bivalent moiety selected from a covalent bond, -CH2- -C(O)-, -C(S)-, oris hydrogen, deuterium, halogen, -CN, -C OR, SR, -S(0)R, -S(0)2R, -NR2, or an optionally substituted Ci-4 aliphatic;Ringeach R2is independently hydrogen, -R4, halogen, -CN, -NO2, -OR, -SR, - R2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;Ring B is selected from a 6-membered aryl containing 0-2 nitrogen atoms or a 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R3is independently hydrogen, -R4, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0)NR2, -C(0)N(R)OR, -OC(0)R, -OC(0)NR2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0)NR2, or -N(R)S(0)2R;each R4is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;R5is hydrogen, C1-4 aliphatic, or -CN;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -N(R)-, - S-, -OC(O)-, -C(0)0-, -C(O)-, -S(O)-, -S(0)2-, -N( -, -S(0)2N(R -, -N(R)C(0)-, --N(R)C(0)0-,, 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, and sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and 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 nitrogen, oxygen, or sulfur;TBM is a target binding moiety;m is 0, 1, or 2;n is 0, 1, 2, 3, or 4;p is 0 or 1;each of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, or an optionally substituted group selected from Ci-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatomsindependently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are 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, and sulfur.

[0032] In certain embodiments, the present invention provides a compound of Formula II"-B:II"-Bor a pharmaceutically acceptable salt thereof, wherein:X1is ivalent moiety selected from a covalent bond, -C(R)2- -C(O)-, -C(S)-, -P(0)(OR)-, -X2is a carbon atom or silicon atom;X3is a bivalent moiety selected from -C(R)2- -N(R)-, -CF2- -CHF-, -S-, or -0-;X4is a bivalent moiety selected from a covalent bond or -C(R)2-;— is a single bond or double bond;R1is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(0)R, -S(0)2R, - R2, -P(0)(OR)2, -P(0)( R2)OR, -P(0)( R2)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, an optionally substituted Ci-4 aliphatic, or:R1and X1or X4are 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 nitrogen, oxygen, or sulfur;each R2is independently hydrogen, deuterium, -R6, halogen, -CN, -NO2, -OR, -SR, - R2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, -N(R)S(0)2R, -N(R)S(0)2R2, -P(0)(OR)2, -P(0)( R2)OR, or -P(0)( R2)2;Ring B is selected from a 6-membered aryl containing 0-3 nitrogen atoms or a 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R3is selected from hydrogen, deuterium, halogen, -CN, -N02, -OR, -NR2, -SR, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0)NR2, -C(0)NR(OR), -OC(0)R, -OC(0)NR2, -OP(0)(OR)2, -OP(0)(NR2)2, -OP(0)(OR)NR2, -N(R)C(0)R, -N(R)C(0)OR, -N(R)C(0)NR2, -N(R)S(0)2R, -N(R)S(0)2NR2, -N(R)P(0)(OR)2,-N(R)P(0)(OR) R2, -P(0)(OR)2, -P(0)( R2)OR, -P(0)( R2)2, -Si(OH)2R, -Si(OH)(R)2, or -Si(R)3;each R4is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;R5is hydrogen, deuterium, an optionally substituted Ci-4 aliphatic, or -CN;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -N(R)- , -Si(R)2- -Si(OH)(R)-, -Si(OH)2- -P(0)(OR)-, -P(0)(R)-, -P(0)( R2)-, -S-, - OC(O)-, -C(0)0- -C(O)-, -S(O)-, -S(0)2- -N(R) - -S(0)2N(R)- -N(R)C(0)-, -each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, an 8-10 membered bicyclic arylenyl, a 3-8 membered saturated or partially unsaturated carbocyclylenyl, a 6-11 membered saturated or partially unsaturated spiro carbocyclylenyl, a 5-12 membered bridged or unbridged bicyclic saturated or partially unsaturated carbocyclylenyl, a 4-10 membered saturated or partially unsaturated heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 6-11 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 5-12 membered bridged or unbridged bicyclic saturated or partially unsaturated heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 5-6 memberedheteroarylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, or an 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur;TBM is a target binding moiety;m is 0, 1, or 2;n is 0, 1, 2, 3, or 4;p is 0 or 1;each of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, deuterium, or an optionally substituted group selected from Ci- 6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are 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, and sulfur.

[0033] Where a point of attachment ofis depicted on Ring A, it is intended, and one of ordinary skill in the art would appreciate, that the point of attachment ofmay be at any available carbon or nitrogen atom on Ring A. Whereis attached to a nitrogen atom bound to R3or R5, R3or R5is absent andtakes the place of the R or R group.

[0034] In certain embodiments, the present invention provides a compound of Formula III- A, III-B, or III-C:III-AIII-Cor a pharmaceutically acceptable salt thereof, wherein L and TBM are as defined above and described herein, and wherein each of the variables R1, R2, R4, R5, R10, R11, R14, R17, W1, W2, X and n is as d / 197051 which is herein incorporated by reference in its entiretyand wherein is attached to R1, the ring formed byat the site of attachment of R12as defined in WO 2017 / 197051 suchthe place of the R12substituent.2. Compounds and Definitions:

[0035] 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, 75thEd. Additionally, general principles of organic chemistry are described in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry", 5thEd., Ed. : Smith, M B. and March, J., John Wiley & Sons, New York: 2001, the entire contents of which are hereby incorporated by reference.

[0036] 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 limite to, linear or branched, substituted or unsubstituted alkyl, alkenyl, alkynyl groups and hybrids thereof such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cy cl oalkyl) alkenyl .

[0037] 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 bondconnecting 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:

[0038] The term "lower alkyl" refers to a C1-4straight or branched alkyl group. Exemplary lower alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tert-butyl.

[0039] The term "lower haloalkyl" refers to a C1-4straight or branched alkyl group that is substituted with one or more halogen atoms.

[0040] 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 quaternizedform of any basic nitrogen or; a substitutable nitrogen of a heterocyclic ring, for example N (as in 3,4-dihydro-2H-pyrrolyl), H (as in pyrrolidinyl) or R+(as in N-substituted pyrrolidinyl)).

[0041] The term "unsaturated," as used herein, means that a moiety has one or more units of unsaturation.

[0042] As used herein, the term "bivalent Ci-8(or Ci-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.

[0043] 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.

[0044] 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.m "cyclopropylenyl" refers to a bivalent cyclopropyl group of

[0046] The term "halogen" means F, CI, Br, or I.

[0047] 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.

[0048] 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]-l,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.

[0049] 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), H (as in pyrrolidinyl), or+R (as in N-substituted pyrrolidinyl).

[0050] 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, withoutlimitation, 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.

[0051] 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.

[0052] 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.

[0053] Suitable monovalent substituents on a substitutable carbon atom of an "optionally substituted" group are independently halogen; -(CH2)o-4R°; -(CH2)0-4OR°; -0(CH2)o-4R°, -O- (CH2)o-4C(0)OR°; -(CH2)0-4CH(OR°)2; -(CH2)0^SR°; -(CH2)0^Ph, which may be substituted with R°;which may be substituted with R°; -CH=CHPh, which may besubstituted with R°; -(CH2)o-40(CH2)o-i-pyridyl which may be substituted with R°; -N02; -CN; -N3; -(CH2)o-4N(R°)2; -(CH2)o-4N(R0)C(0)R°; -N(R°)C(S)R°; -(CH2)o-4N(R0)C(0) R°2; -N(R°)C(S) R°2; -(CH2)0-4N(R°)C(O)OR°; -N(R°)N(R°)C(0)R°; -N(R°)N(R°)C(0) R°2; -N(R°)N(R°)C(0)OR°; -(CH2)0-4C(O)R°; -C(S)R°; -(CH2)0-4C(O)OR°; -(CH2)0-4C(O)SR°; -(CH2)o^C(0)OSiR°3; -(CH2)0-4OC(O)R°; -OC(O)(CH2)0-4SR°; -SC(S)SR°; -(CH2)o-4SC(0)R°; -(CH2)0-4C(O) R°2; -C(S) R°2; -C(S)SR°; -(CH2)0-4OC(O) R°2; -C(0)N(OR°)R°; -C(0)C(0)R°; -C(0)CH2C(0)R°; -C(NOR°)R°; -(CH2)0^SSR°; -(CH2)0-4S(0)2R°; -(CH2)o^S(0)2OR°; -(CH2)0-4OS(O)2R°; -S(0)2R°2; -(CH2)<MS(0)R°; -N(R°)S(0)2R°2; -N(R°)S(0)2R°; -N(OR°)R°; -C( H) R°2; -P(0)2R°; -P(0)R°2; -OP(0)R°2; -OP(0)(OR°)2; -SiR°3;straight or branched alkylene)0-N(R°)2; or -(Ci_4straight or branched alkylene)C(0)0-N(R°)2, wherein each R° may be substituted as defined below and is independently hydrogen, Ci-6aliphatic, -CH2Ph, -0(CH2)o-iPh, -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.

[0054] 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)o-2R*, -(haloR"), -(CH2)o-2OH, -(CH2)0-2OR", -(CH2)0-2CH(OR")2; -O(haloR'), -CN, -N3, -(CH2)0-2C(0)R', -(CH2)o-2C(0)OH, -(CH2)o-2C(0)OR', -(CH2)0-2SR', -(CH2)0-2SH, -(CH2)0-2NH2, - (CH2)o-2NHRe, -(CH2)o-2NR'2, -N02, -SiR'3, -OSiR'3, -C(0)SR* -(Ci_4straight or branched alkylene)C(0)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 fromaliphatic, - CH2Ph, -0(CH2)o-iPh, 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 =0 and =S.

[0055] Suitable divalent substituents on a saturated carbon atom of an "optionally substituted" group include the following: =0, =S, =NNR*2, =N HC(0)R*, =N HC(0)OR*, =N HS(0)2R*, = R*, =NOR*, -0(C(R*2))2-30- or -S(C(R*2))2-3S- wherein each independent occurrence of R*is selected from hydrogen, Ci-6aliphatic 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: -0(CR*2)2- 3O-, wherein each independent occurrence of R*is selected from hydrogen, Ci-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.

[0056] Suitable substituents on the aliphatic group of R*include halogen, -R", -(haloR"), -OH, -OR', -O(haloR'), -CN, -C(0)OH, -C(0)OR', - H2, -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, -0(CH2)o-iPh, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0057] Suitable substituents on a substitutable nitrogen of an "optionally substituted" group include -R†, - R†2, -C(0)R†, -C(0)OR†, -C(0)C(0)R†, -C(0)CH2C(0)R†, -S(0)2R†, -S(0)2R†2, -C(S) R†2, -C( H) R†2, or -N(R†)S(0)2R†; wherein each R†is independently hydrogen, Ci-6aliphatic 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.

[0058] Suitable substituents on the aliphatic group of R†are independently halogen, -R', -(haloR*), -OH, -OR', -O(haloR'), -CN, -C(0)OH, -C(0)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, -0(CH2)o-iPh, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0059] 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, camphor sulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, 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.

[0060] Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium andsalts. 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.

[0061] Unless otherwise stated, structures depicted herein are also meant to include all isomeric (e.g., enantiomeric, diastereomeric, and geometric (or conformational)) forms of thestructure; 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 a13C- or14C-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.

[0062] 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 μΜ, less than about 1 μΜ, less than about 500 nM, less than about 100 nM, less than about 10 nM, or less than about 1 nM.

[0063] 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.

[0064] 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, or14C), 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.

[0065] 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.

[0066] 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- ERF, 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.

[0067] 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 United States Patents 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.

[0068] 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:

[0069] As described above, in certain embodiments, the present invention provides a compound of formula I:Ior a pharmaceutically acceptable salt thereof, wherein:X1a bivalent moiety selected from a covalent bond, -CH2- -C(O)-, -C(S)-,R is hydrogen, deuterium, halogen, -CN, OR, SR, -S(0)R, -S(0)2R, -NR2, or an optionally substituted Ci-4 aliphatic;each R2is independently hydrogen, -R6, halogen, -CN, -NO2, -OR, -SR, - R2, -S(0)2R, -S(0)2R2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;RingRing B is a fused ring selected from 6-membered aryl containing 0-2 nitrogen atoms, 5 to 7- membered partially saturated carbocyclyl, 5 to 7-membered partially saturated heterocyclyl with 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur, or 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur;R3is selected from hydrogen, halogen, -OR, -N(R)2, or -SR;each R4is independently hydrogen, -R6, halogen, -CN, -NO2, -OR, -SR, - R2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;R5is hydrogen, C1-4 aliphatic, or -CN;each R6is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -N(R)-, - S-, -OC(O)-, -C(0)0-, -C(O)-, -S(O)-, -S(0)2-, -N(R)S(0)2-, -S(0)2N(R)-, -N(R)C(0)-, --, -OC(0)N(R)-, -N(R)C(0)0-,, 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, and sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partiallyunsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and 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 nitrogen, oxygen, or sulfur;;TBM is a target binding moiety;m is 0, 1, 2, 3 or 4;each of n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, or an optionally substituted group selected from Ci-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are 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, and sulfur.

[0070] As described above, in certain embodiments, the present invention provides a compound of formula I':I'or a pharmaceutically acceptable salt thereof, wherein:X1is a bivalent moiety selected from a covalent bond, -CH2- -C(O)-, -C(S)-, orR1is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(0)R, -S(0)2R, -NR2, or an optionally substituted Ci-4 aliphatic;each R2is independently hydrogen, -R6, halogen, -CN, -N02, -OR, -SR, -NR2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0)NR2,-C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;Ring A is a bi- or tricy wherein Ring B is other than imidazo or benzo, ein Ring B is other than benzo, wherein Ring B is other than benzwherein Ring B is other than benzo,Ring B is a fused ring selected from 6-membered aryl containing 0-2 nitrogen atoms, 5 to 7- membered partially saturated carbocyclyl, 5 to 7-membered partially saturated heterocyclyl with 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur, or 5- membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur;R3is selected from hydrogen, halogen, -OR, -N(R)2, or -SR;each R4is independently hydrogen, -R6, halogen, -CN, -N02, -OR, -SR, - R2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;R5is hydrogen, Ci-4 aliphatic, or -CN;each R6is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -N(R)-, - S-, -OC(O)-, -C(0)0-, -C(O)-, -S(O)-, -S(0)2-, -N(R)S(0)2-, -S(0)2N(R)-, -N(R)C(0)-, -n nC(0)N(R)-, -O -, N(R)C(0)0-,, 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, and sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1 -2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and 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 nitrogen, oxygen, or sulfur;;TBM is a target binding moiety;m is 0, 1, 2, 3 or 4;each of n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, or an optionally substituted group selected from Ci-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are taken together with their intervening atoms to form a4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur.

[0071] In certain embodiments, the present invention provides a compound of formula I":Ior a pharmaceutically acceptable salt thereof, wherein:X1is a bivalent moiet selected from a covalent bond, -C(R)2- -C(O)-, -C(S)-, -P(0)(OR)-, -X2is a carbon atom or silicon atom;X3is a bivalent moiety selected from -C(R)2- -N(R)-, -CF2- -CHF-, -S-, or -0-;X4is a bivalent moiety selected from a covalent bond or -C(R)2-;— is a single bond or double bond;R1is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(0)R, -S(0)2R, - R2, -P(0)(OR)2, -P(0)( R2)OR, -P(0)( R2)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, an optionally substituted C 1-4 aliphatic, or:R1and X1or X4are 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 nitrogen, oxygen, or sulfur; each R2is independently hydrogen, deuterium, -R6, halogen, -CN, -N02, -OR, -SR, -N(R)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0)NR2, -C(0)N(R)OR, -OC(0)R, -OC(0)NR2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0)NR2, -N(R)S(0)2R, -N(R)S(0)2NR2, -P(0)(OR)2, -P(0)(NR2)OR, or -P(0)NR2;Ring A i - or tricyclic ring selected fromwhereinRing B is a fused ring selected from 6-membered aryl containing 0-3 nitrogen atoms, 5 to 7- membered partially saturated carbocyclyl, 5 to 7-membered partially saturated heterocyclyl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5 -membered heteroaryl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur;R3is selected from hydrogen, deuterium, halogen, -CN, -N02, -OR, - R2, -SR, -S(0)2R, -S(0)2R2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0) R(OR), -OC(0)R, -OC(0) R2, -OP(0)(OR)2, -OP(0)( R2)2, -OP(0)(OR) R2, -N(R)C(0)R,-N(R)C(0)OR, -N(R)C(0) R2, -N(R)S(0)2R, -N(R)S(0)2NR2, -N(R)P(0)(OR)2, -N(R)P(0)(OR) R2, -P(0)(OR)2, -P(0)( R2)OR, -P(0)( R2)2, -Si(OH)2R, -Si(OH)(R)2, or -Si(R)3;each R4is independently hydrogen, deuterium, -R6, halogen, -S(0)2R, -S(0)2R2;-S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -P(0)(OR)2, -P(0)( R2)OR, or -P(0)( R2)2;R5is hydrogen, deuterium, an optionally substituted C1-4 aliphatic, or -CN;each R6is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring 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;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -N(R)- , -Si(R)2- -Si(OH)(R)-, -Si(OH)2- -C(H)(CF3)-, -P(0)(OR)-, -P(0)(R)-, -P(0)( R2)- , -S-, -OC(O)-, -C(0)0- -C(O)-, -S(O)-, -S(0)2- -N(R)S(0)2- - -, --C(0)N(R)- -OC(0)N(R)-, -N(R)C(0)0-wherein:each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, an 8-10 membered bicyclic arylenyl, a 4-8 membered saturated or partially unsaturated carbocyclylenyl, a 6-1 1 membered saturated or partially unsaturated spiro carbocyclylenyl, a 5-12 membered bridged or unbridged bicyclic saturated or partially unsaturated carbocyclylenyl, a 4-10 membered saturated or partially unsaturated heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 6-1 1 membered saturated or partially unsaturated spiroheterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 5-12 membered bridged or unbridged bicyclic saturated or partially unsaturated heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 5-6 membered heteroaryl enyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, or an 8-10 membered bicyclic heteroaryl enyl having 1-5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur;TBM is a target binding moiety;m is 0, 1, 2, 3 or 4;each of n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, or an optionally substituted group selected from Ci-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are 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, and sulfur.

[0072] As described above, in certain embodiments, the present invention provides a compound of formula II-A:II-Aor a pharmaceutically acceptable salt thereof, wherein:X1is a bivalent moiety selected from a covalent bond, -CH2- -C(O)-, -C(S)-, oris hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(0)R, -S(0)2R, -NR2, or an optionally substituted C1-4aliphatic;Ringeach R2is independently hydrogen, -R4, halogen, -CN, -N02, -OR, -SR, -NR2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0)NR2, -C(0)N(R)OR, -OC(0)R, -OC(0)NR2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0)NR2, or -N(R)S(0)2R;Ring B is selected from a 6-membered aryl containing 0-2 nitrogen atoms or a 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R3is independently hydrogen, -R4, halogen, -CN, -N02, -OR, -SR, -NR2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0)NR2,-C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;each R4is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;R5is hydrogen, Ci-4 aliphatic, or -CN;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -N(R)-, - S-, -OC(O)-, -C(0)0-, -C(O)-, -S(O)-, -S(0)2-, -N( -, -S(0)2N(R -, -N(R)C(0)-, --, -OC(0)N(R)-, -N(R)C(0)0-,, 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, and sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1 -2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered heteroaryl enyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroaryl enyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;TBM is a target binding moiety;m is 0, 1, or 2;n is 0, 1, 2, 3, or 4;p is 0 or 1, wherein when p is 0, the bond connecting Ring A and Ring B is connected toeach of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, or an optionally substituted group selected from Ci-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are 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, and sulfur.

[0073] As described above, in certain embodiments, the present invention provides a compound of formula II'-A:II'-Aor a pharmaceutically acceptable salt thereof, wherein:a bivalent moiety selected from a covalent bond, -CH2- -C(O)-, -C(S)-,is hydrogen, deuterium, halogen, -CN, OR, SR, -S(0)R, -S(0)2R, -NR2, or an optionally substituted Ci-4 aliphatic;Ring - or bicyclic ring selected fromeach R2is independently hydrogen, -R4, halogen, -CN, -NO2, -OR, -SR, - R2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;Ring B is selected from a 6-membered aryl containing 0-2 nitrogen atoms or a 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R3is independently hydrogen, -R4, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0)NR2, -C(0)N(R)OR, -OC(0)R, -OC(0)NR2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0)NR2, or -N(R)S(0)2R;each R4is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatomsindependently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;R5is hydrogen, C1-4aliphatic, or -CN;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -N(R)-, - S-, -OC(O)-, -C(0)0-, -C(O)-, -S(O)-, -S(0)2-, -N( -, -S(0)2N(R -, -N(R)C(0)-, --, -OC(0)N(R)-, -N(R)C(0)0-,, 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, and sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1 -2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered heteroaryl enyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroaryl enyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;TBM is a target binding moiety;m is 0, 1, or 2;n is 0, 1, 2, 3, or 4;p is 0 or 1, wherein when p is 0, the bond connecting Ring A and Ring B is connected toeach of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, or an optionally substituted group selected from Ci-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are 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, and sulfur.

[0074] In certain embodiments, the present invention provides a compound of Formula II"-A:II"-Aor a pharmaceutically acceptable salt thereof, wherein:X1is ivalent moiety selected from a covalent bond, -C(R)2- -C(O)-, -C(S)-, -P(0)(OR)-, -X2is a carbon atom or silicon atom;X3is a bivalent moiety selected from -C(R)2- -N(R)-, -CF2- -CHF-, -S-, or -0-;X4is a bivalent moiety selected from a covalent bond or -C(R)2-;— is a single bond or double bond;R1is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(0)R, -S(0)2R, - R2, -P(0)(OR)2, -P(0)( R2)OR, -P(0)( R2)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, an optionally substituted Ci-4 aliphatic, or:R1and X1or X4are 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 nitrogen, oxygen, or sulfur;each R2is independently hydrogen, deuterium, -R4, halogen, -CN, -N02, -OR, -SR, -N(R)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, -S(0)2R, -S(0)2R2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, -N(R)S(0)2R, -N(R)S(0)2R2, -P(0)(OR)2, -P(0)( R2)OR, or -P(0)( R2)2;Ring B is selected from a 6-membered aryl containing 0-3 nitrogen atoms or a 5-membered heteroaryl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur;each R3is selected from hydrogen, deuterium, -R4, halogen, -CN, -NO2, -OR, -NR2, -SR, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0) R(OR), -OC(0)R, -OC(0) R2, -OP(0)(OR)2, -OP(0)( R2)2, -OP(0)(OR) R2, -N(R)C(0)R, -N(R)C(0)OR, -N(R)C(0) R2, -N(R)S(0)2R, -N(R)S(0)2NR2, -N(R)P(0)(OR)2, -N(R)P(0)(OR) R2, -P(0)(OR)2, -P(0)( R2)OR, -P(0)( R2)2, -Si(OH)2R, -Si(OH)(R)2, or -Si(R)3;each R4is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;R5is hydrogen, deuterium, an optionally substituted C1-4 aliphatic, or -CN;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -N(R)- , -Si(R)2- -Si(OH)(R)-, -Si(OH)2- -P(0)(OR)-, -P(0)(R)-, -P(0)(NR2)-, -S-, - OC(O)-, -C(0)0- -C(O)-, -S(O)-, -S(0)2- -N(R) - -S(0)2N(R)- -N(R)C(0)-, -each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, an 8-10 membered bicyclic arylenyl, a 3-8 membered saturated or partially unsaturated carbocyclylenyl, a 6-11 membered saturated or partially unsaturated spiro carbocyclylenyl, a 5-12 membered bridged or unbridged bicyclic saturated or partially unsaturated carbocyclylenyl, a 4-10 membered saturated or partially unsaturated heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 6-11 membered saturated or partially unsaturated spiroheterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 5-12 membered bridged or unbridged bicyclic saturated or partially unsaturated heterocyclylenyl having 1 -4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 5-6 membered heteroaryl enyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, or an 8-10 membered bicyclic heteroaryl enyl having 1-5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur;TBM is a target binding moiety;m is 0, 1, or 2;n is 0, 1, 2, 3, or 4;p is 0 or 1, wherein when p is 0, the bond connecting Ring A and Ring B is connected toeach of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, or an optionally substituted group selected from Ci-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are 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, and sulfur.

[0075] As described above, in certain embodiments, the present invention provides a compound of formula II-B:II-Bor a pharmaceutically acceptable salt thereof, wherein:X1is a bivalent moiety selected from a covalent bond, -CH2- R1is hydrogen, deuterium, halogen,-S(0)R, -S(0)2R, -NR2, or an optionally substituted C1-4 aliphatic;each R2is independently hydrogen, -R4, halogen, -CN, -NO2, -OR, -SR, - R2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;Ring B is selected from a 6-membered aryl containing 0-2 nitrogen atoms or a 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R3is independently hydrogen, -R4, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0)NR2, -C(0)N(R)OR, -OC(0)R, -OC(0)NR2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0)NR2, or -N(R)S(0)2R;each R4is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;R5is hydrogen, C1-4 aliphatic, or -CN;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -N(R)-, - S-, -OC(O)-, -C(0)0-, -C(O)-, -S(O)-, -S(0)2-, -N(R)S(0)2-, -S(0)2N(R)-, -N(R)C(0)-, --OC(0)N(R , -N(R)C(0)0-,, 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, and sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and 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 nitrogen, oxygen, or sulfur;TBM is a target binding moiety;m is 0, 1, or 2;n is 0, 1, 2, 3, or 4;p is 0 or 1;each of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, or an optionally substituted group selected from Ci aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur.

[0076] As described above, in certain embodiments, the present invention provides a compound of formula II'-II'-Barmaceutically acceptable salt thereof, wherein:a bivalent moiety selected from a covalent bond, -CH2- is hydrogen, deuterium, halogen,-S(0)R, -S(0)2R, -NR2, or an optionally substituted Ci-4 aliphatic;Ring A iseach R2is independently hydrogen, -R4, halogen, -CN, -NO2, -OR, -SR, - R2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;Ring B is selected from a 6-membered aryl containing 0-2 nitrogen atoms or a 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R3is independently hydrogen, -R4, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0)NR2, -C(0)N(R)OR, -OC(0)R, -OC(0)NR2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0)NR2, or -N(R)S(0)2R;each R4is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;R5is hydrogen, C1-4 aliphatic, or -CN;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -N(R)-, - S-, -OC(O)-, -C(0)0-, -C(O)-, -S(O)-, -S(0)2-, -N(R)S(0)2-, -S(0)2N(R)-, -N(R)C(0)-, --OC(0)N(R , -N(R)C(0)0-,, 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, and sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and 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 nitrogen, oxygen, or sulfur;TBM is a target binding moiety;m is 0, 1, or 2;n is 0, 1, 2, 3, or 4;p is 0 or 1;each of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, or an optionally substituted group selected from Ci aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur.In certain embodiments, the present invention provides a compound of Formula II"-B:or a pharmaceutically acceptable salt thereof, wherein:X1is a bivalent moiety selected from a covalent bond -C(R)2- -C(O)-, -C(S)-, -P(0)(OR)-, -P(0)(R)-, -P(0)( R2)-, -S(O)-, -S(0)2- orX2is a carbon atom or silicon atom;X3is a bivalent moiety selected from -C(R)2- -N(R)-, -CF2- -CHF-, -S-, or -0-;X4is a bivalent moiety selected from a covalent bond or -C(R)2-;— is a single bond or double bond;R1is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(0)R, -S(0)2R, - R2, -P(0)(OR)2, -P(0)( R2)OR, -P(0)( R2)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, an optionally substituted C1-4 aliphatic, or:R1and X1or X4are 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 nitrogen, oxygen, or sulfur;each R2is independently hydrogen, deuterium, -R6, halogen, -CN, -NO2, -OR, -SR, - R2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, -N(R)S(0)2R, -N(R)S(0)2R2, -P(0)(OR)2, -P(0)( R2)OR, or -P(0)( R2)2;Ring B is selected from a 6-membered aryl containing 0-3 nitrogen atoms or a 5-membered heteroaryl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur;each R3is selected from hydrogen, deuterium, -R4, halogen, -CN, -NO2, -OR, -NR2, -SR, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0)NR2, -C(0)NR(OR), -OC(0)R, -OC(0)NR2, -OP(0)(OR)2, -OP(0)(NR2)2, -OP(0)(OR)NR2, -N(R)C(0)R, -N(R)C(0)OR, -N(R)C(0)NR2, -N(R)S(0)2R, -N(R)S(0)2NR2, -N(R)P(0)(OR)2,-N(R)P(0)(OR) R2, -P(0)(OR)2, -P(0)( R2)OR, -P(0)( R2)2, -Si(OH)2R, -Si(OH)(R)2, or -Si(R)3;each R4is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;R5is hydrogen, deuterium, an optionally substituted Ci-4 aliphatic, or -CN;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -N(R)- , -Si(R)2- -Si(OH)(R)-, -Si(OH)2- -P(0)(OR)-, -P(0)(R)-, -P(0)( R2)-, -S-, - OC(O)-, -C(0)0- -C(O)-, -S(O)-, -S(0)2- -N(R) - -S(0)2N(R)- -N(R)C(0)-, -each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, an 8-10 membered bicyclic arylenyl, a 3-8 membered saturated or partially unsaturated carbocyclylenyl, a 6-11 membered saturated or partially unsaturated spiro carbocyclylenyl, a 5-12 membered bridged or unbridged bicyclic saturated or partially unsaturated carbocyclylenyl, a 4-10 membered saturated or partially unsaturated heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 6-11 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 5-12 membered bridged or unbridged bicyclic saturated or partially unsaturated heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 5-6 memberedheteroarylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, or an 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur;TBM is a target binding moiety;m is 0, 1, or 2;n is 0, 1, 2, 3, or 4;p is 0 or 1;each of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, deuterium, or an optionally substituted group selected from Ci- 6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are 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, and sulfur.

[0078] As defined above and described herein, X1is a bivalent moiety selected from a covalent bond -CH2- -C(R)2- -C(O)-, -C(S)-, -CH(R)-, -CH(CF3)-, -P(0)(OR)-, -P(0)(R)-, -

[0079] In some embodiments, X1is a covalent bond. In some embodiments, X1is -CH2- In some embodiments, X1is -C(R)2- In some embodiments, X1is -C(O)-. In some embodiments, X1is -C(S)-. In some embodiments, X1is -CH(R)-. In some embodiments, X1is -CH(CF3)-. In some embodiments, X1is -P(0)(OR)-. In some embodiments, X1is -P(0)(R)-. In some embodiments, X1is -P(0)( R2)-. In som mbodiments, X1is -S(O)-. In some embodiments, X1is -S(0)2- In some embodiments, X1i is

[0080] In some embodiments, X1is selected from those depicted in Table 1, below.

[0081] As defined above and described herein, X2is a carbon atom or silicon atom.

[0082] In some embodiments, X2is a carbon atom. In some embodiments, X2is a silicon atom.

[0083] In some embodiments, X2is selected from those depicted in Table 1, below.

[0084] As defined above and described herein, X3is a bivalent moiety selected from -CH2--C(R)2- -N(R)-, -CF2- -CHF-, -S-, -CH(R)-, or -0-.

[0085] In some embodiments, X3is -CH2- In some embodiments, X1is -C(R)2- In some embodiments, X3is -N(R)-. In some embodiments, X3is -CF2- In some embodiments, X3is - CHF-. In some embodiments, X3is -S-. In some embodiments, X3is -CH(R)-. In some embodiments, X3is -0-.

[0086] In some embodiments, X3is selected from those depicted in Table 1, below.

[0087] As defined above and described herein, X4is a bivalent moiety selected from a covalent bond, -CH2- or -C(R)2-.

[0088] In some embodiments, X4is a covalent bond. In some embodiments, X4is -CH2- In some embodiments, X4is -C(R)2-

[0089] In some embodiments, X4is selected from those depicted in Table 1, below.

[0090] As defined above and described herein, R1is hydrogen, deuterium, halogen, -CN, - OR, -SR, -S(0)R, -S(0)2R, - R2, -P(0)(OR)2, -P(0)( R2)OR, -P(0)( R2)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, an optionally substituted Ci-4 aliphatic, or R1and X1or X4are 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 nitrogen, oxygen, or sulfur.

[0091] In some embodiments, R1is hydrogen. In some embodiments, R1is deuterium. In some embodiments, R1is halogen. In some embodiments, R1is -CN. In some embodiments, R1is -OR. In some embodiments, R1is -SR. In some embodiments, R1is -S(0)R. In some embodiments, R1is -S(0)2R. In some embodiments, R1is -NR2. In some embodiments, R1is - P(0)(OR)2. In some embodiments, R1is -P(0)(NR2)OR. In some embodiments, R1is - P(0)(NR2)2. In some embodiments, R1is -Si(OH)2R.In some embodiments, R1is -Si(OH)(R)2. In some embodiments, R1is -Si(R)3. In some embodiments, R1is an optionally substituted Ci-4 aliphatic. In some embodiments, R1and X1orX4are 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 nitrogen, oxygen, or sulfur.

[0092] In some embodiments, R1is selected from those depicted in Table 1, below.

[0093] As defined above and described herein, each R2is independently hydrogen, deuterium, -R6, halogen, -CN, -N02, -OR, -SR, -N(R)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, -S(0)2R, - S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, - N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, -N(R)S(0)2R, -N(R)S(0)2R2, -P(0)(OR)2, - P(0)( R2)OR, or -P(0)( R2)2.

[0094] In some embodiments, R2is hydrogen. In some embodiments, R2is deuterium. In some embodiments, R2is -R6. In some embodiments, R2is halogen. In some embodiments, R2is -CN. In some embodiments, R2is -N02. In some embodiments, R2is -OR. In some embodiments, R2is -Si(OH)2R. In some embodiments, R2is -Si(OH)(R)2. In some embodiments, R2is -SR. In some embodiments, R2is -NR2. In some embodiments, R2is -Si(R)3. In some embodiments, R2is -S(0)2R. In some embodiments, R2is -S(0)2NR2. In some embodiments, R2is -S(0)R. In some embodiments, R2is -C(0)R. In some embodiments, R2is -C(0)OR. In some embodiments, R2is -C(0)NR2. In some embodiments, R2is -C(0)N(R)OR. In some embodiments, R2is -OC(0)R. In some embodiments, R2is -OC(0)NR2. In some embodiments, R2is -N(R)C(0)OR. In some embodiments, R2is -N(R)C(0)R. In some embodiments, R2is -N(R)C(0)NR2. In some embodiments, R2is -N(R)S(0)2R. In some embodiments, R2is -P(0)(OR)2. In some embodiments, R2is -P(0)(NR2)OR. In some embodiments, R2is -P(0)(NR2)2.

[0095] In some embodiments, R2is selected from those depicted in Table 1, below.

[0096] As defined above and described herein, Ring A is a bi- or tricyclic ring selected from80Ring A isembodiments, Ring A is me embodiments, Ring A is. In some embodiments, Ring A is some embodiments, Ring A is odiments, Ring A is NR°In some embodiments, Ring In some embodiments, Ring A is. In some embodiments, Ring A is ome embodiments, RinA is. In some embodiments, Ring A is In some embodiments,Ring A is. insome embodiments, Ring A is . In some embodiments, Ring A isIn some embodiments, Ring A isembodiments, Ring A is . In some embodiments, Ring A is. In some embodiments, Ring A isisiInn ssoommee eemmbbooddiimmeennttss,, RRiinngg AA iiss . In some embodiments,Ring A is. In some embodiments, Ring A isIn some embodiments, Ring A isIn some embodiments Rin A isIn some embodiments, Ring A isT Inn s soommee e emmbbooddii .mmeennttss R Rii.nngcr A A i i.ss . In some embodiments,In some embodiments, Ring A is In some embodiments, Ring A isIn some embodiments, Ring A is . In some embodiments,Ring A is. In some embodiments, Ring A is In someembodiments, Ring A isIn some embodiments, Ring A isembodiments, Ring A is embodiments, Ring A isembodiments, Ring A is ome embodiments, Ring ome embodiments, Ring A is . In some embodiments,

[0099] In some embodiments, Ring A is selected from those depicted in Table 1, below.

[0100] As defined above and described herein, Ring B is a fused ring selected from 6- membered aryl containing 0-3 nitrogen atoms, 5 to 7-membered partially saturated carbocyclyl, 5 to 7-membered partially saturated heterocyclyl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or 5-membered heteroaryl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur.

[0101] In some embodiments, Ring B is a 6-membered aryl containing 0-3 nitrogen atoms. In some embodiments, Ring B is a 5 to 7-membered partially saturated carbocyclyl. In some embodiments, Ring B is 5 to 7-membered partially saturated heterocyclyl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, Ring B is 5-membered heteroaryl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. ome embodiments, Ring B issome embodiments, Ring B is In some embodiments, RingB isIn some embodiments, Ring

[0103] In some embodiments, each Ring B isIn some embodiments, eachesome embodiments, Ring B issome embodiments, Ring B is In some embodiments, Ring BIn some embodiments, Ring B is . In some embodiments, Ring B is n some embodiments, Ring B is In some embodiments, Ring B isIn some embodiments, Ring B is In some embodiments, Ring B isIn some embodiments, Ring B issome embodiments, Ring B is. In some embodiments, Ring B is In some embodiments, Ring B is. In some embodiments, Ring B is

[0108] In some embodiments, Ring B is selected from those depicted in Table 1, below.

[0109] As defined above and described herein,— is a single or double bond.

[0110] In some embodiments,— is a single bond. In some embodiments,— is a double bond.

[0111] In some embodiments,— is selected from those depicted in Table 1, below.

[0112] As defined above and described herein, R3is hydrogen, deuterium, halogen, -CN, - N02, -OR, - R2, -SR, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0) R(OR), -OC(0)R, -OC(0) R2, -OP(0)(OR)2, -OP(0)( R2)2, -OP(0)(OR) R2, -N(R)C(0)R, -N(R)C(0)OR, -N(R)C(0) R2, -N(R)S(0)2R, -N(R)S(0)2NR2, -N(R)P(0)(OR)2, -N(R)P(0)(OR) R2, -P(0)(OR)2, -P(0)( R2)OR, -P(0)( R2)2, -Si(OH)2R, -Si(OH)(R)2, or -Si(R)3.

[0113] In some embodiments, R3is hydrogen. In some embodiments, R3is deuterium. In some embodiments, R3is halogen. In some embodiments, R3is -CN. In some embodiments, R3is -N02. In some embodiments, R3is -OR. In some embodiments, R3is -NR2. In some embodiments, R3is -SR. In some embodiments, R3is -S(0)2R. In some embodiments, R3is - S(0)2NR2. In some embodiments, R3is -S(0)R. In some embodiments, R3is -C(0)R. In some embodiments, R3is -C(0)OR. In some embodiments, R3is -C(0)NR2. In some embodiments, R3is -C(0)NR(OR). In some embodiments, R3is -OC(0)R. In some embodiments, R3is -OC(0)NR2. In some embodiments, R3is -OP(0)(OR)2. In some embodiments, R3is -OP(0)(NR2)2. In some embodiments, R3is -OP(0)(OR)NR2. In some embodiments, R3is -N(R)C(0)R. In some embodiments, R3is -N(R)C(0)OR. In some embodiments, R3is -N(R)C(0)NR2. In some embodiments, R3is -N(R)S(0)2R. In some embodiments, R3is -N(R)S(0)2NR2. In some embodiments, R3is -N(R)P(0)(OR)2. In some embodiments, R3is-N(R)P(0)(OR) R2. In some embodiments, R3is -P(0)(OR)2. In some embodiments, R3is -P(0)( R2)OR. In some embodiments, R3is -P(0)(NR2)2. In some embodiments, R3is -Si(OH)2R. In some embodiments, R3is -Si(OH)(R)2. In some embodiments, R3is -Si(R)3.

[0114] In some embodiments, R3is methyl. In some embodiments, R3is -OCH3. In some embodiments, R3is chloro.

[0115] In some embodiments, R3is selected from those depicted in Table 1, below.

[0116] As defined above and described herein, each R4is independently hydrogen, deuterium, -R6, halogen, -CN, -N02, -OR, -SR, - R2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, -N(R)S(0)2R, -P(0)(OR)2, -P(0)( R2)OR, or -P(0)( R2)2.

[0117] In some embodiments, R4is hydrogen. In some embodiments, R4is -R6. In some embodiments, R4is halogen. In some embodiments, R4is -CN. In some embodiments, R4is - N02. In some embodiments, R4is -OR. In some embodiments, R4is -SR. In some embodiments, R4is -NR2. In some embodiments, R4is -S(0)2R. In some embodiments, R4is -S(0)2NR2. In some embodiments, R4is -S(0)R. In some embodiments, R4is -C(0)R. In some embodiments, R4is -C(0)OR. In some embodiments, R4is -C(0)NR2. In some embodiments, R4is - C(0)N(R)OR. In some embodiments, R4is -OC(0)R. In some embodiments, R4is -OC(0)NR2. In some embodiments, R4is -N(R)C(0)OR. In some embodiments, R4is -N(R)C(0)R. In some embodiments, R4is -N(R)C(0)NR2. In some embodiments, R4is -N(R)S(0)2R. In some embodiments, R4is -P(0)(OR)2. In some embodiments, R4is -P(0)(NR2)OR. In some embodiments, R4is -P(0)(NR2)2.

[0118] In some embodiments, R4is methyl. In some embodiments, R4is ethyl. In some embodiments, R4is cyclopropyl.

[0119] In some embodiments, R4is selected from those depicted in Table 1, below.

[0120] As defined above and described herein, R5is hydrogen, deuterium, an optionally substitute C1-4aliphatic, or -CN.

[0121] In some embodiments, R5is hydrogen. In some embodiments, R5is deuterium. In some embodiments, R5is an optionally substituted C1-4aliphatic. In some embodiments, R5is - CN.

[0122] In some embodiments, R5is selected from those depicted in Table 1, below.

[0123] As defined above and described herein, each R6is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur.

[0124] In some embodiments, R6is an optionally substituted Ci-6 aliphatic. In some embodiments, R6is an optionally substituted phenyl. In some embodiments, R6is an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur. In some embodiments, R6is an optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur.

[0125] In some embodiments, R6is selected from those depicted in Table 1, below.

[0126] As defined above and described herein, L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy- -0-, -N(R)-, -Si(R)2- -Si(OH)(R)-, -Si(OH)2- -P(0)(OR)-, -P(0)(R)-, -P(0)( R2)-, -S-, -OC(O)-, -C(0)0- -C(O)-, -S(O)-, -S(0)2- - - --, -N(R)C(0)- €(0)N(R) OC(0)N(R)-, N(R)C(0)0-

[0127] In some embodiments, L is a covalent bond. In some embodiments, L is a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy- -0-, -N(R)-, -Si(R)2- -Si(OH)(R)-, -Si(OH)2- , -P(0)(OR)-, -P(0)(R)-, -P(0)( R2)-, -S-, -OC(O)-, -C(0)0- -C(O)-, -S(O)-, -S(0)2- -N(R)S(0)2- -S(0)2N(R)-, -N(R)C(0)-, -C(0)N(R)-, -OC(0)N(R)-, -N(R)C(0)0-,In some embodiments, L is In someIn some embodiments, L isembodiments, L is s

[0129] In some embodiments, L is In some embodiments, LIn some embodiments, L is some embodiments,some embodiments,In some embodiments, L isIn some embodiments, L isIn some embodiments, L is

[0130] In some embodiments, L is selected from those depicted in Table 1, below.

[0131] As defined above and described herein, each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, an 8-10 membered bicyclic arylenyl, a 3-8 membered saturated or partially unsaturated carbocyclylenyl, a 6-11 membered saturated or partially unsaturated spiro carbocyclylenyl, a 5-12 membered bridged or unbridged bicyclic saturated or partially unsaturated carbocyclylenyl, a 4-10 membered saturated or partially unsaturated heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 6-11 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 5-12 membered bridged or unbridged bicyclic saturated or partially unsaturated heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, or an 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur.

[0132] In some embodiments, -Cy- is an optionally substituted bivalent ring selected from phenylenyl. In some embodiments, -Cy- is an optionally substituted 8-10 membered bicyclic arylenyl. In some embodiments, -Cy- is an optionally substituted 3-8 membered saturated or partially unsaturated carbocyclylenyl. In some embodiments, -Cy- is an optionally substituted 6- 11 membered saturated or partially unsaturated spiro carbocyclylenyl. In some embodiments, - Cy- is an optionally substituted 5-12 membered bridged or unbridged bicyclic saturated or partially unsaturated carbocyclylenyl. In some embodiments, -Cy- is an optionally substituted 4- 10 membered saturated or partially unsaturated heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur. In some embodiments, -Cy- is an optionally substituted 6-11 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen,oxygen, silicon, phosphorus, or sulfur. In some embodiments, -Cy- is an optionally substituted 5-12 membered bridged or unbridged bicyclic saturated or partially unsaturated heterocyclylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur. In some embodiments, -Cy- is an optionally substituted 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, or an 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur.

[0133] In some embodiments, -Cy- is

[0134] In some embodiments, -Cy- is selected from those depicted in Table 1, below.

[0135] As defined above and described herein, TBM is a target binding moiety.

[0136] In some embodiments, TBM is a target binding moiety.

[0137] In some embodiments. TBM binds to a protein selected from those listed in paragraph

[0181] .

[0138] In some embodiments TBM is selected from one of the drugs listed in Table 2, whereinthe drug is attached toat any modifiable carbon, oxygen, sulfur or nitrogen atom.00139] In some embodiments, TBM is selected from one of the drugs listed in Table 2, whereinat any modifiable carbon, oxygen, sulfur or nitrogen atom

[0140] In some embodiments, TBM is selected from one of the dru s listed in Table 2, whereinthe drug is attached toat any modifiable carbon, oxygen, sulfur or nitrogen atom.

[0141] In some embodiments, TBM is selected from one of the drugs listed in Table 2, whereinthe drug is attached toat any modifiable carbon, oxygen, sulfur or nitrogen atom.

[0142] In some embodiments, TBM In some embodiments, TBMisIn some embodiments, TBM is . In some

[0143] In some embodiments, TBM is selected from those depicted in Table 1, below.

[0144] As defined above and described herein, m is 0, 1, 2, 3 or 4.

[0145] In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4.

[0146] In some embodiments, m is selected from those depicted in Table 1, below.

[0147] As defined above and described herein, each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0148] In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5.In some embodiments, n is 6. In some embodiments, n is 7. In some embodiments, n is 8. In some embodiments, n is 9. In some embodiments, n is 10.

[0149] In some embodiments, n is selected from those depicted in Table 1, below.

[0150] As defined above and described herein, each R is independently hydrogen, deuterium, or an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur, or two R groups on the same nitrogen are 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, and sulfur.

[0151] In some embodiments, R is hydrogen. In some embodiments, R is deuterium. In some embodiments, R is optionally substituted Ci-6aliphatic. In some embodiments, R is optionally substituted phenyl. In some embodiments, R is optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur. In some embodiments, R is optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur. In some embodiments, two R groups on the same nitrogen are 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, and sulfur.

[0152] In some embodiments, R is selected from those depicted in Table 1, below.

[0153] In some embodiments, the present invention provides a compound of formula II-A or II-B, wherein X1, R1, R5, R, -Cy- and TBM are recited as for formula I as above and herein, and Ring A, Ring B, R2, R3, R4, L, m, n, p, and q are recited as for formula II-A and II-B as below and herein.

[0154] As defined above and described herein, Ring A is a mono- or bicyclic ring selectedfrome embodiments, Ring A is . In some embodiments, Ring A is. In some embodiments, Ring A is In some embodiments, Ringembodiments, Ring A isIn some embodiments, Ring A is . In some embodiments, Ring A is. In some embodiments, Ring A isIn some embodiments, Ring A is e embodiments, Ring A is. In some embodiments, Ring A is . In some embodiments, Ringembodiments, Ring A is . In some embodiments, Ring A is O In some embodiments, Ring A isin some embodiments, Ring A is00156] In some embodiments, Ring A is. In some embodiments, Ring A is ome embodiments, Ring. In some embodiments, Ring A is . In some embodiments,Ring A is. In some embodiments, Ring A is In some embodiments, Ring A is. In some embodiments, Ring A is . In some embodiments, Ring A is. In some embodiments, Ring A isIn some embodiments, Ring A isin some embodiments, Ring A is. In some embodiments, Ring A is . In some embodiments,embodiment, Ring A is .- or bicyclic ring selected from

[0158] In some embodiments, Ring A is a mono- or bicyclic ring selected from102103104

[0161] In some embodiments, Ring A is selected from those depicted in Table 1, below.

[0162] As defined above and described herein, each R2is independently hydrogen, deuterium, -R4, halogen, -CN, -N02, -OR, -SR, - R2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, -N(R)S(0)2R, -N(R)S(0)2R2, -P(0)(OR)2, -P(0)( R2)OR, or -P(0)( R2)2.

[0163] In some embodiments, R2is hydrogen. In some embodiments, R2is deuterium. In some embodiments, R2is -R4. In some embodiments, R2is halogen. In some embodiments, R2is -CN. In some embodiments, R2is -N02. In some embodiments, R2is -OR. In some embodiments, R2is -Si(OH)2R. In some embodiments, R2is -Si(OH)(R)2. In some embodiments, R2is -SR. In some embodiments, R2is -NR2. In some embodiments, R2is -Si(R)3. In some embodiments, R2is -S(0)2R. In some embodiments, R2is -S(0)2NR2. In some embodiments, R2is -S(0)R. In some embodiments, R2is -C(0)R. In some embodiments, R2is -C(0)OR. In some embodiments, R2is -C(0)NR2. In some embodiments, R2is -C(0)N(R)OR. In some embodiments, R2is -OC(0)R. In some embodiments, R2is -OC(0)NR2. In some embodiments, R2is -N(R)C(0)OR. In some embodiments, R2is -N(R)C(0)R. In some embodiments, R2is -N(R)C(0)NR2. In some embodiments, R2is -N(R)S(0)2R. In someembodiments, R2is -P(0)(OR)2. In some embodiments, R2is -P(0)( R2)OR. In some embodiments, R2is -P(0)( R2)2.

[0164] In some embodiments, R2is methyl.

[0165] In some embodiments, R2is selected from those depicted in Table 1, below.

[0166] As defined above and described herein, Ring B is selected from a 6-membered aryl containing 0-3 nitrogen atoms or a 5-membered heteroaryl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur.

[0167] In some embodiments, Ring B is a 6-membered aryl containing 0-3 nitrogen atoms. In some embodiments, Ring B is a 5-membered heteroaryl with 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur.

[0168] In some embodiments, Ring B is selected from those depicted in Table 1, below.

[0169] As defined above and described herein, each R3is independently hydrogen, deuterium, halogen, -CN, -N02, -OR, - R2, -SR, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, - C(0) R2, -C(0) R(OR), -OC(0)R, -OC(0) R2, -OP(0)(OR)2, -OP(0)( R2)2, -OP(0)(OR) R2, -N(R)C(0)R, -N(R)C(0)OR, -N(R)C(0) R2, -N(R)S(0)2R, -N(R)S(0)2NR2, -N(R)P(0)(OR)2, -N(R)P(0)(OR) R2, -P(0)(OR)2, -P(0)( R2)OR, -P(0)( R2)2, -Si(OH)2R, -Si(OH)(R)2, or -Si(R)3.

[0170] In some embodiments, R3is hydrogen. In some embodiments, R3is deuterium. In some embodiments, R3is halogen. In some embodiments, R3is -CN. In some embodiments, R3is -N02. In some embodiments, R3is -OR. In some embodiments, R3is -NR2. In some embodiments, R3is -SR. In some embodiments, R3is -S(0)2R. In some embodiments, R3is - S(0)2NR2. In some embodiments, R3is -S(0)R. In some embodiments, R3is -C(0)R. In some embodiments, R3is -C(0)OR. In some embodiments, R3is -C(0)NR2. In some embodiments, R3is -C(0)NR(OR). In some embodiments, R3is -OC(0)R. In some embodiments, R3is -OC(0)NR2. In some embodiments, R3is -OP(0)(OR)2. In some embodiments, R3is -OP(0)(NR2)2. In some embodiments, R3is -OP(0)(OR)NR2. In some embodiments, R3is -N(R)C(0)R. In some embodiments, R3is -N(R)C(0)OR. In some embodiments, R3is -N(R)C(0)NR2. In some embodiments, R3is -N(R)S(0)2R. In some embodiments, R3is -N(R)S(0)2NR2. In some embodiments, R3is -N(R)P(0)(OR)2. In some embodiments, R3is -N(R)P(0)(OR)NR2. In some embodiments, R3is -P(0)(OR)2. In some embodiments, R3is-P(0)( R2)OR. In some embodiments, R3is -P(0)(NR2)2. In some embodiments, R3is - Si(OH)2R. In some embodiments, R3is -Si(OH)(R)2. In some embodiments, R3is -Si(R)3.

[0171] In some embodiments, R3is selected from those depicted in Table 1, below.

[0172] As defined above and described herein, each R4is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur.

[0173] In some embodiments, R4is an optionally substituted Ci-6 aliphatic. In some embodiments, R4is an optionally substituted phenyl. In some embodiments, R4is an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur. In some embodiments, R4is an optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur.

[0174] In some embodiments, R4is methyl.

[0175] In some embodiments, R4is selected from those depicted in Table 1, below.

[0176] As defined above and described herein, L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy- -0-, -N(R)-, -Si(R)2- -Si(OH)(R)-, -Si(OH)2- -P(0)(OR)-, -P(0)(R)-, -P(0)( R2)-, -S-, -OC(O)-, -C(0)0- -C(O)-, -S(O)-, -S(0)2- -N(R)S(0)2- -S(0)2N(R)-, -N(R)C(0)-, -C(0 -, -OC(0)N(R)-, -N(R)C(0)0-

[0177] In some embodiments, L is a covalent bond. In some embodiments, L is a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy- -0-, -N(R)-, -Si(R)2- -Si(OH)(R)-, -Si(OH)2-, -P(0)(OR)-, -P(0)(R)-, -P(0)( R2)-, -S- C(0)0- -C(O)-, -S(O)-, -S(0)2- - N(R)S(0)2- -S(0)2N(R)-, -N -:OC(0)N(R)-, N(R)C(0)0-

[0178] In some embodiments, L is selected from those depicted in Table 1, below.

[0179] As defined above and described herein, m is 0, 1, or 2.

[0180] In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2.

[0181] In some embodiments, m is selected from those depicted in Table 1, below.

[0182] As defined above and described herein, n is 0, 1, 2, 3, or 4.

[0183] In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4.

[0184] In some embodiments, n is selected from those depicted in Table 1, below.

[0185] As defined above and described h wherein when p is 0, the bondconnecting Ring A and Ring B is connected to

[0186] In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, pis 0 and the bond connecting Ring A and Ring B is connected to

[0187] In some embodiments, p is selected from those depicted in Table 1, below.

[0188] As defined above and described herein, each of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0189] In some embodiments, q is 0. In some embodiments, q is 1. In some embodiments, q is 2. In some embodiments, q is 3. In some embodiments, q is 4. In some embodiments, q is 5. In some embodiments, q is 6. In some embodiments, q is 7. In some embodiments, q is 8. In some embodiments, q is 9. In some embodiments, q is 10.

[0190] In some embodiments, q is selected from those depicted in Table 1, below.

[0191] 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.

[0192] 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.

[0193] 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, membranefusion, 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.

[0194] TBM (or target binding moiety) is a small molecule which is capable of binding to or binds to a target protein of interest.

[0195] 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).

[0196] In some embodiments, TBM is a BRD ligand selected from111112113114115116117

[0200] In some embodiments, TBM is a glucocorticoid receptor ligand selected from119120121wherein R denotes attachment to

[0205] In some embodiments, TBM is a RasG12C ligand selected fromand selected from00207] In some embodiments, TBM is a Bcl-2 / Bcl-XL ligand selected from131ı32ı33nitrogen or sulfur atom.

[0211] In some embodiments, TBM is an Abl, KRAS, SHP2, cRAF, MerTK or PRMT5 ligand that are selected from the following non-limiting examples:AblKRASSHP2cRAFMerTKis attached to a modifiable carbon, oxygen, nitrogen or sulfur atom.

[0212] In some embodiments, a TBM moiety is selected from PTM moieties as recited in WO 2016 / 197032 the entirety of which is incorporated herein by reference. In some embodiments, a TBM moiety is selected from such inhibitors as described in WO 2016 / 197032 at paragraphs

[0116] through

[0173] wherein the recitation of a "Linker" moiety in WO 2016 / 197032 corresponds to the -L- group as defined and described herein.whereinis attached to a modifiable carbon, nitrogen or sulfur atom.

[0214] Exemplary compounds of the invention are set forth in Table 1, below. Table 1. Exemplary CompoundsCompoundStructureNumber

[0215] In some embodiments, the method employs a compound set forth in Table 1, above, or a pharmaceutically acceptable salt thereof.

[0216] In some embodiments, the present invention provides a compound of formula I, wherein the compound is not any of compounds depicted in Table A-1, below.Table A-l.

[0218] In some embodiments, the present invention provides a compound of formula II-A, wherein the compound is not any of compounds depicted in Table A-2, below.

[0219] Table A-2nitrogen or sulfur atom.

[0221] Table 2. Exemplary Drugs with Disease Indications and Gene Identifier for the Target ProteinDrug Name Indication(s) Gene7a-methyl-19- hormone replacement,male AR nortestosterone,MENT contraceptiveA-007 antineoplastic agent ESR1A-007 antineoplastic agent ESR2 oxybutynin for treatment of incontinence CHRM1 oxybutynin for treatment of incontinence CHRM2 oxybutynin for treatment of incontinence CHRM3Testosterone hormone replacement ARABC294640 antineoplastic agent SPHK1ABC294640 antineoplastic agent SPHK2Aripiprazole antipsychotic agent DRD2Aripiprazole antipsychotic agent HTR1AAripiprazole antipsychotic agent HTR2A paclitaxel antineoplastic agent BCL2 paclitaxel antineoplastic agent TUBB1 navitoclax, ABT-263 antineoplastic agent BCL2 navitoclax, ABT-263 antineoplastic agent BCL2L1 navitoclax, ABT-263 antineoplastic agent BCL2L2 fenofibrate antidyslipidaemic agent PPARALinifanib antineoplastic agent CSF1RLinifanib antineoplastic agent FLT1Linifanib antineoplastic agent FLT3Linifanib antineoplastic agent FLT4Linifanib antineoplastic agent KDRLinifanib antineoplastic agent KITLinifanib antineoplastic agent PDGFRBLinifanib antineoplastic agent RETLinifanib antineoplastic agent TIE2Drug Name Indication(s) GeneAC-201 antidiabetic IL1BAC-201 antidiabetic IL1RN quizartinib antineoplastic agent FLT3AC430 antiinflammatory JAK2 agent,antineoplastic agentAC480 antineoplastic agent EGFRAC480 antineoplastic agent ERBB2AC480 antineoplastic agent ERBB3AC480 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 NO S3Acccretropin 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 acoti amide for treatment of functional dyspepsia ACHEACP-001 hormone replacement GHRACP-104 antipsychotic agent CHRM1ACP-104 antipsychotic agent DRD2Drug Name Indication(s) GeneACP-104 antipsychotic agent DRD3ACP-104 antipsychotic agent HTR2AACTB1003 antineoplastic agent FGFR1ACTB1003 antineoplastic agent FGFR2ACTB1003 antineoplastic agent FGFR3ACTB1003 antineoplastic agent FGFR4ACTB1003 antineoplastic agent RPS6KB1ACY-1215 antineoplastic agent HDAC6AD 337 analgesic,for treatment of SLC6A2 fibromyalgiaAD 337 analgesic,for treatment of SLC6A4 fibromyalgiafentanyl analgesic OPRD1 fentanyl analgesic OPRM1 theophylline bronchodilator AD OR A 1 theophylline bronchodilator ADORA2A theophylline bronchodilator ADORA2B theophylline bronchodilator PDE3A theophylline bronchodilator PDE4A theophylline bronchodilator PDE4B theophylline bronchodilator PDE5AADL5747 analgesic OPRD1ADL5859 analgesic OPRD1ADL5945 motilitant OPRM1ADL7445 motilitant OPRM1 capsaicin analgesic TRPV1 fluticasone propionate bronchodilator R3C1 salmeterol bronchodilator ADRB2Drug Name Indication(s) GeneADX10059 antimigraine agent,for treatment of GRM5 gastroesophageal reflux diseaseADX415 antihypertensive agent ADRA2AADX-71149 antipsychotic GRM2 agent, anti depres sant, anxi olyti cfentanyl analgesic OPRD1 fentanyl analgesic OPRM1AES-103 for treatment of sickle-cell disease HBB doxorubicin antineoplastic agent TOP2AAEZS-112, ZEN-012 antineoplastic agent TOP2AAEZS-112, ZEN-012 antineoplastic agent TUBBAEZS-112, ZEN-012 antineoplastic agent TUBB1Afamelanotide 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 CHRNA2AGI-1067, succinobucol antiatherosclerosis agent VCAM1AGIX-4207 antiinflammatory agent,DMARD unknownAGN-214868 analgesic,neuralgia ADRA1AAGN-214868 analgesic,neuralgia ADRA1BAGN-214868 analgesic,neuralgia ADRA1DAGN-214868 analgesic,neuralgia ADRA2AAGN-214868 analgesic,neuralgia ADRA2BAGN-214868 analgesic,neuralgia ADRA2CDrug Name Indication(s) Gene agomelatine antidepressant MTNR1B agomelatine antidepressant HTR2B agomelatine antidepressant HTR2C agomelatine antidepressant MTNR1A hydroxychloroquine antirheumatic agent TLR7 hydroxychloroquine antirheumatic agent TLR9 paclitaxel antineoplastic agent BCL2 paclitaxel antineoplastic agent TUBB1AIKO-150 opioid antagonist OPRM1AIR645 antiasthmatic agent IL4RAAKB-6548 for treatment of anaemia EGLN1AKB-6548 for treatment of anaemia EGLN2AKL-0707 hormone replacement GHRHALB 109564(a) antineoplastic agent TUBBALB-127158(a) antiobesity agent MCHR1 salbutamol bronchodilator ADRB2 aleglitazar cardiovascular agent PPARA aleglitazar cardiovascular agent PPARG alfuzosin for treatment of benign prostatic ADRA1A hyperplasiaalfuzosin for treatment of benign prostatic ADRA1B hyperplasiaalfuzosin for treatment of benign prostatic ADRA1D hyperplasialidocaine anesthetic SCN10A lidocaine anesthetic SCN5A lidocaine anesthetic SCN9A pemetrexed antineoplastic agent DHFRDrug Name Indication(s) Gene 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 CACNA1 S amlodipine antihypertensive agent CACNA2D1 amlodipine antihypertensive agent CACNB2Alitretionine antineoplastic agent RARAAlitretionine antineoplastic agent RARBAlitretionine antineoplastic agent RARGAlitretionine antineoplastic agent RXRAAlitretionine antineoplastic agent RXRBAlitretionine antineoplastic agent RXRGAlitretionine antineoplastic agent RARAAlitretionine antineoplastic agent RARBAlitretionine antineoplastic agent RARGAlitretionine antineoplastic agent RXRAAlitretionine antineoplastic agent RXRBAlitretionine antineoplastic agent RXRGALKS 33 for treatment of alcohol OPRD1 dependance,antidepressantALKS 33 for treatment of alcohol OPRK1 dependance,antidepressantALKS 33 for treatment of alcohol OPRM1 dependance,antidepressantbaclofen for treatment of alcohol dependance GABBRlDrug Name Indication(s) Gene baclofen for treatment of alcohol dependance GABBR2ALKS 33 for treatment of alcohol OPRD1 dependance,antidepressantALKS 33 for treatment of alcohol OPRK1 dependance,antidepressantALKS 33 for treatment of alcohol OPRM1 dependance,antidepressantALKS 37 motilitant OPRD1ALKS 37 motilitant OPRK1ALKS 37 motilitant OPRM1ALKS 33 for treatment of alcohol OPRD1 dependance,antidepressantALKS 33 for treatment of alcohol OPRK1 dependance,antidepressantALKS 33 for treatment of alcohol OPRM1 dependance,antidepressantbuprenorphine antidepressant, analgesic,for OPRD1 treatment of opioid addictionbuprenorphine antidepressant, analgesic,for OPRK1 treatment of opioid addictionalmorexant 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 OPRK1Drug Name Indication(s) Gene 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 syndromealprazolam 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 GABRQDrug Name Indication(s) Gene alprazolam anxiolytic, sedative,hypnotic GABRR2 alprazolam anxiolytic, sedative,hypnotic GABRR3 alprostadil for treatment of erectile PTGER1 dysfunction, for treatment of sexualdysfunction in womenalprostadil for treatment of erectile PTGER2 dysfunction, for treatment of sexualdysfunction in womenalprostadil for treatment of erectile PTGER1 dysfunction, for treatment of sexualdysfunction in womenalprostadil for treatment of erectile PTGER2 dysfunction, for treatment of sexualdysfunction in womenalprostadil for treatment of erectile PTGER1 dysfunction, for treatment of sexualdysfunction in womenalprostadil for treatment of erectile PTGER2 dysfunction, for treatment of sexualdysfunction in womenaltropane diagnostic agent for parkinson's SLC6A3 disease and ADHDAlvespimycin antineoplastic agent HSP90AA1Alvespimycin antineoplastic agent HSP90AB1AM-101 for treatment of tinnitus GRIN1AM-101 for treatment of tinnitus GRIN2AAM-101 for treatment of tinnitus GRIN2BAM-101 for treatment of tinnitus GRIN2CDrug Name Indication(s) GeneAM-101 for treatment of tinnitus GRIN2DAM-101 for treatment of tinnitus GRIN3AAM-101 for treatment of tinnitus GRIN3BAM- 103 antiinflammatory agent ALOX5APAM- 152 antiinflammatory agent,antifibrotic LPAR1 agentAM-211 antiinflammatory agent,antiallergy GPR44 agentAM-461 antiinflammatory agent PTGDRAM-803 antiinflammatory agent ALOX5APAMAP102 antiinflammatory agent,DMARD HTR2BAMAP102 antiinflammatory agent,DMARD HTR2CAMD-070 antiviral agent,HIV CXCR4ALS 2-0426 antidiabetic DPP4 amibegron antidepressant ADRB3 amifostine radiation-protective agent ALPPL2 amiodarone antiarrhytmic agent ADRA1A amiodarone antiarrhytmic agent ADRB1 amiodarone antiarrhytmic agent KC H2 amisulpride antipsychotic agent DRD2 amisulpride antipsychotic agent DRD3 amitriptyline analgesic SLC6A2 amitriptyline analgesic SLC6A4 ketamine analgesic GRIN3A amlodipine antihypertensive agent, CACNA1C cardiovascular agentamlodipine antihypertensive agent, CACNA1D cardiovascular agentDrug Name Indication(s) Gene amlodipine antihypertensive agent, CACNA1 S cardiovascular agentamlodipine antihypertensive agent, CACNA2D1 cardiovascular agentamlodipine antihypertensive agent, CACNB2 cardiovascular agentamonafide antineoplastic agent TOP2A amonafide antineoplastic agent TOP2B aliskiren antihypertensive agent REN amlodipine antihypertensive agent CACNA1C amlodipine antihypertensive agent CACNA1D amlodipine antihypertensive agent CACNA1 S amlodipine antihypertensive agent CACNA2D1 amlodipine antihypertensive agent CACNB2 hy drochl orothi azi de antihypertensive agent SLC12A3AN-2728 antiinflammatory agent, antipsoriatic PDE4AAN-2728 antiinflammatory agent, antipsoriatic PDE4BAN-2898 antiinflammatory agent, antipsoriatic PDE4AAN-2898 antiinflammatory agent, antipsoriatic PDE4BANA773 antineoplastic agent TLR7Anacetrapib for treatment of dyslipidemia CETP anamorelin appetite stimulating agent GHSR anastrozole antineoplastic agent CYP19A1 anatibant for treatment of traumatic brain BDKRB2 injuryANA VEX 2-73 for treatment of Alzheimer's disease SIGMAR1 clomifene for treatment of testosterone ESR1deficiencyDrug Name Indication(s) Gene anhydrovinblastin antineoplastic agent TUBB docetaxel antineoplastic agent TUBB1AP1030 antiobesity agent MC1RAP1030 antiobesity agent MC4R oxybutynin for treatment of overactive bladder CHRM1 oxybutynin for treatment of overactive bladder CHRM2 oxybutynin for treatment of overactive bladder CHRM3APC-100 antineoplastic agent ARAPD125 for treatment of insomnia HTR2AAPD421 antiemetic DRD2APD668 antidiabetic GPR119APD791 antithrombotic HTR2AAPD916 for treatment of narcolepsy HRH3 mepivacaine anestethic SCN10A granisetron antiemetic HTR3A apilimod antiinflammatory agent, antipsoriatic unknown apixaban antithrombotic F10 misoprostol labor-inducing agent PTGIRAplindore antiparkinson agent,for treatment of DRD2 restlegs legs syndromeapomorphine for treatment of sexual dysfunction in DRD2 women,for treatment of erectile dysfunction,antiparkinson agentapomorphine for treatment of sexual dysfunction in DRD3 women,for treatment of erectile dysfunction,antiparkinson agentDrug Name Indication(s) Gene apomorphine for treatment of sexual dysfunction in DRD4 women,for treatment of erectile dysfunction,antiparkinson agentapomorphine for treatment of sexual dysfunction in DRD2 women,for treatment of erectile dysfunction,antiparkinson agentapomorphine for treatment of sexual dysfunction in DRD3 women,for treatment of erectile dysfunction,antiparkinson agentapomorphine for treatment of sexual dysfunction in DRD4 women,for treatment of erectile dysfunction,antiparkinson agentapremilast antiinflammatory agent, DMARD, PDE4A antipsoriaticapremilast antiinflammatory agent, DMARD, PDE4B antipsoriaticaprepitant antiemetic TACR1 apricoxib antineoplastic agent PTGS2AR-12 antineoplastic agent PDK1AR-12286 for treatment of glaucoma ROCK1AR-12286 for treatment of glaucoma ROCK2AR-42 antineoplastic agent HDAC1AR-42 antineoplastic agent HDAC10AR-42 antineoplastic agent HDAC11AR-42 antineoplastic agent HDAC2AR-42 antineoplastic agent HDAC3AR-42 antineoplastic agent HDAC4AR-42 antineoplastic agent HDAC5Drug Name Indication(s) GeneAR-42 antineoplastic agent HDAC6AR-42 antineoplastic agent HDAC7AAR-42 antineoplastic agent HDAC8AR-42 antineoplastic agent HDAC9AR9281 antihypertensive agent EPHX1AR9281 antihypertensive agent EPHX2 arbaclofen symptomatic treatment for fragile X GABBR1 syndromearbaclofen symptomatic treatment for fragile X GABBR2 syndromeARC 100 antineoplastic agent TUBB1 clonidine for treatment of diabetic ADRA2A neuropathy,for treatment ofADHD,antimucositicclonidine for treatment of diabetic ADRA2B neuropathy,for treatment ofADHD,antimucositicclonidine for treatment of diabetic ADRA2C neuropathy,for treatment ofADHD,antimucositicARD-07 for treatment of growth hormone GHR deficiencyArgatroban anticoagulant F2ARI-2243 antidiabetic DPP4ARI-3037MO Vitamin B analog,for treatment for GPR109A hyperlipidemiaARI-3037MO Vitamin B analog,for treatment for GPR109B hyperlipidemiaDrug Name Indication(s) GeneARI-3037MO Vitamin B analog,for treatment for NNMT hyperlipidemiaARI-3037MO Vitamin B analog,for treatment for QPRT hyperlipidemiaarmodafinil central nervous system stimulant SLC6A3ARN-509 antineoplastic agent ARARQ-197 antineoplastic agent METARQ-501 antineoplastic agent TOPIARQ-621 antineoplastic agent KIF11ARRY-162 antiinflammatory MAP2K1 agent,DMARD,antineoplastic agentARRY-162 antiinflammatory MAP2K2 agent,DMARD,antineoplastic agentARRY-300 antiinflammatory MAP2K1 agent,DMARD,antineoplastic agentARRY-300 antiinflammatory MAP2K2 agent,DMARD,antineoplastic agentARRY-334543 antineoplastic agent EGFRARRY-334543 antineoplastic agent ERBB2ARRY-380 antineoplastic agent ERBB2ARRY-403 antidiabetic GCKARRY-614 for treatment of myelodysplastic ABLl syndromeARRY-614 for treatment of myelodysplastic KDR syndromeARRY-614 for treatment of myelodysplastic MAPK11 syndromeDrug Name Indication(s) GeneARRY-614 for treatment of myelodysplastic MAPK12 syndromeARRY-614 for treatment of myelodysplastic MAPK13 syndromeARRY-614 for treatment of myelodysplastic MAPK14 syndromeARRY-614 for treatment of myelodysplastic TEKsyndromeARRY-797 antineoplastic agent MAPK11ARRY-797 antineoplastic agent MAPK12ARRY-797 antineoplastic agent MAPK13ARRY-797 antineoplastic agent MAPK14 arsenic trioxide antineoplastic agent CC D1 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 syndromearverapamil for treatment of irritable bowel CACNA1D syndromearverapamil for treatment of irritable bowel CACNA1F syndromearverapamil for treatment of irritable bowel CACNA1G syndromearverapamil for treatment of irritable bowel CACNA1 S syndromeDrug Name Indication(s) Gene arverapamil for treatment of irritable bowel CAC B1 syndromearverapamil for treatment of irritable bowel CAC B2 syndromearverapamil for treatment of irritable bowel CAC B3 syndromearverapamil for treatment of irritable bowel CAC B4 syndromesufentanil 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 GABRR1Drug Name Indication(s) Gene triazolam analgesic,sedative GABRR2 triazolam analgesic,sedative GABRR3Arzoxifene antineoplastic agent, antiosteoporotic ESR1 agentASC-J9 dermatological agent ARAsenapine antipsychotic agent ADRA 1 AAsenapine antipsychotic agent ADRA2AAsenapine antipsychotic agent ADRA2BAsenapine antipsychotic agent ADRA2CAsenapine antipsychotic agent DRD1Asenapine antipsychotic agent DRD2Asenapine antipsychotic agent DRD3Asenapine antipsychotic agent DRD4Asenapine antipsychotic agent HRH1Asenapine antipsychotic agent HRH2Asenapine antipsychotic agent HTR1AAsenapine antipsychotic agent HTR1BAsenapine antipsychotic agent HTR2AAsenapine antipsychotic agent HTR2BAsenapine antipsychotic agent HTR2CAsenapine antipsychotic agent HTR5AAsenapine antipsychotic agent HTR6Asenapine antipsychotic agent HTR7 asimadoline analgesic OPRK1 ipragliflozin antidiabetic SLC5A2AT-101 antineoplastic agent BADAT-101 antineoplastic agent BCL2AT-101 antineoplastic agent MCL1Drug Name Indication(s) GeneAT13387 antineoplastic agent HSP90AA1AT13387 antineoplastic agent HSP90AB1 fentanyl analgesic OPRD1 fentanyl analgesic OPRD1 fentanyl analgesic OPRM1 fentanyl analgesic,opioid OPRM1AT7519 antineoplastic agent CDK2AT9283 antineoplastic agent AURKAAT9283 antineoplastic agent AURKB atamestane antineoplastic agent CYP19A1 toremifene antineoplastic agent ESR1 toremifene antineoplastic agent ESR2ATHX-105 antiobesity agent HTR2C docetaxel antineoplastic agent TUBB1ATI-7505 Parasympathomimetic HTR4 prednisone antiinflammatory R3C1 agent, corti costeroi datomoxetine for treatment of ADHD SLC6A2 atorvastatin antihypecholesterolemic agent HMGCR atrasentan antineoplastic agent ED RAAUS-131 for treatment of menopausal ESR2symtpomsAV-412 antineoplastic agent EGFRAV-412 antineoplastic agent ERBB2AV608 antidepressant,for treatment of TACR1 irritable bowelsyndrome,antispasmodictivozanib antineoplastic agent FLT1Drug Name Indication(s) Gene tivozanib antineoplastic agent FLT4 tivozanib antineoplastic agent KDRAvanafil for treatment of erectile dysfunction PDE5AAVE- 1625 antiobesity agent,for treatment for C R1Alzheimer's diseasephentolamine for treatment of erectile dysfunction ADRA1A phentolamine for treatment of erectile dysfunction ADRA2AAVL-292 antineoplastic agent BTKAVN-101 for treatment of alzheimer's disease HTR6AVN-211 antipsychotic agent HTR6AVN-322 for treatment of alzheimer's disease HTR6AVN-944 antineoplastic agent IMPDH1AVN-944 antineoplastic agent IMPDH2 avosentan antihypertensive agent ED RA dextromethorphan antitussive agent GRIN3A dextromethorphan antitussive agent SIGMARl axitinib antineoplastic agent FLT1 axitinib antineoplastic agent FLT4 axitinib antineoplastic agent KDR axitinib antineoplastic agent KIT axitinib antineoplastic agent PDGFRA axitinib antineoplastic agent PDGFRBAXL1717 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 GABRA4Drug Name Indication(s) Gene 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 DNMT1AZD-0837 anticoagulant F2AZD2066 analgesic,for treatment of GRM5 gastroesophageal reflux diseaseAZD6244, ARRY-142886 antineoplastic agent MAP2K1AZD6244, ARRY-142886 antineoplastic agent MAP2K2AZD-8330 antineoplastic agent MAP2K1Drug Name Indication(s) GeneAZD-8848 antiallergy agent TLR7 azelastine antiallergy agent HRH1 azelastine antiallergy agent HRH1 azil sartan antihypertensive agent AGTR1 balsalazide antiinflammatory agent ALOX5 balsalazide antiinflammatory agent PPARG balsalazide antiinflammatory agent PTGS1 balsalazide antiinflammatory agent PTGS2 bardoxolone antineoplastic agent FKB1 bazedoxifene antiosteoporotic agent ESR1 bazedoxifene antiosteoporotic agent ESR2 ulodesine antiinflammatory agent P P becatecarin antineoplastic agent TOP2A becatecarin antineoplastic agent TOP2B beclomethasone antiinflammatory R3C1 agent, glucocorti coi dbeclomethasone antiinflammatory R3C1 agent, glucocorti coi dbeclomethasone antiinflammatory R3C1 agent, glucocorti coi dbuprenorphine antidepressant, analgesic,for OPRK1 treatment of opioid addictionbuprenorphine antidepressant, analgesic,for OPRM1 treatment of opioid addictionfentanyl analgesic OPRD1 fentanyl analgesic OPRM1 benazepril antihypertensive agent ACE bepotastine antiallergy agent HRH1Drug Name Indication(s) Gene beraprost antihypertensive agent PTGIR betamethasone antiinflammatory NR3C1 agent, glucocorti coi dbetamethasone antiinflammatory NR3C1 agent, glucocorti coi dbetrixaban antithrombotic F10 bexarotene antineoplastic agent RXRA bexarotene antineoplastic agent RXRB bexarotene antineoplastic agent RXRGBF-1 antimigraine agent HTR2BBF-Derml antiallergy agent HDCBG-9928 for treatment of congestive heart AD OR A 1 failurefluoxetine for treatment of sleep apnea SLC6A4 ondansetron for treatment of sleep apnea HTR3ABGC20-1531 antimigraine agent PTGER4BGG-492 anti convul sant, antimigrai ne agent GRIA1BGG-492 anti convul sant, antimigrai ne agent GRIA2BGG-492 anti convul sant, antimigrai ne agent GRIA3BGG-492 anti convul sant, antimigrai ne agent GRIA4 progesterone neuroprotectant for stroke victims ESR1 progesterone neuroprotectant for stroke victims NR3C2 progesterone neuroprotectant for stroke victims PGRBI- 10773 antidiabetic SLC5A2 olodaterol bronchodilator ADRB2Nintedanib antineoplastic agent FGFR1Nintedanib antineoplastic agent FGFR2Nintedanib antineoplastic agent FGFR3Drug Name Indication(s) GeneNintedanib antineoplastic agent FLT1Nintedanib antineoplastic agent FLT4Nintedanib antineoplastic agent KDRNintedanib antineoplastic agent PDGFRANintedanib antineoplastic agent PDGFRBBicalutamide antineoplastic agent AR bifeprunox antipsychotic agent, antiparkinson DRD2 agentbifeprunox antipsychotic agent, antiparkinson DRD3 agentbifeprunox antipsychotic agent, antiparkinson HTR1A agentbifeprunox antipsychotic agent, antiparkinson HTR2A agentbifeprunox antipsychotic agent, antiparkinson HTR2C agentbifeprunox antipsychotic agent, antiparkinson HTR7 agentBIM23A760 antineoplastic agent,treatment for DRD2 acromegalyBIM23A760 antineoplastic agent,treatment for SSTR2 acromegalyBIM23A760 antineoplastic agent,treatment for SSTR5 acromegalybimatoprost antiglaucomic agent PTGER1 bimatoprost antiglaucomic agent PTGER3 bimatoprost antiglaucomic agent PTGFR bimoclomol for treatment of diabetic neuropathy HSF1Drug Name Indication(s) Gene 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 menopauseestradiol hormone replacement, treatment for ESR2 menopausetestosterone hormone replacement AR dapagliflozin antidiabetic SLC5A2BMS-582949 antiinflammatory MAPK11 agent,DM ARD, antip son ati cBMS-582949 antiinflammatory MAPK12 agent,DM ARD, antip son ati cBMS-582949 antiinflammatory MAPK13 agent,DM ARD, antip sori ati cBMS-582949 antiinflammatory MAPK14 agent,DM ARD, antip sori ati cBMS-299897 for treatment of alzheimer's disease APH1ABMS-299897 for treatment of alzheimer's disease APH1BBMS-299897 for treatment of alzheimer's disease NCSTNBMS-299897 for treatment of alzheimer's disease PSEN1BMS-299897 for treatment of alzheimer's disease PSEN2BMS-299897 for treatment of alzheimer's disease PSE ENBMS-708163 for treatment of alzheimer's disease APHIABMS-708163 for treatment of alzheimer's disease APHIBDrug Name Indication(s) GeneBMS-708163 for treatment of alzheimer's disease NCSTNBMS-708163 for treatment of alzheimer's disease PSEN1BMS-708163 for treatment of alzheimer's disease PSEN2BMS-708163 for treatment of alzheimer's disease PSE ENBMS-754807 antineoplastic agent IGF1RBMS-863233 antineoplastic agent CDC7 calcitonin antiosteoporotic agent CALCRNCX116 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 ADRB2Brivaracetam anticonvulsant SV2A bromfenac opthalmological agent,NSAID PTGS1 bromfenac opthalmological agent,NSAID PTGS2 bromocriptine antidiabetic DRD2 bromocriptine antidiabetic DRD3Bryostatin for treatment of alzheimer's disease PRKCABryostatin for treatment of alzheimer's disease PRKCBBryostatin for treatment of alzheimer's disease PRKCDBryostatin for treatment of alzheimer's disease PRKCEBryostatin for treatment of alzheimer's disease PRKCGBryostatin for treatment of alzheimer's disease PRKCHBryostatin for treatment of alzheimer's disease PRKCQBryostatin for treatment of alzheimer's disease PRKD1Bryostatin for treatment of alzheimer's disease PRKD2Drug Name Indication(s) GeneBryostatin for treatment of alzheimer's disease PRKD3Bryostatin-1 antineoplastic agent PRKCABryostatin- 1 antineoplastic agent PRKCBBryostatin-1 antineoplastic agent PRKCDBryostatin-1 antineoplastic agent PRKCEBryostatin-1 antineoplastic agent PRKCGBryostatin-1 antineoplastic agent PRKCHBryostatin-1 antineoplastic agent PRKCQBryostatin-1 antineoplastic agent PRKD1Bryostatin-1 antineoplastic agent PRKD2Bryostatin-1 antineoplastic agent PRKD3 fentanyl analgesic OPRD1 fentanyl analgesic OPRM1 prochlorperazine antiemetic DRD2 bucindolol for treatment of heart failure ADRB 1 bucindolol for treatment of heart failure ADRB2 budesonide antiinflammatory R3C1 agent, glucocorti coi dFormoterol bronchodilator ADRB2 budesonide antiinflammatory R3C1 agent, glucocorti coi dbudesonide antiinflammatory R3C1 agent, glucocorti coi dbudesonide antiinflammatory R3C1 agent, glucocorti coi dbudesonide antiinflammatory R3C1 agent, glucocorti coi dDrug Name Indication(s) Gene budesonide antiinflammatory R3C1 agent, glucocorti coi dbudesonide antiinflammatory R3C1 agent, glucocorti coi dbudiodarone antiarrhytmic agent ADRB 1 budiodarone antiarrhytmic agent CACNA2D2 budiodarone antiarrhytmic agent KC H2 buprenorphine antidepressant, analgesic,for OPRK1 treatment of opioid addictionbuprenorphine antidepressant, analgesic,for OPRM1 treatment of opioid addictionnaloxone analgesic OPRK1 naloxone analgesic OPRM1 buprenorphine antidepressant, analgesic,for OPRK1 treatment of opioid addictionbuprenorphine antidepressant, analgesic,for OPRM1 treatment of opioid addictionnaloxone for treatment of opioid addiction OPRK1 naloxone for treatment of opioid addiction OPRM1 buprenorphine antidepressant, analgesic,for OPRK1 treatment of opioid addictionbuprenorphine antidepressant, analgesic,for OPRM1 treatment of opioid addictionbuprenorphine antidepressant, analgesic,for OPRK1 treatment of opioid addictionbuprenorphine antidepressant, analgesic,for OPRM1 treatment of opioid addictionDrug Name Indication(s) Gene buprenorphine antidepressant, analgesic,for OPRK1 treatment of opioid addictionbuprenorphine antidepressant, analgesic,for OPRM1 treatment of opioid addictionbupropion anti depres sant, app eti te SLC6A2 suppressant, smoking-cessati on agentbupropion anti depres sant, app eti te SLC6A3 suppressant, smoking-cessati on agentBVT. l 15959 analgesic ADORA2ABVT.28949 for treatment of glaucoma HTR2A amphetamine for treatment of cognitive CARTPT dysfunction, for treatment of ADHDamphetamine for treatment of cognitive SLC18A2 dysfunction, for treatment of ADHDamphetamine for treatment of cognitive SLC6A3 dysfunction, for treatment of ADHDamphetamine for treatment of cognitive TAAR1 dysfunction, for treatment of ADHDC-1311 antineoplastic agent TOPIC-1311 antineoplastic agent TOP2A cabazitaxel antineoplastic agent TUBA4A cabazitaxel antineoplastic agent TUBB1 amlodipine antihypertensive agent, CACNA1C cardiovascular agentamlodipine antihypertensive agent, CACNA1D cardiovascular agentamlodipine antihypertensive agent, CACNA1 S cardiovascular agentDrug Name Indication(s) Gene amlodipine antihypertensive agent, CACNA2D1 cardiovascular agentamlodipine antihypertensive agent, CAC B2 cardiovascular agentatorvastatin anticholesterolaemic agent HMGCRCAL-101 antineoplastic agent PIK3CD betamethasone antiinflammatory R3C1 agent, glucocorti coi dcalcipotriene antipsoriatic agent VDR calcitriol antipsoriatic agent VDR buprenorphine antidepressant, analgesic,for OPRK1 treatment of opioid addictionbupreno hine antidepressant, analgesic,for OPRM1 treatment of opioid addictionCanagliflozin antidiabetic SLC5A2 candesartan antihypertensive agent AGTR1 cangrelor antithrombotic P2RY12PRS-211375 analgesic C R2CAP7.1 antineoplastic agent TOP2ACaprospinol for treatment of alzheimer's disease APPCarfilzomib antineoplastic agent PSMB1Carfilzomib antineoplastic agent PSMB2Carfilzomib antineoplastic agent PSMB5 cariprazine antipsychotic agent DRD2 cariprazine antipsychotic agent DRD3 carvedilol for treatment of congestive heart ADRA1A failurecarvedilol cardiovascular agent ADRB1Drug Name Indication(s) Gene carvedilol cardiovascular agent ADRB2Casopitant antiemetic TACR1 dronabinol analgesic CNR1 dronabinol analgesic CNR2CB-03-01 dermatological agent AR caricotamide antineoplastic agent NQ02 tretazicar antineoplastic agent DNA abiraterone antineoplastic agent CYP17A1JNK-401 antineoplastic agent MAPK10JNK-401 antineoplastic agent MAPK8JNK-401 antineoplastic agent MAPK9CCX025 antiinflammatory agent CCR9CCX140 anti i nfl amm atory agent, anti di ab eti c CCR2CCX168 antiinflammatory agent,for treatment C5AR1 for autoimmune diseaseCCX282 antiinflammatory agent,for treatment CCR9 of Chron's disease,for treatment ofulceraite colitisCCX354 antiinflammatory agent,DMARD CCR1CCX832 antiinflammatory agent,for treatment CMKLR1 for autoimmune diseasefenofibrate anticholesterolaemic agent PPARA azelastine antiallergy agent HRH1 budesonide antiinflammatory NR3C1 agent, glucocorti coi dcediranib antineoplastic agent FLT1 cediranib antineoplastic agent FLT4 cediranib antineoplastic agent KDRDrug Name Indication(s) Gene celecoxib NSAID PTGS2 mycophenolate mofetil immunosuppressant IMPDH1 mycophenolate mofetil immunosuppressant IMPDH2 synthetic conjugated estrogens for treatment of postmenopausal ESR1 symptomssynthetic conjugated estrogens for treatment of postmenopausal ESR2 symptomshistamine cytorprotective agent during cancer HRH2 treatmentCER-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 HRH1CF-101 antiinflammatory agent,DMARD AD OR A3CF-102 antineoplastic agent AD OR A3CGI 00649 NSAID CA1CGI 00649 NSAID PTGS2 clopidogrel antiplatelet agent P2RY12 omeprazol antiulcer agent ATP4ACH-1504 antiinflammatory agent,DMARD DHFRCHF 4227 antiosteoporotic agent ESR1Drug Name Indication(s) GeneCHF 4227 antiosteoporotic agent ESR2 beclomethasone antiinflammatory R3C1 agent, glucocorti coi dformoterol antiasthmatic agent ADRB2 chidamide antineoplastic agent HDAC1 chidamide antineoplastic agent HDAC10 chidamide antineoplastic agent HDAC2 chidamide antineoplastic agent HDAC3CHIR-265 antineoplastic agent BRAFCHIR-265 antineoplastic agent KDRCHIR-265 antineoplastic agent RAF 1 cyclosporine immunosuppressant CAMLG cyclosporine immunosuppressant PPP3R2 tadalafil for treatment of erectile dysfunction PDE5A cilansetron for treatment of irritable bowel HTR3A syndromecimicoxib 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.Drug Name Indication(s) Gene tiramsetiv for treatment of skeletal muscle TNNI2 disorders associated with aging andneuro-degenerative disorders.tiramsetiv for treatment of skeletal muscle TNNT1 disorders associated with aging andneuro-degenerative disorders.tiramsetiv for treatment of skeletal muscle TNNT2 disorders associated with aging andneuro-degenerative disorders.clazosentan for treatment and prevention of EDNRA vasospasmclevidipine antihypertensive agent CACNA1C clevidipine antihypertensive agent CACNA1D clevidipine antihypertensive agent CACNA1F clevidipine antihypertensive agent CACNA1 S clobazam anxi olyti c, anti convul sant GABRA1 clobazam anxi olyti c, anti convul sant GABRA2 clobazam anxi olyti c, anti convul sant GABRA3 clobazam anxi olyti c, anti convul sant GABRA4 clobazam anxi olyti c, anti convul sant GABRA5 clobazam anxi olyti c, anti convul sant GABRA6 clobazam anxi olyti c, anti convul sant GABRB1 clobazam anxi olyti c, anti convul sant GABRB2 clobazam anxi olyti c, anti convul sant GABRB3 clobazam anxi olyti c, anti convul sant GABRD clobazam anxi olyti c, anti convul sant GABRE clobazam anxi olyti c, anti convul sant GABRG1 clobazam anxi olyti c, anti convul sant GABRG2Drug Name Indication(s) Gene clobazam anxi olyti c, anti convul sant GABRG3 clobazam anxi olyti c, anti convul sant GABRP clobazam anxi olyti c, anti convul sant GABRQ clobazam anxi olyti c, anti convul sant GABRR1 clobazam anxi olyti c, anti convul sant GABRR2 clobazam anxi olyti c, anti convul sant GABRR3 clobetasol antiinflammatory R3C1 agent, corti costeroi dclodronate antineoplastic agent SLC25A4 clodronate antineoplastic agent SLC25A5 clodronate antineoplastic agent SLC25A6Clofarabine antineoplastic agent POLA1Clofarabine antineoplastic agent RRM1 clonidine for treatment of diabetic ADRA2A neuropathy,for treatment ofADHD,antimucositicclonidine for treatment of diabetic ADRA2B neuropathy,for treatment ofADHD,antimucositicclonidine for treatment of diabetic ADRA2C neuropathy,for treatment ofADHD,antimucositicclonidine for treatment of diabetic ADRA2A neuropathy,for treatment ofADHD,antimucositicclonidine for treatment of diabetic ADRA2B neuropathy,for treatment ofADHD,antimucositicDrug Name Indication(s) Gene clonidine for treatment of diabetic ADRA2C neuropathy,for treatment ofADHD,antimucositicCLX-0921 antidiabetic PPARGCM2489 antiinflammatory agent,antipsoriatic ORA1C DO101 antineoplastic agent TOP2AC FIOIO antineoplastic agent HSP90AA1C FIOIO antineoplastic agent HSP90AB1CNS-5161 analgesic GRIN1CNS-5161 analgesic GRIN2ACNS-5161 analgesic GRIN2BCNS-5161 analgesic GRIN2CCNS-5161 analgesic GRIN2DCNS-5161 analgesic GRIN3ACNS-5161 analgesic GRIN3BCNS-7056 sedative GABRA2CNS-7056 sedative GABRA3CNS-7056 sedative GABRA5CNS-7056 sedative GABRA6CNS-7056 sedative GABRB1CNS-7056 sedative GABRB1CNS-7056 sedative GABRB2CNS-7056 sedative GABRB2CNS-7056 sedative GABRB3CNS-7056 sedative GABRDCNS-7056 sedative GABRDCNS-7056 sedative GABRECNS-7056 sedative GABRG1Drug Name Indication(s) GeneCNS-7056 sedative GABRG2CNS-7056 sedative GABRG3CNS-7056 sedative GABRG3CNS-7056 sedative GABRPCNS-7056 sedative GABRQCNS-7056 sedative GABRR2CNV2197944 analgesic CACNA1B oxycodone analgesic OPRD1 oxycodone analgesic OPRK1 oxycodone analgesic OPRM1 oxycodone analgesic OPRD1 oxycodone analgesic OPRK1 oxycodone analgesic OPRM1COL-3 antineoplastic agent MMP2COL-3 antineoplastic agent MMP9 colchicine for treatment of gout TUBB bupivacaine 1 ocal anestethi c, anal gesi c, neural gi a SCN10A conivaptan for treatment of hyponatremia AVPR1A conivaptan for treatment of hyponatremia AVPR2 estrogen for symptomatic treatment of ESR1 menopausal symptomsestrogen for symptomatic treatment of ESR2 menopausal symptomsprogesterone for symptomatic treatment of ESR1 menopausal symptomsprogesterone for symptomatic treatment of NR3C2 menopausal symptomsDrug Name Indication(s) Gene progesterone for symptomatic treatment of PGR menopausal symptomsethinyl estradiol contraceptive ESR1 gestodene contraceptive PGR bupropion anti depres sant, app eti te SLC6A2 suppressant, smoking-cessati on agent bupropion anti depres sant, app eti te SLC6A3 suppressant, smoking-cessati on 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 DNTTCORT 108297 for prevention of weight gain during R3C1 antipsychotic treatmentCP-4126 antineoplastic agent DNACP-609,754 antineoplastic agent FNTACP-609,754 antineoplastic agent FNTBCPG 10101 immunostimulant TLR9CPG 52364 antiinflammatory agent TLR7CPG 52364 antiinflammatory agent TLR8CPG 52364 antiinflammatory agent TLR9CPI-613 antineoplastic agent PDHA1CPI-613 antineoplastic agent PDHA2CPI-613 antineoplastic agent PDHBCPI-613 antineoplastic agent PDK1Drug Name Indication(s) GeneCPI-613 antineoplastic agent PDK2CPI-613 antineoplastic agent PDK3CPI-613 antineoplastic agent PDK4 semapimod antiinflammatory agent,for treatment MAPK11 of Chron's diseasesemapimod antiinflammatory agent,for treatment MAPK12 of Chron's diseasesemapimod antiinflammatory agent,for treatment MAPK13 of Chron's diseasesemapimod antiinflammatory agent,for treatment MAPK14 of Chron's diseasefloxuridine antineoplastic agent TYMS irinotecan antineoplastic agent TOPI irinotecan antineoplastic agent TOP1MT cytarabine antineoplastic agent POLB daunorubicin antineoplastic agent TOP2A daunorubicin antineoplastic agent TOP2BCR665 analgesic OPRK1CR845 analgesic OPRK1 pravastatin antihypecholesterolemic agent HMGCR rosuvastatin antihypecholesterolemic agent HMGCR561679 antidepressant CRHR1 crizotinib antineoplastic agent ALK crizotinib antineoplastic agent METCRTH2 receptor antagonist antiallergy agent GPR44 prednisolone antiinflammatory R3C1 agent, corti costeroi ddipyridamole anticoagulant ADADrug Name Indication(s) Gene dipyridamole anticoagulant PDE10A dipyridamole anticoagulant PDE4A dipyridamole anticoagulant PDE5A amoxapine antidepressant SLC6A2 amoxapine antidepressant SLC6A4 prednisolone antiinflammatory R3C1 agent, corti costeroi dparoxetine antidepressant SLC6A4 prednisolone antiinflammatory R3C1 agent, corti costeroi damoxapine antidepressant SLC6A2 amoxapine antidepressant SLC6A4 dipyridamole antithrombotic ADA dipyridamole antithrombotic PDE10A dipyridamole antithrombotic PDE4A dipyridamole antithrombotic PDE5A budesonide antiinflammatory R3C1 agent, glucocorti coi dnortriptyline antiasthmatic agent SLC6A2 nortriptyline antiasthmatic agent SLC6A4 mometasone antiinflammatory R3C1 agent, glucocorti coi dnortriptyline antidepressant SLC6A2 nortriptyline antidepressant SLC6A4 bezafibrate antidiabetic PPARA diflunisal antidiabetic PTGS1 diflunisal antidiabetic PTGS2CS-3030 anticoagulant F10Drug Name Indication(s) GeneCS-7017 antineoplastic agent PPARG amlodipine antihypertensive agent CACNA1C amlodipine antihypertensive agent CACNA1D amlodipine antihypertensive agent CACNA1 S amlodipine antihypertensive agent CACNA2D1 amlodipine antihypertensive agent CAC B2 olmesartan antihypertensive agent AGTR1CTA018 antiinflammatory agent,antipsoriatic CYP24A1CTS-21166 for treatment of Alzheimer's disease BACE1CUDC-101 antineoplastic agent EGFRCUDC-101 antineoplastic agent ERBB2CUDC-101 antineoplastic agent HDAC1CUDC-101 antineoplastic agent HDAC10CUDC-101 antineoplastic agent HDAC11CUDC-101 antineoplastic agent HDAC2CUDC-101 antineoplastic agent HDAC3CUDC-101 antineoplastic agent HDAC4CUDC-101 antineoplastic agent HDAC5CUDC-101 antineoplastic agent HDAC6CUDC-101 antineoplastic agent HDAC7CUDC-101 antineoplastic agent HDAC8CUDC-101 antineoplastic agent HDAC9CVT-3619 antihyperlipidemic agent AD OR A 1CVT-6883 antiasthmatic agent ADORA2BCX157 antidepressant MAOACX1632 / S 47445 for treatment of Alzheimer's disease GRIA1CX1632 / S 47445 for treatment of Alzheimer's disease GRIA2CX1632 / S 47445 for treatment of Alzheimer's disease GRIA3Drug Name Indication(s) GeneCX1632 / S 47445 for treatment of Alzheimer's disease GRIA4CX-4945 antineoplastic agent CS K2A1CX717 for treatment of Alzheimer's disease GRIA1CX717 for treatment of Alzheimer's disease GRIA2CX717 for treatment of Alzheimer's disease GRIA3CX717 for treatment of Alzheimer's disease GRIA4CXB909 for treatment of chemotherapy- LNGFR induced peripheral neuropathyCXB909 for treatment of chemotherapy- NTRK1 induced peripheral neuropathyCYC116 antineoplastic agent AURKACYC116 antineoplastic agent AURKBCYC116 antineoplastic agent KDR cyclosporine immunosuppressant CAMLG cyclosporine immunosuppressant PPP3R2 duloxetine antidepressant SLC6A2 duloxetine antidepressant SLC6A4 cysteamine for treatment of corneal cystine cystine accumulationcytarabine antineoplastic agent POLBD3263 antineoplastic agent TRPM8Dabigatran anticoagulant F2 decitabine antineoplastic agent DNMT1 dapoxetine for treatment of premature SLC6A4 ejaculationdarapladib antiinflammatory agent,DMARD PLA2G7 darifenacin for treatment of overactive bladder CHRM3 darusentan antihypertensive agent ED RADrug Name Indication(s) Gene 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 SLC6A3DB-959 antidiabetic PPARDDB-959 antidiabetic PPARG diazoxide choline antidyslipidaemic agent ABCC8DDP225 for treatment of irritable bowel HTR3A syndromeDDP225 for treatment of irritable bowel HTR3B syndromeDDP225 for treatment of irritable bowel HTR3C syndromeDDP225 for treatment of irritable bowel HTR3D syndromeDDP225 for treatment of irritable bowel HTR3E syndromeDDP225 for treatment of irritable bowel SLC6A2 syndromeDebio 0932 antineoplastic agent HSP90AA1Debio 0932 antineoplastic agent HSP90AB1Drug Name Indication(s) GeneDEBIO-9902 SR for treatment of Alzheimer's disease ACHEDegarelix antineoplastic agent GNRHRDegarelix antineoplastic agent GNRHR2 denufosol for treatment of cystic fibrosis P2RY2 deoxynoj irimycin for treatment of Pompe disease GAA bupivacaine 1 ocal anestethi c, anal gesi c, neural gi a 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 colitisdersalazine antiinflammatory agent,for treatment PTGS2 of ulcerative colitisdersalazine antiinflammatory agent,for treatment TNFof ulcerative colitisdesloratadine antiallergy agent HRH1Drug Name Indication(s) Gene desonide antiinflammatory R3C1 agent, corti costeroi ddexamethasone antiinflammatory R3C1 agent, glucocorticoid, for treatment ofMeniere's diseaseDexanabinol neuroprotectant GRIN1Dexanabinol neuroprotectant GRIN2ADexanabinol neuroprotectant GRIN2BDexanabinol neuroprotectant GRIN2DDexanabinol neuroprotectant GRIN3ADexanabinol 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 prophylaxisDG041 Platelet Aggregation Inhibitor PTGER3DG051 antiinflammatory agent,myocardial LTA4H infarction prophylaxisDG071 for treatment of alzheimer's disease PDE4ADG071 for treatment of alzheimer's disease PDE4BDG3173 hormone replacement SSTR1DG3173 hormone replacement SSTR2Drug Name Indication(s) GeneDG3173 hormone replacement SSTR4DG3173 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 PTGS2Diclofenac analgesic PTGS1Diclofenac analgesic PTGS2Diclofenac analgesic PTGS1Diclofenac analgesic PTGS2Diclofenac NSAID PTGS1Diclofenac NSAID PTGS2Diclofenac for treatment of glaucoma PTGS1Drug Name Indication(s) GeneDiclofenac for treatment of glaucoma PTGS2 difluprednate antiinflammatory R3C1 agent, corti costeroi ddiltiazem 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 GRIN2DDIO-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 VDRDocetaxel antineoplastic agent BCL2Docetaxel antineoplastic agent TBB1 dolasetron antiemetic HTR3ADrug Name Indication(s) Gene dolasetron antiemetic HTR3B dolasetron antiemetic HTR3C dolasetron antiemetic HTR3D dolasetron antiemetic HTR3E donepezil for treatment of alzheimer's disease ACHE beclomethasone dipropionate antiinflammatory R3C1 agent, glucocorti coi dDOV 102,677 antidepressant SLC6A2DOV 102,677 antidepressant SLC6A3DOV 102,677 antidepressant SLC6A4DOV 216,303 antidepressant SLC6A2DOV 216,303 antidepressant SLC6A3DOV 216,303 antidepressant SLC6A4DOV 21947 antidepressant SLC6A2DOV 21947 antidepressant SLC6A3DOV 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 SLC6A4Drug Name Indication(s) Gene doxercalciferol for treatment of secondary VDR hyperparathyroidismdoxorubicin antineoplastic agent TOP2A doxorubicin antineoplastic agent TOP2A doxorubicin antineoplastic agent TOP2A doxorubicin antineoplastic agent TOP2ADP-VPA anticonvulsant ABATDRF 10945 antidyslipidaemic agent PPARA dronabinol appetite stimulant C R1 drospirenone hormone replacement PGR estradiol hormone replacement ESR1 estradiol hormone replacement ESR2DSC-103 antiosteoporotic agent VDRDTS-201 antineoplastic agent TOP2A bupivacaine 1 ocal anestethi c, anal gesi c, neural gi a SCN10A bupivacaine 1 ocal anestethi c, anal gesi c, neural gi a SCN10A sildenafil for treatment of erectile dysfunction PDE5A dutasteride for treatment of benign prostate SRD5A1 hyperplasiadutasteride for treatment of benign prostate SRD5A2 hyperplasiatamsulosin for treatment of benign prostatic ADRA1A hyperplasiadutasteride for treatment of benign prostate SRD5A1 hyperplasiadutogliptin antidiabetic DPP4 azelastine antiallergy agent HRH1Drug Name Indication(s) Gene fluticasone antiinflammatory R3C1 agent, glucocorti coi dperampanel anticonvulsant GRIA1 perampanel anticonvulsant GRIA2 perampanel anticonvulsant GRIA3 perampanel anticonvulsant GRIA4E2012 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 gamblingedoxaban antithrombotic F10 venlafaxine antidepressant SLC6A2 venlafaxine antidepressant SLC6A4 eflorni thine for treatment of unwanted facial hair ODC1 in womendexamethasone antiinflammatory R3C1 agent, glucocorticoid, for treatment ofMeniere's diseaseEtazolate for treatment of alzheimer's disease GABRA2Drug Name Indication(s) GeneEtazolate for treatment of alzheimer's disease GABRA3Etazolate for treatment of alzheimer's disease GABRB1Etazolate for treatment of alzheimer's disease GABRB2Etazolate for treatment of alzheimer's disease GABREEtazolate for treatment of alzheimer's disease GABRG1Etazolate for treatment of alzheimer's disease PDE4AEtazolate for treatment of alzheimer's disease PDE4BEtazolate for treatment of alzheimer's disease PDE4CEtazolate for treatment of alzheimer's disease PDE4D ronomilast antiinflammatory agent PDE4A ronomilast antiinflammatory agent PDE4BED-71 antiosteoporotic agent VDR oxycodone analgesic OPRD1 oxycodone analgesic OPRK1 oxycodone analgesic OPRM1 eliglustat for treatment of Gaucher' s disease UGCG elinogrel antiplatelet agent P2RY12Elocalcitol for treatment of benign prostatic VDRhyperplasiabupropion anti depres sant, app eti te SLC6A2 suppressant, smoking-cessati on agentbupropion anti depres sant, app eti te SLC6A3 suppressant, smoking-cessati on agentzonisamide appetite suppressant CACNA1G zonisamide appetite suppressant CACNA1H zonisamide appetite suppressant CACNA1I zonisamide appetite suppressant SCN11A zonisamide appetite suppressant SCN1ADrug Name Indication(s) Gene 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 CACNA1 S felodipine antihypertensive agent CACNA2D1 felodipine antihypertensive agent CACNANB2 paclitaxel antineoplastic agent BCL2 paclitaxel antineoplastic agent TUBB1 eniluracil antineoplastic agent DPYDE MD-1198 antineoplastic agent HIF1AE MD-2076 antineoplastic agent ABLlE MD-2076 antineoplastic agent AURKAENMD-2076 antineoplastic agent BLKENMD-2076 antineoplastic agent CSF1RENMD-2076 antineoplastic agent FGFR1ENMD-2076 antineoplastic agent FGFR2ENMD-2076 antineoplastic agent FLT3ENMD-2076 antineoplastic agent FLT4ENMD-2076 antineoplastic agent FYNDrug Name Indication(s) GeneE MD-2076 antineoplastic agent JAK2E MD-2076 antineoplastic agent KDRENMD-2076 antineoplastic agent KITENMD-2076 antineoplastic agent LCKENMD-2076 antineoplastic agent NTRK1ENMD-2076 antineoplastic agent PDGFRAENMD-2076 antineoplastic agent PTK2ENMD-2076 antineoplastic agent RETENMD-2076 antineoplastic agent SRCENMD-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 HDAC3Enzastaurin antineoplastic agent PRKCBEP217609 anticoagulant F10EP217609 anticoagulant F2EP42675 anticoagulant F10EP42675 anticoagulant F2EPI-743 for treatment of Chron's disease,for NQOl treatment of ulcerative colitisepinastine antiallergy agent HRH1Drug Name Indication(s) Gene epinastine antiallergy agent HRH2 eplerenone antihypertensive agent R3C2 eplivanserine for treatment of insomnia HTR2A eplivanserine for treatment of insomnia HTR2CEpothilone D antineoplastic agent TUBB1 eprotirome antidyslipidaemic agent THRB erdosteine for treatment of chronic obstructive ELA E pulmonary disorder (COPD)eritoran for treatment of sepsis TLR4Eslicarbazepine anticonvulsant SCN5A esmirtazapine for treatment of insomnia,for ADRA2A treatment of menopausal symptomsesmirtazapine for treatment of insomnia,for HTR2A treatment of menopausal symptomsesmirtazapine for treatment of insomnia,for HTR3A treatment of menopausal symptomsesomeprazole Proton pump inhibitor ATP4A estradiol contraceptive ESR1 estradiol contraceptive ESR1 estradiol contraceptive ESR2 norethisterone contraceptive PGR estradiol for treatment of menopausal ESR1 symptomsestradiol for treatment of menopausal ESR2 symptomsestradiol for treatment of menopausal ESR1 symptomsDrug Name Indication(s) Gene estradiol for treatment of menopausal ESR2 symptomsestradiol contraceptive ESR1 dienogest contraceptive ESR1 dienogest contraceptive PGR estradiol contraceptive ESR2 estradiol contraceptive ESR2 estradiol for treatment of menopausal ESR1 symptomsestradiol for treatment of menopausal ESR2 symptomslevonorgestrel for treatment of menopausal ESR1 symptomslevonorgestrel for treatment of menopausal PGR symptomslevonorgestrel for treatment of menopausal SRD5A1 symptomsestradiol for treatment of menopausal ESR1 symptomsestradiol for treatment of menopausal ESR2 symptomsestradiol for treatment of menopausal ESR1 symptomsestradiol for treatment of menopausal ESR2 symptomsdrospirenone contraceptive AR drospirenone contraceptive R3C2 drospirenone contraceptive PGRDrug Name Indication(s) Gene 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 PTGS2EV-077-3201-2TBS antidiabetic PPARG everolimus immunosuppressant MTOR raloxifen for treatment of menopausal ESR1 symptomsraloxifen for treatment of menopausal ESR2 symptomsmetoclopramide for treatment of diabetic CHRM1 gastroparesismetoclopramide for treatment of diabetic DRD2 gastroparesisEVP-6124 nootropic CHRNA7Drug Name Indication(s) GeneEVT-101 antidepressant GRIN2BEVT-103 antidepressant GRIN2BEVT-201 hypnotic GABRA2EVT-201 hypnotic GABRA3EVT-201 hypnotic GABRA5EVT-201 hypnotic GABRA6EVT-201 hypnotic GABRB1EVT-201 hypnotic GABRB1EVT-201 hypnotic GABRB2EVT-201 hypnotic GABRB2EVT-201 hypnotic GABRB3EVT-201 hypnotic GABRDEVT-201 hypnotic GABRDEVT-201 hypnotic GABREEVT-201 hypnotic GABRG1EVT-201 hypnotic GABRG2EVT-201 hypnotic GABRG3EVT-201 hypnotic GABRG3EVT-201 hypnotic GABRPEVT-201 hypnotic GABRQEVT-201 hypnotic GABRR2EVT-302 smoking-cessation agent MAOBEVT-401 antiinflammatory agent P2RX7Exebryl-1 for treatment of alzheimer's disease APPExebryl-1 for treatment of alzheimer's disease MAPT exemestane antineoplastic agent CYP19A1 ezatiostat for treatment of Myelodysplastic GSTP1SyndromeDrug Name Indication(s) GenePEG-SN38 antineoplastic agent TOP1MTPEG-SN38 antineoplastic agent TOPI fentanyl analgesic OPRD1 fentanyl analgesic OPRM1 febuxostat for treatment of gout XDH felodipine antihypertensive agent CACNA1C felodipine antihypertensive agent CACNA1D felodipine antihypertensive agent CACNA1 S felodipine antihypertensive agent CACNA2D1 felodipine antihypertensive agent CAC B2 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 OPRD1Drug Name Indication(s) Gene fentanyl analgesic OPRM1 fentanyl analgesic OPRD1 fentanyl analgesic OPRM1 fesoterodine for treatment of overactive bladder CHRM3 syndromefexofenadine antiallergy agent HRH1 pseudoephedrine antiallergy agent ADRA 1 A pseudoephedrine antiallergy agent ADRA2A pseudoephedrine antiallergy agent SLC6A2 pseudoephedrine antiallergy agent SLC6A3 pseudoephedrine antiallergy agent SLC6A4FG-2216 for treatment of anemia EGLN1FG-2216 for treatment of anemia EGLN2FG-2216 for treatment of anemia EGLN3FG-4592 for treatment of anemia EGLN1FG-4592 for treatment of anemia EGLN2FG-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 angioedemafispemifene hormone replacement ESR1 fispemifene hormone replacement ESR2FK352B antihypertensive agent AD OR A 1 alvocidib antineoplastic agent CDC2 alvocidib antineoplastic agent CDK10Drug Name Indication(s) Gene 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 dysfunctionflibanserin for treatment of female sexual HTR2A dysfunctionflovagatran anticoagulant F2 fludarabine antineoplastic agent DCK fludarabine antineoplastic agent POLA1 fludarabine antineoplastic agent RRM1 flunisolide antiinflammatory R3C1 agent, glucocorti coi dflunisolide antiinflammatory R3C1 agent, glucocorti coi dfluocinonide antiinflammatory R3C1 agent, glucocorti coi dfluoxetine antidepressant SLC6A4 flupirtine analgesic KCNJ3 flupirtine analgesic KCNJ5 flupirtine analgesic KCNJ6 flupirtine analgesic KCNJ9Drug Name Indication(s) Gene fluticasone antiinflammatory R3C1 agent, glucocorti coi dfluvastatin 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 R3C1 agent, corti costeroi dfrovatriptan antimigraine agent HTR1B frovatriptan antimigraine agent HTR1D fruquintinib antineoplastic agent FLT1 fruquintinib antineoplastic agent FLT4 fruquintinib antineoplastic agent KDR dexamethasone antiinflammatory R3C1 agent, glucocorticoid, for treatment ofMeniere's diseasefulvestrant antineoplastic agent ESR1 leucovorin adjuvant to chemotherapy TYMSDrug Name Indication(s) GeneFX125L antiasthmatic agent CCR1FX125L antiasthmatic agent CXCR1FX125L antiasthmatic agent CXCR2FX125L 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 GABRA6Drug Name Indication(s) Gene gantacurium muscle relaxant,neuromuscular CHRNA2 blocking agentGDC-0068 antineoplastic agent AKT1GDC-0068 antineoplastic agent AKT2GDC-0068 antineoplastic agent AKT3GDC-0973 antineoplastic agent MAP2K1 gemcitabine antineoplastic agent RRM1 gepirone antidepressant HTR1A progesterone for prevention of preterm delivery PGRGGTI-2418 antineoplastic agent FNTAGGTI-2418 antineoplastic agent PGGT1BGL1001 for treatment of Chron's disease,for ACE2treatment of ulcerative colitisglimepiride antidiabetic KCNJ1 glimepiride antidiabetic ABCC8 glimepiride antidiabetic KCNJ11GLPG0187 antineoplastic agent ITGA5GLPG0187 antineoplastic agent ITGAVGLPG0187 antineoplastic agent ITGB1GLPG0187 antineoplastic agent ITGB3GLPG0187 antineoplastic agent ITGB5GLPG0187 antineoplastic agent ITGB6GLPG0259 antiinflammatory agent,DMARD MAPKAPK5GLPG0492 for treatment of cachexia ARGLPG0634 antiinflammatory agent,DMARD JAK1GLPG0634 antiinflammatory agent,DMARD JAK2Glufosfamide antineoplastic agent SLC2A1Glufosfamide antineoplastic agent SLC2A2Drug Name Indication(s) GeneGlufosfamide antineoplastic agent SLC2A3Glufosfamide antineoplastic agent SLC2A4Glufosfamide antineoplastic agent SLC2A5Glufosfamide antineoplastic agent SLC5A1Glufosfamide antineoplastic agent SLC5A2Glufosfamide antineoplastic agent SLC5A4 glyburide antidiabetic ABCC8 metformin antidiabetic PRKABl glycopyrrolate antineoplastic agent CHRM1GMI-1070 for treatment of sickle-cell disease SELEGMI-1070 for treatment of sickle-cell disease SELLGMI-1070 for treatment of sickle-cell disease SELPGMX1777 antineoplastic agent NAMPT BI-42902 for treatment of postmenopausal GNRHR symptoms,antineoplastic agentBI-42902 for treatment of postmenopausal GNRHR2 symptoms,antineoplastic agentGPI-1485 antiparkinson agent FKBP1AGPX-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 HTR3DDrug Name Indication(s) Gene granisetron antiemetic HTR3EGS-9411 for treatment of pulmonary disease SCNN1AGS-9411 for treatment of pulmonary disease SCNN1BGS-9411 for treatment of pulmonary disease SCNN1DGS-9411 for treatment of pulmonary disease SCNN1GGSI-136 for treatment of Alzheimer's disease APH1AGSI-136 for treatment of Alzheimer's disease APH1BGSI-136 for treatment of Alzheimer's disease NCSTNGSI-136 for treatment of Alzheimer's disease PSEN1GSI-136 for treatment of Alzheimer's disease PSEN2GSI-136 for treatment of Alzheimer's disease PSE ENGSK- 1004723 antiallergy agent HRH1GSK- 1004723 antiallergy agent HRH3 trametinib antineoplastic agent MAP2K1GSK2118436 antineoplastic agent BRAFGSK-961081 bronchodilator ADRB2GSK-961081 bronchodilator CHRM3GTS-21 for treatment of schizophrenia CHRNA7GTx-758 antineoplastic agent LHCGR guanfacine for treatment of ADHD ADRA2AGW501516 antidyslipidaemic agent PPARAGW501516 antidyslipidaemic agent PPARDGW501516 antidyslipidaemic agent PPARGGW642444 bronchodilator ADRB2 halofuginone antineoplastic agent EPRS flurbiprofen antiinflammatory agent,NSAID PTGS2 nitric oxide antiinflammatory agent GUCY1A2HE3235 antineoplastic agent ARDrug Name Indication(s) Gene doxorubicin antineoplastic agent TOP2A heparin anticoagulant F10 heparin anticoagulant SERPINC1 heparin anticoagulant F10 heparin anticoagulant SERPINC1HF0220 for treatment of alzheimer's disease unknownHGS1029 antineoplastic agent BIRC2HGS1029 antineoplastic agent BIRC3HGS1029 antineoplastic agent BIRC5HGS1029 antineoplastic agent XIAP amlodipine antihypertensive agent CACNA1C amlodipine antihypertensive agent CACNA1D amlodipine antihypertensive agent CACNA1 S 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 R3C2 huperzine-A for treatment of Alzheimer's disease ACHE hydralazine antihypertensive agent AOC3 isosorbide dinitrate antihypertensive agent NPR 1 hydroxytamoxifen for treatment of cyclic mastalgia ESR1 hydroxytamoxifen for treatment of cyclic mastalgia ESR2 famotidine acid reducer HRH2Drug Name Indication(s) Gene famotidine for treatment of gastric ulcer and HRH2 gastroesophageal refluxibuprofen NSAID PTGS1 ibuprofen NSAID PTGS2 ibandronate antiosteoporotic agent FDPS dexamethasone antiinflammatory R3C1 agent, glucocorticoid, for treatment ofMeniere's diseaseibudilast neuroprotectant PDE4A ibudilast neuroprotectant PDE4B ibudilast neuroprotectant PDE4CICA- 105665 anticonvulsant KCNQ1ICA- 105665 anticonvulsant KCNQ2ICA- 105665 anticonvulsant KCNQ3ICA- 105665 anticonvulsant KCNQ4ICA- 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 HTR6Drug Name Indication(s) Gene iloperidone antipsychotic agent, atypical HTR7 iloprost antihypertensive agent PTGER1 iloprost antihypertensive agent PTGIR fluocinolone acetonide antiinflammatory R3C1 agent, glucocorti coi dimatinib 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 RETImiquimod anti wart agent,antineoplastic agent TLR7 implitapide antiatherosclerotic agent MTTPINCB13739 antidiabetic HSD11B1INCB 18424 antineoplastic JAK1 agent,antiinflammatory agentINCB 18424 antineoplastic JAK2 agent,antiinflammatory agentINCB3284 antiinflammatory agent,DMARD CCR2INCB7839 antineoplastic agent ADAM 10INCB7839 antineoplastic agent ADAM 17 indacaterol bronchodilator ADRB2 indomethacin NSAID KC E1 indomethacin NSAID KCNQ1Indiplon hypnotic GABRA1 inecalcitol antineoplastic agent,prostate cancer VDRDrug Name Indication(s) Gene apomorphine for treatment of sexual dysfunction in DRD2 women,for treatment of erectiledysfunction,antiparkinson agentapomorphine for treatment of sexual dysfunction in DRD3 women,for treatment of erectiledysfunction,antiparkinson agentapomorphine for treatment of sexual dysfunction in DRD4 women,for treatment of erectiledysfunction,antiparkinson agentatropine 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 PARP 1INK128 antineoplastic agent CRTC1INK128 antineoplastic agent CRTC2INNO-206 antineoplastic agent TOP2AINO-8875 for treatment of glaucoma AD OR A 1INS37217 for treatment of rhegmatogenous P2RY2 retinal detachmentINS37217 for treatment of cystic fibrosis,for P2RY2 treatment of perennial allergicrhinitisINSM-18 antineoplastic agent,prostate cancer ERBB2INSM-18 antineoplastic agent,prostate cancer IGF1RAMG-131 antidiabetic PPARGDrug Name Indication(s) Gene apomorphine for treatment of sexual dysfunction in DRD2 women,for treatment of erectiledysfunction,antiparkinson agentapomorphine for treatment of sexual dysfunction in DRD3 women,for treatment of erectiledysfunction,antiparkinson agentapomorphine for treatment of sexual dysfunction in DRD4 women,for treatment of erectiledysfunction,antiparkinson agentketorolac NSAID PTGS2 morphine analgesic OPRD1 morphine analgesic OPRK1 morphine analgesic OPRM1 retaspimycin antineoplastic agent HSP90AA1 retaspimycin antineoplastic agent HSP90AA2 retaspimycin antineoplastic agent HSP90AB1IPI-504 antineoplastic agent HSP90AA1IPI-504 antineoplastic agent HSP90AA2IPI-504 antineoplastic agent HSP90AB1IPI-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 AGTR1Drug Name Indication(s) Gene gefitinib antineoplastic agent EGFR irinotecan antineoplastic agent TOPI isofagomine 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 PTGS2Givinostat antineoplastic HDAC1 agent,antiinflammatory agentGivinostat antineoplastic HDAC10 agent,antiinflammatory agentGivinostat antineoplastic HDAC2 agent,antiinflammatory agentGivinostat antineoplastic HDAC3 agent,antiinflammatory agentGivinostat antineoplastic HDAC4 agent,antiinflammatory agentGivinostat antineoplastic HDAC5 agent,antiinflammatory agentGivinostat antineoplastic HDAC6 agent,antiinflammatory agentGivinostat antineoplastic HDAC7 agent,antiinflammatory agentDrug Name Indication(s) GeneGivinostat antineoplastic HDAC8 agent,antiinflammatory agentGivinostat antineoplastic HDAC9 agent,antiinflammatory agentITI-007 antipsychotic agent DRD2ITI-007 antipsychotic agent HTR2AITI-007 antipsychotic agent PPP1R1BITI-007 antipsychotic agent SLC6A4 itopride motilitant ACHE itopride motilitant DRD2IW-6118 analgesic FAAH ixabepilone antineoplastic agent TUBB3JB991 antiinflammatory PPARG agent,dermatologic agentJNJ-37822681 antipsychotic agent DRD2JSM 6427 for treatment of age-related macular ITGA5 degenerationJSM 6427 for treatment of age-related macular ITGB1 degenerationropinirole for treatment of restlegs legs DRD2 syndromeropinirole for treatment of restlegs legs DRD3 syndromeropinirole for treatment of restlegs legs DRD4 syndromeclonazepam anticonvulsant GABRA2 clonazepam anticonvulsant GABRA3 clonazepam anticonvulsant GABRA5Drug Name Indication(s) Gene 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 GABRR2Karenitecin antineoplastic agent TOPIKC706 antiinflammatory agent,DMARD MAPK11KC706 antiinflammatory agent,DMARD MAPK12KC706 antiinflammatory agent,DMARD MAPK13KC706 antiinflammatory agent,DMARD MAPK14KD3010 antiobesity agent,for treatment of PPARD metabolic disordersketoprofen NSAID PTGS1 ketoprofen NSAID PTGS2 ketoprofen NSAID PTGS1 ketoprofen NSAID PTGS1 ketoprofen NSAID PTGS2 ketoprofen NSAID PTGS2Drug Name Indication(s) Gene ketorolac NSAID PTGS1 ketorolac NSAID PTGS2 ketotifen antiallergy agent HRH1 ketoprofen NSAID PTGS1 ketoprofen NSAID PTGS1 ketoprofen NSAID PTGS2 ketoprofen NSAID PTGS2KN38-7271 neuroprotectant CNR1KN38-7271 neuroprotectant CNR2KOS-2187 for treatment of gastrointestinal MLNR motility disorderskp201 analgesic OPRD1 kp201 analgesic OPRK1 kp201 analgesic OPRM1KRP-104 antidiabetic DPP4KUC-7483 for treatment of overactive bladder ADRB3KX2-391 antineoplastic agent SRC granisetron antiemetic HTR3ALacosamide anti convul sant, analgesi c, neuropathi c DPYSL2 painlamotrigine anticonvulsant SCN2A lanreotide for treatment of acromegaly SSTR1 lanreotide for treatment of acromegaly SSTR5 lansoprazole antiulcer agent ATP4A lansoprazole antiulcer agent ATP4ALAS- 100977 bronchodilator ADRB2 lasmiditan antimigraine agent HTR1FDrug Name Indication(s) Gene lasofoxifene antiosteoporotic agent,hormone ESR1 replacement therapylatanoprost for treatment of glaucoma PTGFR timolol for treatment of glaucoma ADRB 1 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 FRAP1Erismodegib antineoplastic agent SMOLEE011 antineoplastic agent CDK4LEE011 antineoplastic agent CDK6 lercanidipine antihypertensive agent CACNG1LE-SN38 antineoplastic agent TOPILE-SN38 antineoplastic agent TOP1MT lesogaberan for treatment of gastrointestinal GABBR1 reflux diseaselesogaberan for treatment of gastrointestinal GABBR2 reflux diseaselestaurtinib antineoplastic agent FLT3 lestaurtinib antineoplastic agent NTRK1 lestaurtinib antineoplastic agent NTRK2 lestaurtinib antineoplastic agent NTRK3 lestaurtinib antineoplastic agent JAK2Drug Name Indication(s) Gene 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 SRD5A1Levosimendan for treatment of heart failure KCNJ11Levosimendan for treatment of heart failure TNNC1 levothyroxine hormone replacement THRA levothyroxine hormone replacement THRB levothyroxine hormone replacement THRA levothyroxine hormone replacement THRBLGD-1550 antineoplastic agent RARALGD-1550 antineoplastic agent RARBLGD-1550 antineoplastic agent RARGLGD-2941 antiosteoporotic agent ARDrug Name Indication(s) GeneLGD-4033 hormone replacement ARLGD-4665 thrombopoietic agent MPLLiarozole dermatological agent,for treatment of CYP26A1 ichtyosislicarbazepine 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 SCN9ALIM-0705 for improving pharmacokinetics of ABCA5 tacrolimusLIM-0705 for improving pharmacokinetics of ABCBl tacrolimusLinaglipton antidiabetic DPP4 fluticasone propionate for treatment of symptomatic R3C1 exophthalmos associated withthyroid-related eye diseaseDrug Name Indication(s) Gene salbutamol for treatment of symptomatic ADRB2 exophthalmos associated withthyroid-related eye diseasedocetaxel antineoplastic agent BCL2 docetaxel antineoplastic agent TUBB1 doxorubicin antineoplastic agent TOP2A paclitaxel antineoplastic agent TOP2A lurtotecan antineoplastic agent TOPI mitoxantrone antineoplastic agent TOP2A prednisolone antiinflammatory R3C1 agent, corti costeroi dLipotecan antineoplastic agent TOPI lisinopril antihypertensive agent ACELisofylline antidiabetic STAT4 lixivaptan for treatment of hyponatremia AVPR2Lobeline for treatment of metamphetamine SLC18A2 addictonlofexidine for treatment of opiate withdrawal ADRA2A lofexidine for treatment of opiate withdrawal ADRA2B lofexidine for treatment of opiate withdrawal ADRA2C lomitapide anticholesterolaemic agent MTTPLOR-253 antineoplastic agent MTF1 loratadine antiasthmatic agent HRH1 montelukast antiasthmatic agent CYSLTR1Lorcaserin antiobesity agent HTR2C loteprednol etabonate antiinflammatory R3C1 agent, corti costeroi dmethamphetamine neuroprotectant ADRA2ADrug Name Indication(s) Gene 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 SLC6A4Tedatioxetine antidepressant ADRA1ATedatioxetine antidepressant HTR2CTedatioxetine antidepressant HTR2CTedatioxetine antidepressant HTR3ATedatioxetine antidepressant SLC6A2Tedatioxetine antidepressant SLC6A3Tedatioxetine antidepressant SLC6A4 zicronapine antipsychotic agent DRD4Lu-AE58054 antipsychotic agent HTR6Lubiprostone motilitant,for treatment of irritable CLCN2 bowel disorderDrug Name Indication(s) Gene 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 HTR7LX1031 for treatment of irritable bowel TPH1 syndromeLX1032 for treatment of carcinoid syndrome TPH1 cyclosporine A immunosuppressant, opthalmological CAMLG agentcyclosporine A immunosuppressant, opthalmological PPP3R2 agentLX4211 antidiabetic SLC5A1LX4211 antidiabetic SLC5A2LY2140023 antipsychotic agent GRM2LY2140023 antipsychotic agent GRM3LY3009104 antiinflammatory agent,DMARD JAK1LY3009104 antiinflammatory agent,DMARD JAK2 semagacestat for treatment of Alzheimer's disease PSEN1 semagacestat for treatment of Alzheimer's disease PSEN2LY-517717 anticoagulant F10 naveglitazar antidiabetic PPARADrug Name Indication(s) Gene naveglitazar antidiabetic PPARGLY-674 anticholesterolaemic agent PPARAM0002 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 R3C1 agent, glucocorti coi dformoterol bronchodilator ADRB2 budesonide antiinflammatory R3C1 agent, glucocorti coi dmasitinib antiinflammatory ABL1 agent,DMARD,antineoplastic agentmasitinib antiinflammatory CSF1R agent,DMARD,antineoplastic agentmasitinib antiinflammatory HCKagent,DMARD,antineoplastic agentmasitinib antiinflammatory KITagent,DMARD,antineoplastic agentmasitinib antiinflammatory LYNagent,DMARD,antineoplastic agentDrug Name Indication(s) Gene masitinib antiinflammatory PDGFRA agent,DMARD,antineoplastic agentmasitinib antiinflammatory PDGFRB agent,DMARD,antineoplastic agentmasitinib antiinflammatory SRC agent,DMARD,antineoplastic agentmesalazine 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 PTGS2MB07811 antidyslipidaemic agent THRBMBX-2044 antidiabetic PPARGMBX-2982 antidiabetic GPR119MBX-8025 antidyslipidaemic agent PPARD lisinopril antihypertensive agent ACE lisinopril antihypertensive agent ACE2MC-1 cardioprotectant LPAR4MC-1 cardioprotectant LPAR6MC-1 cardioprotectant P2RY1MC-1 cardioprotectant P2RY10MC-1 cardioprotectant P2RY11MC-1 cardioprotectant P2RY12MC-1 cardioprotectant P2RY13MC-1 cardioprotectant P2RY14MC-1 cardioprotectant P2RY2MC-1 cardioprotectant P2RY4MC-1 cardioprotectant P2RY6MC-1 cardioprotectant P2RY8Drug Name Indication(s) GeneMCD-386 for treatment of Alzheimer's disease CHRM1MDAM antineoplastic agent DHFRMDV3100 antineoplastic agent ARMebendazole antineoplastic agent TUBA1AMebendazole antineoplastic agent TUBB2C mecamylamine for treatment of ADHD CHRNA2 melogliptin antidiabetic DPP4MEM 1003 for treatment of Alzheimer's disease CACNA1CMEM 1003 for treatment of Alzheimer's disease CACNA1DMEM 1003 for treatment of Alzheimer's disease CACNA1FMEM 1003 for treatment of Alzheimer's disease CACNA1 SMEM 1414 for treatment of Alzheimer's disease PDE4AMEM 1414 for treatment of Alzheimer's disease PDE4BMEM 63908 for treatment of Alzheimer's disease CHRNA7MEM3454 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 mesal amine antiinflammatory agent ALOX5 mesal amine antiinflammatory agent PPARG mesal amine antiinflammatory agent PTGS1 mesal amine antiinflammatory agent PTGS2WX-671 antineoplastic agent PLAUDrug Name Indication(s) GeneOxypurinol for treatment of heart failure,for XDH treatment of goutmetaglidasen antidiabetic PPARG metformin antidiabetic PRKAB1 metformin antidiabetic PRKAB1 metformin antidiabetic PRKAB1Methylnaltrexone for treatment of opioid-induced OPRM1 constipationmethylphenidate 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 ARin womenmetoclopramide motilitant,for treatment of CHRM1 gastroesophageal reflux diseasemetoclopramide motilitant,for treatment of DRD2 gastroesophageal reflux diseasemetoclopramide antiemetic CHRM1 metoclopramide antiemetic DRD2 metoprolol antihypertensive agent ADRB1MF101 for treatment of menopausal ESR2 symptomsDrug Name Indication(s) GeneMGCD-0103 antineoplastic agent HDAC1MGCD-0103 antineoplastic agent HDAC10MGCD-0103 antineoplastic agent HDAC11MGCD-0103 antineoplastic agent HDAC2MGCD-0103 antineoplastic agent HDAC3MGCD-0103 antineoplastic agent HDAC4MGCD-0103 antineoplastic agent HDAC5MGCD-0103 antineoplastic agent HDAC6MGCD-0103 antineoplastic agent HDAC7AMGCD-0103 antineoplastic agent HDAC8MGCD-0103 antineoplastic agent HDAC9MGCD265 antineoplastic agent FLT1MGCD265 antineoplastic agent FLT4MGCD265 antineoplastic agent KDRMGCD265 antineoplastic agent METMGCD265 antineoplastic agent MST1RMGCD265 antineoplastic agent TEK morphine analgesic OPRD1 morphine analgesic OPRK1 morphine analgesic OPRM1 paclitaxel antiinflammatory agent,DMARD BCL2 paclitaxel antiinflammatory agent,DMARD TUBB1Midostaurin antineoplastic agent FLT3Mifepristone opthalmological agent,for lowering R3C1 intraocular pressureMifepristone opthalmological agent,for lowering PGR intraocular pressureMifepristone antip sy choti c, anti depres sant R3C1Drug Name Indication(s) GeneMifepristone antip sy choti c, anti depres sant PGR migalastat enzyme replacement therapy,for GLA treatment of Fabry diseasemiglustat for treatment of Gaucher' s disease UGCG milataxel antineoplastic agent BCL2 milataxel antineoplastic agent TUBB1Milnacipran for treatment of fibromyalgia SLC6A2 syndromeMilnacipran for treatment of fibromyalgia SLC6A4 syndromemilveterol bronchodilator ADRB2MIM-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 ML R mitiglinide antidiabetic ABCC8 mitoxantrone antineoplastic agent TOP2AMIV-701 for treatment of osteoporosis CTSK laropiprant for counteracting niacin-induced PTGDR flushingniacin antidyslipidaemic agent GPR109A niacin antidyslipidaemic agent GPR109B niacin antidyslipidaemic agent NNMTDrug Name Indication(s) Gene niacin antidyslipidaemic agent QPRT laropiprant for counteracting niacin-induced PTGDR flushingniacin antidyslipidaemic agent GPR109A niacin antidyslipidaemic agent GPR109B niacin antidyslipidaemic agent NNMT niacin antidyslipidaemic agent QPRT simvastatin anticholesterolaemic agent HMGCRMK-1775 antineoplastic agent WEE1MK-2206 antineoplastic agent AKT1MK-2206 antineoplastic agent AKT2MK-2206 antineoplastic agent AKT3 suvorexant hypnotic HCRTR1 suvorexant hypnotic HCRTR2MK-4827 antineoplastic agent PARP1MK-4827 antineoplastic agent PARP2MKC-1 antineoplastic agent IPOl lMKC-1 antineoplastic agent IP013MKC-1 antineoplastic agent IP04MKC-1 antineoplastic agent IP07MKC-1 antineoplastic agent IP08MKC-1 antineoplastic agent IP09MKC-1 antineoplastic agent TUBBMKC-1 antineoplastic agent TUBB1MLN-0415 antiinflammatory agent IKBKBMLN-4924 antineoplastic agent UBA3MLN-8054 antineoplastic agent AUR2MLN-8237 antineoplastic agent AURKADrug Name Indication(s) GeneMLN-9708 antineoplastic agent PSMB1MLN-9708 antineoplastic agent PSMB2MLN-9708 antineoplastic agent PSMB5MLN-9708 antineoplastic agent PSMD1MLN-9708 antineoplastic agent PSMD2MN-201 antineoplastic agent VDRMN-246 for treatment of overactive bladder ADRB3MN-305 anti depres sant, hypnoti c HTR1A moclobemide antidepressant MAOA modafinil central nervous system stimulant SLC6A3Modufolin antineoplastic agent TYMS formoterol antiasthmatic agent ADRB2 mometasone antiinflammatory NR3C1 agent, glucocorti coi dmontelukast 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 OPRK1Drug Name Indication(s) Gene 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 CXCR4MP0112 for treatment of diabetic retinopathy FLT1MP0112 for treatment of diabetic retinopathy KDRDrug Name Indication(s) Gene 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 RETMPC-0920 antithrombotic F2MPI-674 for treatment of abnormal uterine CYP19A1 bleeding (AUB)MPI-676 for treatment of endometriosis CYP19A1 nitroglycerin for treatment of Raynaud's disease NPR 1MRX-4 antiinflammatory agent PLA2G3MRX-6 antiinflammatory agent PLA2G3 mitoglitazone antidiabetic PPARG talniflumate for treatment of cystic fibrosis CLCA1MSX-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 HTR1DDrug Name Indication(s) Gene sumatriptan antimigraine agent HTR1F doxorubicin antineoplastic agent TOP2A isothiourea antihypertensive agent NOS1 isothiourea antihypertensive agent NOS2 isothiourea antihypertensive agent NO S3 muraglitazar antidiabetic PPARA muraglitazar antidiabetic PPARG mycophenolic acid immunosuppressant IMPDH1 mycophenolic acid immunosuppressant IMPDH2MPC-3100 antineoplastic agent HSP90AA1MPC-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 addictionnalmefene smoking-cessation agent,for OPRK1 treatment of addictionnalmefene smoking-cessation agent,for OPRM1 treatment of addictionmemantine 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 PTGS1Drug Name Indication(s) Gene diclofenac NSAID PTGS2Naproxcinod NSAID GUCY1A2Naproxcinod NSAID PTGS1Naproxcinod 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 GRIN3ANav 1.7 blocker analgesic SCN9ANB-1011 antineoplastic agent TYMSNBI-56418 antineoplastic agent GNRHRNBI-98854 antipsychotic agent SLC18A2NCX 1510 antiallergy agent GUCY1A2NCX 1510 antiallergy agent HRH1NCX 4016 antithrombotic GUCY1A2NCX 4016 antithrombotic PTGS1NCX 4016 antithrombotic PTGS2 carbidopa antiparkinson agent DDC nebivolol antihypertensive agent ADRBl nelarabine antineoplastic agent POLA1Drug Name Indication(s) Gene nepicastat for treatment of addiction,for DBH treatment of post-traumatic stress disorderneramexane 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 PGRNeu-2000 cardioprotectant GRIN1Neu-2000 cardioprotectant GRIN2ANeu-2000 cardioprotectant GRIN2BNeu-2000 cardioprotectant GRIN2CNeu-2000 cardioprotectant GRIN2DNeu-2000 cardioprotectant GRIN3ANeu-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 RAFlNG2-73 hypnotic GABRA2Drug Name Indication(s) GeneNG2-73 hypnotic GABRA3NG2-73 hypnotic GABRA5NG2-73 hypnotic GABRA6NG2-73 hypnotic GABRB1NG2-73 hypnotic GABRB1NG2-73 hypnotic GABRB2NG2-73 hypnotic GABRB2NG2-73 hypnotic GABRB3NG2-73 hypnotic GABRDNG2-73 hypnotic GABRDNG2-73 hypnotic GABRENG2-73 hypnotic GABRG1NG2-73 hypnotic GABRG2NG2-73 hypnotic GABRG3NG2-73 hypnotic GABRG3NG2-73 hypnotic GABRPNG2-73 hypnotic GABRQNG2-73 hypnotic GABRR2NGD-4715 appetite suppressant MCHR1NGD-8243 analgesic TRPV1NGX267 for treatment of dry mouth CHRM1 niacin receptor agonist antiatherosclerotic agent HCAR2 niacin receptor agonist antiatherosclerotic agent HCAR3NIC5-15 for treatment of Alzheimer's disease APH1ANIC5-15 for treatment of Alzheimer's disease PSE EN nilotinib antineoplastic agent ABLlDrug Name Indication(s) Gene nitisinone for treatment of restlegs legs HPD syndrome,for treatment of hereditary tyrosinemia type 1 (HT-1)PEG-irinotecan antineoplastic agent TOPIPEG-irinotecan antineoplastic agent TOP1MTPEG-docetaxel antineoplastic agent BCL2PEG-docetaxel antineoplastic agent TUBB1PEG-naloxol for treatment of opioid-induced OPRM1 constipationM-702 for treatment of intermittent PDE3A claudicationM-702 for treatment of intermittent PDE3B claudicationhydromorphone analgesic OPRD1 hydromorphone analgesic OPRK1 hydromorphone analgesic OPRM1 MS-1116354 antineoplastic agent CDC7 NZ-2566 neuroprotectant IGF1 ethinyl estradiol contraceptive ESR1 norelgestromin contraceptive ESR1 norelgestromin contraceptive PGR noscapine antineoplastic agent HIF1A latanoprost for treatment of glaucoma PTGFRCyclosporine A immunosuppressant, opthalmological CAMLG agentCyclosporine A immunosuppressant, opthalmological PPP3R2 agentsumatriptan antimigraine agent HTR1ADrug Name Indication(s) Gene sumatriptan antimigraine agent HTR1B sumatriptan antimigraine agent HTR1D sumatriptan antimigraine agent HTR1F17-beta estradiol opthalmological agent ESR117-beta estradiol opthalmological agent ESR2Fluoxetine for treatment of autism HTR2AFluoxetine for treatment of autism SLC6A4 PS-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 RM8499 for treatment of Alzheimer's disease APP RP290 analgesic OPRD1 RP290 analgesic OPRK1Drug Name Indication(s) Gene RP290 analgesic OPRM1 triiodothyronine (T3) hormone replacement THRA triiodothyronine (T3) hormone replacement THRB RX-5183 hematopoietic agent RARANS-304 antihypertensive agent PTGIRNSD-644 analgesic,antidepressant SLC6A2NSD-644 analgesic,antidepressant SLC6A3NSD-644 analgesic,antidepressant SLC6A4NSD-788 antidepressant SLC6A2NSD-788 antidepressant SLC6A4 allopurinol for treatment of gout XDHNV-52 antiinflammatory agent TBXAS1 glycopyrronium for treatment of chronic obstructive CHRM1 pulmonary disease (COPD)tizanidine for treatment of skeletal muscular ADRA2A spasticitytizanidine for treatment of skeletal muscular ADRA2B spasticitytizanidine for treatment of skeletal muscular ADRA2C spasticityNXN-188 antimigraine agent HTR1BNXN-188 antimigraine agent HTR1DNXN-188 antimigraine agent NOS1 ondansetron antiemetic HTR3A paclitaxel antineoplastic agent BCL2 paclitaxel antineoplastic agent TUBB1 obatoclax antineoplastic agent BCL2 betahistine antiobesity agent HRH1Drug Name Indication(s) Gene betahistine antiobesity agent HRH3 obeticholic acid for treatment of non-alcoholic fatty R1H4 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 CTSKOglemilast antiasthmatic agent PDE4ADrug Name Indication(s) GeneOglemilast antiasthmatic agent PDE4B olanzapine antipsychotic agent ADRA 1 A olanzapine antipsychotic agent ADRA 1 B 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 disorderDrug Name Indication(s) Gene olanzapine antidepressant,for treatment of ADRA 1 A bipolar disorderolanzapine antidepressant,for treatment of ADRA 1 B bipolar disorderolanzapine antidepressant,for treatment of ADRA2A bipolar disorderolanzapine antidepressant,for treatment of ADRA2B bipolar disorderolanzapine antidepressant,for treatment of ADRA2C bipolar disorderolanzapine antidepressant,for treatment of CHRM1 bipolar disorderolanzapine antidepressant,for treatment of CHRM2 bipolar disorderolanzapine antidepressant,for treatment of CHRM3 bipolar disorderolanzapine antidepressant,for treatment of CHRM4 bipolar disorderolanzapine antidepressant,for treatment of CHRM5 bipolar disorderolanzapine antidepressant,for treatment of DRD1 bipolar disorderolanzapine antidepressant,for treatment of DRD2 bipolar disorderolanzapine antidepressant,for treatment of DRD3 bipolar disorderolanzapine antidepressant,for treatment of DRD4 bipolar disorderDrug Name Indication(s) Gene olanzapine antidepressant,for treatment of DRD5 bipolar disorderolanzapine antidepressant,for treatment of HRH1 bipolar disorderolanzapine antidepressant,for treatment of HTR1A bipolar disorderolanzapine antidepressant,for treatment of HTR1B bipolar disorderolanzapine antidepressant,for treatment of HTR1D bipolar disorderolanzapine antidepressant,for treatment of HTR1E bipolar disorderolanzapine antidepressant,for treatment of HTR2A bipolar disorderolanzapine antidepressant,for treatment of HTR2C bipolar disorderolanzapine antidepressant,for treatment of HTR3A bipolar disorderolanzapine antidepressant,for treatment of HTR6 bipolar disorderolanzapine antidepressant,for treatment of HTR7 bipolar disorderolesoxime 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 AGTR1Drug Name Indication(s) Geneolopatadine 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 GAPDAamyotrophic lateral sclerosis (ALS)omigapil antiparkinson agent,for treatment of SIAH1amyotrophic 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 ADRAIA oxymetazoline analgesic ADRAIA oxymetazoline analgesic ADRA2A oxymetazoline analgesic ADRA2A rigosertib antineoplastic agent PIK3CA rigosertib antineoplastic agent PIK3CB rigosertib antineoplastic agent PIK3CDDrug Name Indication(s) Gene rigosertib antineoplastic agent PLK1 paclitaxel antineoplastic agent BCL2 paclitaxel 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 paclitaxel antineoplastic agent BCL2 paclitaxel antineoplastic agent TUBB1OPB-51602 antineoplastic agent STAT3OPC-28326 vasodilator ADRA2BOPC-28326 vasodilator ADRA2COPC-34712 antidepressant DRD2OPC-34712 antidepressant HTR1AOPC-34712 antidepressant HTR2AOPC-34712 antidepressant HTR7OPC-51803 for treatment of incontinence AVPR2 doxycyklin for treatment of dental disease MMP8 estrogen contraceptive,for treatment of female ESR1 sexual dysfunctionestrogen contraceptive,for treatment of female ESR2 sexual dysfunctionprogestogen contraceptive,for treatment of female PGR sexual dysfunctionestriol E3 for treatment of multiple sclerosis ESR1 estriol E3 for treatment of multiple sclerosis ESR2Drug Name Indication(s) Gene paclitaxel antineoplastic agent BCL2 paclitaxel 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 HTR2CDrug Name Indication(s) Gene 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 CYP17A1OSI-027 antineoplastic agent MTOROSI-461 antineoplastic agent PDE5AOSI-7904L antineoplastic agent TYMSOSI-906 antineoplastic agent IGF1ROSI-930 antineoplastic agent KDRDrug Name Indication(s) Gene ospemifene for treatment of postmenopausal ESR1 vaginal atrophyospemifene for treatment of postmenopausal ESR2 vaginal atrophyenobosarm hormone replacement AROT-730 for treatment of glaucoma ADRB 1OT-730 for treatment of glaucoma ADRB2 otamixaban antithrombotic F10 dexamethasone antiinflammatory R3C1 agent, glucocorticoid, for treatment ofMeniere's diseasefamotidine acid reducer HRH2 omeprazole Proton pump inhibitor ATP4AZolpidem hypnotic GABRA1Zolpidem hypnotic GABRA2Zolpidem hypnotic GABRA30X914 antiallergy agent PDE4A0X914 antiallergy agent PDE4B oxandrolone anabolic agent AR oxcarbazepine anticonvulsant SCN5A combretastatin Al 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 QPRTDrug Name Indication(s) Gene oxycodone analgesic OPRD1 oxycodone analgesic OPRK1 oxycodone analgesic OPRM1 oxycodone analgesic OPRD1 oxycodone analgesic OPRK1 oxycodone analgesic OPRM1 oxymorphone analgesic OPRD1 oxymorphone analgesic OPRM1P-552 for treatment of dry mouth ACCN2P-552 for treatment of dry mouth ACCN3P-552 for treatment of dry mouth ACCN4P-552 for treatment of dry mouth ASIC2P-552 for treatment of dry mouth SCNN1AP-552 for treatment of dry mouth SCNN1BP-552 for treatment of dry mouth SCNN1DP-552 for treatment of dry mouth SCNN1G acetylsalicylic acid NSAID PTGS1 acetylsalicylic acid NSAID PTGS2 omeprazole Proton pump inhibitor ATP4A paclitaxel antineoplastic agent BCL2 paclitaxel antineoplastic agent TUBB1 paclitaxel antineoplastic agent BCL2 paclitaxel antineoplastic agent TUBB1 paclitaxel for treatment of peripheral arterial BCL2 disease (PAD)paclitaxel for treatment of peripheral arterial TUBB1 disease (PAD)Drug Name Indication(s) Gene pagoclone for treatment of premature GABRA2 ejaculation,for treatment of persistant stutteringpagoclone for treatment of premature GABRB2 ejaculation,for treatment of persistant stutteringpaliperidone antipsychotic agent DRD2 paliperidone antipsychotic agent HTR2APalomid 529 for treatment of age-related macular MTOR degenerationPalonosetron antiemetic HTR3APanobinostat antineoplastic agent HDAC1Panobinostat antineoplastic agent HDAC10Panobinostat antineoplastic agent HDAC11Panobinostat antineoplastic agent HDAC2Panobinostat antineoplastic agent HDAC3Panobinostat antineoplastic agent HDAC4Panobinostat antineoplastic agent HDAC5Panobinostat antineoplastic agent HDAC6Panobinostat antineoplastic agent HDAC7APanobinostat antineoplastic agent HDAC8Panobinostat 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 DRD4Drug Name Indication(s) Gene pardoprunox antiparkinson agent HTR1A pardoprunox antiparkinson agent HTR7 parecoxib antiinflammatory agent,NSAID PTGS2 paricalcitol for treatment of hype arathyroidism VDR paroxetine antidepressant SLC6A4Pazopanib antineoplastic agent FLT1Pazopanib antineoplastic agent FLT4Pazopanib antineoplastic agent KDR bleomycin antineoplastic agent LIG1CRA-024781 antineoplastic agent HDAC1CRA-024781 antineoplastic agent HDAC10CRA-024781 antineoplastic agent HDAC2CRA-024781 antineoplastic agent HDAC3CRA-024781 antineoplastic agent HDAC6 ibrutinib antineoplastic agent BTKPD-6735 hypnotic MTNR1APD-6735 hypnotic MTNR1B10-propargyl-lO- antineoplastic agent DHFR deazaaminopterinPEG-camptothecin antineoplastic agent TOPI pentosan polysulfate for symptomatic treatment of bladder FGF1 pain or discomfort associated with interstitial cystitispentosan polysulfate for symptomatic treatment of bladder FGF2 pain or discomfort associated with interstitial cystitisDrug Name Indication(s) Gene pentosan polysulfate for symptomatic treatment of bladder FGF4 pain or discomfort associated withinterstitial cystitispentostatin antineoplastic agent ADA pentoxifylline for treatment of amyotrophic lateral AD OR A 1 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 agentingenol Mebutate for treatment of actinic PKN2 keratosis,antineoplastic agentingenol Mebutate for treatment of actinic PRKCA keratosis,antineoplastic agentingenol Mebutate for treatment of actinic PRKCB1 keratosis,antineoplastic agentingenol Mebutate for treatment of actinic PRKCD keratosis,antineoplastic agentingenol Mebutate for treatment of actinic PRKCE keratosis,antineoplastic agentingenol Mebutate for treatment of actinic PRKCG keratosis,antineoplastic agentDrug Name Indication(s) Gene ingenol Mebutate for treatment of actinic PRKCH keratosis,antineoplastic agentingenol Mebutate for treatment of actinic PRKCI keratosis,antineoplastic agentingenol Mebutate for treatment of actinic PRKCQ keratosis,antineoplastic agentingenol Mebutate for treatment of actinic PRKCZ keratosis,antineoplastic agentirinotecan antineoplastic agent TOPI irinotecan antineoplastic agent TOP1MT perifosine antineoplastic agent AKT1 perifosine antineoplastic agent AKT2 perifosine antineoplastic agent AKT3PF-00610355 bronchodilator ADRB2PF-04554878 antineoplastic agent PTK2Dacomitinib antineoplastic agent EGFRDacomitinib antineoplastic agent ERBB2Dacomitinib antineoplastic agent ERBB4PG-490-88 antineoplastic agent FKB1PG-490-88 antineoplastic agent FKB2PG545 antineoplastic agent HPSEPH-797804 antiinflammatory agent,DMARD MAPKl lPH-797804 antiinflammatory agent,DMARD MAPK12PH-797804 antiinflammatory agent,DMARD MAPK13PH-797804 antiinflammatory agent,DMARD MAPK14 phenoxodiol antineoplastic agent SPHK1 phenoxodiol antineoplastic agent SPHK2 phenserine for treatment of Alzheimer's disease ACHEDrug Name Indication(s) Gene physostigmine for treatment of dry mouth ACHEPimavanserin antiparkinson agent HTR2A pimecrolimus antiinflammatory agent MTOR pioglitazone antidiabetic PPARG metformin antidiabetic PRKABl pioglitazone antidiabetic PPARG pirfenidone for treatment of fibrotic conditions MAPKl l pirfenidone for treatment of fibrotic conditions MAPK12 pirfenidone for treatment of fibrotic conditions MAPK13 pirfenidone for treatment of fibrotic conditions MAPK14 pitavastatin anticholesterolaemic agent HMGCRPL37 analgesic,neuropathic pain ANPEPPL37 analgesic,neuropathic pain MME clopidogrel antithrombotic P2RY12PLK-1 inhibitor antineoplastic agent PLK1 vemurafenib antineoplastic agent BRAFPMI-001 antiinflammatory agent,DMARD R3C1 naproxen NSAID PTGS1 naproxen NSAID PTGS2 omeprazole Proton pump inhibitor ATP4A carmustine antineoplastic agent GSR ponatinib antineoplastic agent ABLl ponatinib antineoplastic agent SRC ponesimod antiinflammatory agent,for treatment S1PR1 of multiple sclerosisPosiphen for treatment of Alzheimer's disease APPPosiphen for treatment of Alzheimer's disease BACE1Posiphen for treatment of Alzheimer's disease BACE2Drug Name Indication(s) Gene pozanicline for treatment of Alzheimer's disease CHRNA4 pozanicline for treatment of Alzheimer's disease CHRNB2PPC-5650 analgesic ACCN2PPI-2458 antineoplastic agent METAP2PR- 15 antithrombotic GP6 prasterone hormone supplement for increasing ARbone mineral density in patients withsystemic lupus erythematosusprasugrel antithrombotic P2RY12 fenofibrate anticholesterolaemic agent PPARA pravastatin anticholesterolaemic agent HMGCR prednisolone antiinflammatory R3C1 agent, corti costeroi dprednisolone antiinflammatory R3C1 agent, corti costeroi dpregabalin analgesic,neuropathic pain,for CACNA1A treatment of restlegs legs syndromepreladenant antiparkinson agent ADORA2A pridopidine for treatment of Huntington's disease DRD2 desvenlafaxine for treatment of menopausal SLC6A2 symptoms,antidepressantdesvenlafaxine for treatment of menopausal SLC6A4 symptoms,antidepressantdiclofenac NSAID PTGS1 diclofenac NSAID PTGS2 telapri stone for treatment of uterin fibroids and PGRendometriosisDrug Name Indication(s) Gene progesterone for reducing the risk of pre-term birth PGRfor women with short cervix a mid- pregnancytestosterone hormone replacement AR eltrombopag thrombopoietic MPL propafenone antiarrythmic agent KC H2 propafenone antiarrythmic agent SCN5A propionyl-L-carnitine for treatment of intermittent CPT1A claudicationpropionyl-L-carnitine for treatment of intermittent CPT2 claudicationpropionyl-L-carnitine for treatment of intermittent CRAT claudicationpropionyl-L-carnitine for treatment of intermittent CROT claudicationpropionyl-L-carnitine for treatment of intermittent SLC22A4 claudicationpropionyl-L-carnitine for treatment of intermittent SLC22A5 claudicationpropionyl-L-carnitine for treatment of intermittent SLC25A20 claudicationpropionyl-L-carnitine for treatment of intermittent SLC25A29 claudicationpropofol sedative GABRB2 propofol sedative GABRB3 propofol sedative SCN2A propofol sedative SCN4A propofol sedative GABRB2Drug Name Indication(s) Gene propofol sedative GABRB3 propofol sedative SCN2A propofol sedative SCN4AOPC-14523 antidepressant HTR1AOPC-14523 antidepressant PGRMC1OPC-14523 antidepressant SIGMARlOPC-14523 antidepressant SLC6A4PRT062607 antiinflammatory agent SYK prucalopride motilitant HTR4PRX-00023 anti depres sant, anxi olyti c HTR1APRX-07034 antiobesity agent, nootropic HTR6PRX-08066 antihypertensive agent HTR2BPRX-3140 for treatment of Alzheimer's disease HTR4PS433540 antihypertensive agent AGTR1PS433540 antihypertensive agent AGTR2PS433540 antihypertensive agent ED RA lidocaine for treatment of premature EGFR ejaculationlidocaine for treatment of premature SCN10A ejaculationlidocaine for treatment of premature SCN5A ejaculationprilocaine for treatment of premature SCN5A ejaculationphenylephrine for treatment of incontinence ADRA1A phenylephrine for treatment of incontinence ADRA1B phenylephrine for treatment of incontinence ADRA1DPSD-506 for treatment of overactive bladder CHRM2Drug Name Indication(s) GenePSD-506 for treatment of overactive bladder CHRM3PSN357 antidiabetic PYGBPSN357 antidiabetic PYGLPSN357 antidiabetic PYGMPSN602 antiobesity agent HTR1APSN602 antiobesity agent SLC6A2PSN602 antiobesity agent SLC6A3PSN602 antiobesity agent SLC6A4PSN821 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 FLT1PTC299 antineoplastic agent FLT4PTC299 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 HTR2CDrug Name Indication(s) Gene 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 OPRK1Drug Name Indication(s) Gene oxycodone analgesic OPRM1 naltrexone analgesic OPRD1 naltrexone analgesic OPRK1 naltrexone analgesic OPRM1Pumosetrag motilitant HTR3APumosetrag motilitant HTR3BPumosetrag motilitant HTR3CPumosetrag motilitant HTR3DPumosetrag motilitant HTR3EPW2101 antihypertensive agent ADRB2PX-12 antineoplastic agent TXNPX-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 HDAC9PYM50028 antiparkinson agent GFRA1PYM50028 antiparkinson agent NGFRPYM50028 antiparkinson agent NTRK1PYM50028 antiparkinson agent NTRK2 quinapril antihypertensive agent ACEDrug Name Indication(s) Gene glycopyrronium bromide for treatment of chronic obstructive ADRB2 pulmonary disorder (COPD)indacaterol for treatment of chronic obstructive CHRMl pulmonary disorder (COPD)R112 antiallergy agent FCER1AR112 antiallergy agent FCER1GR112 antiallergy agent MS4A2R343 antiallergy agent SYKR348 antiinflammatory agent JAK3R667 for treatment of emphysema RARAR667 for treatment of emphysema RARBR667 for treatment of emphysema RARGR763 antineoplastic agent AURKAR763 antineoplastic agent AURKBR763 antineoplastic agent AURKCRAD1901 for treatment of postmenopausal ESR1 symptomsraltitrexed 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 MAOBRC-8800 for improving the antiproliferative CYP46A1 and apoptotic properties of vitaminD3Drug Name Indication(s) GeneRDEA119 antineoplastic agent MAPK1RDEA119 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 OPRM1Nalbuphine analgesic OPRD1Nalbuphine analgesic OPRK1Nalbuphine analgesic OPRM1 naloxone analgesic OPRD1 naloxone analgesic OPRK1 naloxone analgesic OPRM1 renzapride for treatment of irritable bowel HTR2A syndromerenzapride for treatment of irritable bowel HTR2B syndromerenzapride for treatment of irritable bowel HTR2C syndromerenzapride for treatment of irritable bowel HTR3A syndromerenzapride for treatment of irritable bowel HTR4 syndromerepaglinide antidiabetic ABCC8 ropinirol antiparkinson agent DRD2 ropinirol antiparkinson agent DRD3Drug Name Indication(s) Gene resiniferatoxin for treatment of interstitial TRPV1 cystitis,antiincontinence agentResminostat antineoplastic agent HDAC1Resminostat antineoplastic agent HDAC10Resminostat antineoplastic agent HDAC11Resminostat antineoplastic agent HDAC2Resminostat antineoplastic agent HDAC3Resminostat antineoplastic agent HDAC4Resminostat antineoplastic agent HDAC5Resminostat antineoplastic agent HDAC6Resminostat antineoplastic agent HDAC7AResminostat antineoplastic agent HDAC8Resminostat antineoplastic agent HDAC9Resveratrol for treatment of herpes simplex virus PDE4B1Resveratrol for treatment of herpes simplex virus PDE4D1retigabine anticonvulsant KCNQ1 retigabine anticonvulsant KCNQ2 retigabine anticonvulsant KCNQ3 retigabine anticonvulsant KCNQ4 retigabine anticonvulsant KCNQ5 rEV131 antiallergy agent HRH4 lenalidomide antineoplastic agent T FSF11RG2833 for treatment of Friedrich's ataxia HDAC3RG3039 for treatment of spinal muscular DCPS atrophyRidaforolimus antineoplastic agent MTORDrug Name Indication(s) Gene riluzole for treatment of ALS SCN5A riluzole for treatment of ALS SLC7A11 rimcazole antineoplastic agent SIGMAR1Rimonabant antiobesity agent C R1 riociguat antihypertensive agent GUCY1A2 riociguat antihypertensive agent GUCY1A3 riociguat antihypertensive agent GUCY1B2 riociguat antihypertensive agent GUCY1B3 risedronate antiosteoporotic agent FDPSRisperdal antipsychotic agent DRD2Risperdal antipsychotic agent HTR2A rivaroxaban antithrombotic F10 rivastigmine for treatment of Alzheimer's disease ACHE rivastigmine for treatment of Alzheimer's disease BCHERob 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 AD OR A 1 failureronacaleret antiiosteoporotic agent CASR ropivacaine anestethic SCN10A glimepiride antidiabetic ABCC8Drug Name Indication(s) Gene glimepiride antidiabetic KCNJ1 glimepiride antidiabetic KCNJ11 rosiglitazone antidiabetic PPARG metformin antidiabetic PRKABl rosiglitazone antidiabetic PPARG rosiglitazone for treatment of Alzheimer's PPARG di sease, anti di ab eti cketorolac antimigraine agent PTGS1 ketorolac antimigraine agent PTGS2 bromovinyl deoxyuridine antineoplastic agent POLA1RPC1063 for treatment of multiple sclerosis S1PR1RPL-554 bronchodilator PDE3ARPL-554 bronchodilator PDE3BRPL-554 bronchodilator PDE4ARPL-554 bronchodilator PDE4BRTA 744 antineoplastic agent TOP2ARTA 744 antineoplastic agent TOP2B rubitecan antineoplastic agent TOPI ruboxistaurin for treatment of diabetic neuropathy PRKCB1RVX-208 antiatherosclerotic agent APOA1 gimestat antineoplastic agent DPYD tegafur antineoplastic agent TYMS paclitaxel antineoplastic agent BCL2 paclitaxel antineoplastic agent TUBB1SA4503 anti depres sant, neuroprotectant SIGMAR1Safinamide antiparkinson agent CACNA1BSafinamide antiparkinson agent CACNA2D1Safinamide antiparkinson agent CACNA2D2Drug Name Indication(s) GeneSafinamide antiparkinson agent CAC B3Safinamide antiparkinson agent CAC B4Safinamide antiparkinson agent MAOBSafinamide antiparkinson agent SCN11ASafinamide antiparkinson agent SCN11ASafinamide antiparkinson agent SCN1ASafinamide antiparkinson agent SCN2ASafinamide antiparkinson agent SCN3ASafinamide antiparkinson agent SCN4ASafinamide antiparkinson agent SCN5ASafinamide antiparkinson agent SCN7ASafinamide antiparkinson agent SCN8ASafinamide antiparkinson agent SCN9A tetrahydrobiopterin for treatment of phenolketonuria NO S3(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 ICAM1SAR 1118 antiinflammatory agent ITGALSAR 1118 antiinflammatory agent ITGB2 saredutant anti depres sant, anxi olyti c TACR2 nabilone analgesic,neuropathic pain,for CNR2 treatment of restlegs legs syndromeDrug Name Indication(s) Gene nabilone analgesic,neuropathic pain,for C R2 treatment of restlegs legs syndromeSaxagliptin antidiabetic DPP4SB1518 antineoplastic agent JAK2SB-559448 thrombopoietic agent MPLSB-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 HDAC9SCH-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 MAPK14SCY-635 for treatment of hepatitis C PP1ASCY-635 for treatment of hepatitis C PP1D scyllo-inositol for treatment of Alzheimer's disease APPR-etodolac antineoplastic agent RXRADrug Name Indication(s) Gene 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 FOLH1SERTINDOLE antipsychotic agent ADRA1ASERTINDOLE antipsychotic agent ADRA1BSERTINDOLE antipsychotic agent ADRA1DSERTINDOLE antipsychotic agent DRD2SERTINDOLE antipsychotic agent HTR2ASERTINDOLE antipsychotic agent HTR2CSERTINDOLE antipsychotic agent HTR6SERTINDOLE antipsychotic agent KC H2 salmeterol bronchodilator ADRB2Quetiapine antip sy choti c agent, anti depres sant DRD2Quetiapine antip sy choti c agent, anti depres sant HTR2AQuetiapine antip sy choti c agent, anti depres sant HTR2BQuetiapine antip sy choti c agent, anti depres sant HTR2CQuetiapine antip sy choti c agent, anti depres sant HTR2CSF1126 antineoplastic agent MTORSF1126 antineoplastic agent PIK3C3SF1126 antineoplastic agent PIK3CASF1126 antineoplastic agent PIK3CADrug Name Indication(s) GeneSF1126 antineoplastic agent PIK3CBSF1126 antineoplastic agent PIK3CDSF1126 antineoplastic agent PIK3CDSF1126 antineoplastic agent PIK3CGSF1126 antineoplastic agent PIK3CGSF1126 antineoplastic agent PRKDCSGI- 1776 antineoplastic agent PI MlSGI- 1776 antineoplastic agent PIM2SGI- 1776 antineoplastic agent PIM3 beclomethasone antiinflammatory R3C1 agent, glucocorti coi dSGX523 antineoplastic agent MET sibutramine appetite suppressant SLC6A2 sibutramine appetite suppressant SLC6A3 sibutramine appetite suppressant SLC6A4 sildenafil for treatment of erectile PDE5A dy sfucnti on, antihyp erten si ve agentdoxepin 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 SLC6A2Drug Name Indication(s) Gene doxepin hypnotic SLC6A4Silodosin for treatment of BPH-related urinary ADRA1A symptomssirolimus for treatment of wet age-related FKBP1A macular degenerationsirolimus for treatment of wet age-related MTOR macular degenerationsirolimus immunosuppressant FKBP1A sirolimus immunosuppressant MTORSitagliptin antidiabetic DPP4 sivelestat for treatment of acute lung injury ELA2 associated with systemicinflammatory response syndrome(SIRS)zaleplon hypnotic GABRA1 zaleplon hypnotic TSPO fluticasone antiinflammatory R3C1 agent, glucocorti coi dformoterol bronchodilator ADRB2 amphetamine for treatment of cognitive SLC18A2 dysfunction, for treatment of ADHDamphetamine for treatment of cognitive SLC6A3 dysfunction, for treatment of ADHDamphetamine for treatment of cognitive TAARl dysfunction, for treatment of ADHDdextroamphetamine for treatment of ADHD SLC18A2 dextroamphetamine for treatment of ADHD SLC6A2 dextroamphetamine for treatment of ADHD SLC6A3Drug Name Indication(s) GeneSLx-2101 antihypertensive agent,for treatment PDE5A of erectile dysfunctionSLx-4090 antidyslipidaemic agent MTTPSNS-032 antineoplastic agent CDK2SNS-032 antineoplastic agent CDK7SNS-032 antineoplastic agent CDK9SNS-314 antineoplastic agent AURKASNS-314 antineoplastic agent AURKBSNX-5422 antineoplastic agent HSP90AA1SNX-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, antiincontinenceagentSolifenacin for treatment of incontinence CHRM1Solifenacin for treatment of incontinence CHRM2Solifenacin for treatment of incontinence CHRM3Solifenacin for treatment of incontinence CHRM4Solifenacin for treatment of incontinence CHRM5SOU-001 for treatment of incontinence ADRAIASOU-001 for treatment of incontinence ADRAIBDrug Name Indication(s) GeneSOU-001 for treatment of incontinence ADRA 1 DSOU-003 for treatment of incontinence AVPR2 doxorubicin antineoplastic agent TOP2A carbamazepine for treatment of bipolar disorder SCN5A mesal amine for treatment of ulcerative colitis ALOX5 mesal amine for treatment of ulcerative colitis CHUK mesal amine for treatment of ulcerative colitis IKBKB mesal amine for treatment of ulcerative colitis PPARG mesal amine for treatment of ulcerative colitis PTGS1 mesal amine for treatment of ulcerative colitis PTGS2 allopurinol antiuricemic agent XDHSPP676 antihypertensive agent RENResveratrol anti di ab eti c, antineopl asti c agent PDE4BResveratrol anti di ab eti c, antineopl asti c 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 CASRSTX107 for treatment of Fragile X symptoms GRM5 sucralfate antiulcer agent PGA3 sufentanil analgesic OPRD1 sufentanil analgesic OPRK1 sufentanil analgesic OPRM1Drug Name Indication(s) Gene sufentanil analgesic OPRD1 sufentanil analgesic OPRK1 sufentanil analgesic OPRM1 sulfasalazine antiinflammatory agent,DMARD AC ATI 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 SERPIND1Sumatriptan antimigraine agent HTR1ASumatriptan antimigraine agent HTR1BSumatriptan antimigraine agent HTR1DSumatriptan antimigraine agent HTR1FSumatriptan antimigraine agent HTR1ASumatriptan antimigraine agent HTR1BSumatriptan antimigraine agent HTR1DSumatriptan antimigraine agent HTR1FSumatriptan antimigraine agent HTR1ASumatriptan antimigraine agent HTR1BSumatriptan antimigraine agent HTR1DSumatriptan antimigraine agent HTR1F surinabant smoking-cessation agent C R1 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 KITDrug Name Indication(s) Gene sunitinib antineoplastic agent PDGFRA sunitinib antineoplastic agent PDGFRB sunitinib antineoplastic agent RETSUVN-502 for treatment of Alzheimer's disease HTR6SVT-40776 for treatment of incontinence CHRM3 tozadenant antiparkinson agent ADORA2A nitisinone antiparkinson agent HPDT-5224 antiinflammatory agent,DMARD JUNT-62 analgesic AD OR A 1 tacrolimus immunosuppressant FKBP1A tacrolimus immunosuppressant FKBP1ATAFA-93 immunosuppressant FRAPlTAK-242 for treatment of sepsis TLR4 dexlansoprazole Proton pump inhibitor ATP4ATAK-442 antithrombotic F10Talabostat for treatment of neutropenia CSF3 talampanel antiparkinson agent,antineoplastic GRIA1 agenttalampanel antiparkinson agent,antineoplastic GRIA2 agenttalampanel antiparkinson agent,antineoplastic GRIA3 agenttalampanel antiparkinson agent,antineoplastic GRIA4 agenttalarozole antipsoriatic agent,for treatment of CYP26A1 acnetalarozole antipsoriatic agent,for treatment of CYP26B1 acneDrug Name Indication(s) Gene talarozole antipsoriatic agent,for treatment of CYP26C1 acnetalnetant antipsychotic agent TACR3 talotrexin antineoplastic agent DHFRTamibarotene antineoplastic agent RARATamibarotene antineoplastic agent RARB tamsulosin for treatment of urinary symptoms ADRA1A associated with BPHtamsulosin for treatment of urinary symptoms ADRA1B associated with BPHtamsulosin for treatment of urinary symptoms ADRA1D associated with BPHtandutinib antineoplastic agent FLT3Tanespimycin antineoplastic agent HSP90AA1Tanespimycin antineoplastic agent HSP90AB1 tapentadol analgesic OPRM1 tapentadol analgesic SLC6A2 tapentadol analgesic,opioid MORTaranabant anti obesity agent, smoking-cessati on C R1 agenterlotinib antineoplastic agent EGFR tariquidar adjuvant to chemotherapy ABCBlTAS-108 antineoplastic agent ESR1TAS-108 antineoplastic agent ESR2 tasimelteon hypnotic MTNR1A tasimelteon hypnotic MTNR1BTasocitinib antiinflammatory agent,DMARD JAK3Drug Name Indication(s) Gene tazarotene antipsoriatic agent,for treatment of RARA acnetazarotene antipsoriatic agent,for treatment of RARB acnetazarotene antipsoriatic agent,for treatment of RARG acnetazarotene antipsoriatic agent,for treatment of RXRB acneTBR-652 antiviral agent,HIV CCR5 ispronicline nootropic CHRNA4 ispronicline nootropic CHRNB2TC-2403-12 for treatment of ulcerative colitis CHRNA4TC-2403-12 for treatment of ulcerative colitis CHRNB2TC-2696 analgesic CHRNA4TC-2696 analgesic CHRNB2TC-5214 antidepressant CHRNA4TC-5214 antidepressant CHRNB2TC-5619 neuroprotectant CHRNA7TC-6499 analgesic,neuropathic pain CHRNA4TC-6499 analgesic,neuropathic pain CHRNB2TC-6987 antiasthmatic agent, antidiabetic CHRNA7TD-1211 for treatment of opioid-induced OPRM1 gastrointestinal side-effectstecadenoson antiarrhytmic agent AD OR A 1 tecarfarin antithrombotic VKORC1 tegaserod motilitant HTR4 telatinib antineoplastic agent FLT1 telatinib antineoplastic agent FLT4Drug Name Indication(s) Gene telatinib antineoplastic agent KDR telatinib antineoplastic agent PDGFRA telatinib antineoplastic agent PDGFRB telmisartan antihypertensive agent AGTR1 temsirolimus antineoplastic agent FRAP 1 terguride for treatment of pulmonary arterial HTR2A hypertensionterguride for treatment of pulmonary arterial HTR2B hypertensionteriflunomide for treatment of multiple sclerosis DHODH terlipressin for treatment of hepatorenal AVPR1A syndrometerlipressin for treatment of hepatorenal AVPR1B syndrometerlipressin for treatment of hepatorenal AVPR2 syndrometesetaxel antineoplastic agent BCL2 tesetaxel antineoplastic agent TUBB1 tesmilifene adjuvant to chemotherapy ABCBl 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 ARof female sexual dysfunctiontestosterone for treatment of female sexual ARdysfunctionDrug Name Indication(s) Gene testosterone hormone replacement AR testosterone for treatment of female sexual ARdysfunctiontestosterone hormone replacement AR testosterone hormone replacement AR testosterone for treatment of female sexual ARdysfunctiontetrabenazine 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 GRIK5TG-0054 adjuvant to stem cell transplantation CXCR4TG02, SB 1317 antineoplastic agent CDK2Drug Name Indication(s) GeneTG02, SB 1317 antineoplastic agent ERK5TG02, SB 1317 antineoplastic agent FLT3TG02, SB 1317 antineoplastic agent JAK2TG101348 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 hypertensionketoprofen 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 CHRM5Ticagrelor antithrombotic P2RY12 tideglusib for treatment of Alzheimer's disease GSK3A tideglusib for treatment of Alzheimer's disease GSK3B tilarginine for treatment of cardiogenic shock NOS2Drug Name Indication(s) Gene tiotropium for treatment of cystic fibrosis,for CHRM1 treatment of chronic obstructivepulmonary disorder (COPD)tiotropium for treatment of cystic fibrosis,for CHRM2 treatment of chronic obstructivepulmonary disorder (COPD)tiotropium for treatment of cystic fibrosis,for CHRM3 treatment of chronic obstructivepulmonary 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 GSTP1TLN-4601 antineoplastic agent TSPO obinepitide antiobesity agent PY2R obinepitide antiobesity agent PPYR1TM30339 antiobesity agent PPYR1TM38837 antiobesity agent C R1 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 CHRM4Drug Name Indication(s) Gene tolterodine for treatment of incontinence CHRM5 tolvaptan antihypertensive agent AVPR2Tonabersat antimigraine agent HTR1D alprostadil for treatment of erectile PTGER1 dysfunction, for treatment of sexualdysfunction in womenalprostadil for treatment of erectile PTGER2 dysfunction, for treatment of sexualdysfunction in womenmenadione for reducing EGFR-inhibitor- GGCXinduced dermatological side effectsmenadione for reducing EGFR-inhibitor- VKORC1 induced dermatological side effectsmenadione for reducing EGFR-inhibitor- VKORC1L1 induced dermatological side effectstestosterone hormone replacement AR topiramate anticonvulsant CA2 topiramate anticonvulsant CA4 topiramate anticonvulsant GABRA1 topiramate anticonvulsant GRIK1 topiramate anticonvulsant SCN1A topiramate anti convul sant, antimigrai ne agent CA2 topiramate anti convul sant, antimigrai ne agent CA4 topiramate anti convul sant, antimigrai ne agent GABRA1 topiramate anti convul sant, antimigrai ne agent GRIK1 topiramate anti convul sant, antimigrai ne agent SCN1A topotecan antineoplastic agent TOPITorcetrapib antidyslipidaemic agent CETPDrug Name Indication(s) Gene morphine analgesic OPRD1 morphine analgesic OPRK1 morphine analgesic OPRM1 bosentan for treatment of pulmonary arterial EDNRA hypertensionbosentan for treatment of pulmonary arterial EDNRB hypertensiontramadol 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 SLC6A2Drug Name Indication(s) Gene tramadol analgesic SLC6A2 tramadol analgesic SLC6A4 tramadol analgesic SLC6A4 homotaurine 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 CHRM3Drug Name Indication(s) Gene oxycodone analgesic OPRD1 oxycodone analgesic OPRK1 oxycodone analgesic OPRM1 fentanyl analgesic OPRD1 fentanyl analgesic OPRM1 timolol for treatment of glaucoma ADRB 1 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 claudicationtrelanserin for treatment of intermittent HTR2A claudicationtretinoin for treatment of acne RARG tretinoin for treatment of acne RXRB tretinoin for treatment of acne RXRG triamcinolone for treatment of diabetic macular R3C1 edemaTriapine antineoplastic agent RRM2 amlodipine antihypertensive agent CACNA1C amlodipine antihypertensive agent CACNA1D amlodipine antihypertensive agent CACNA1 S amlodipine antihypertensive agent CACNA2D1 amlodipine antihypertensive agent CAC B2 hy drochl orothi azi de antihypertensive agent SLC12A3Drug Name Indication(s) Gene olmesartan antihypertensive agent AGTR1 triciribine antineoplastic agent AKT1 triciribine antineoplastic agent AKT2 triciribine antineoplastic agent AKT3HE3286 antiinflammatory agent,DMARD R3C1 trodusquemine antiobesity agent PTPN1 trospium for treatment of incontinence CHRM1TTP889 anticoagulant F9 lapatinib antineoplastic agent EGFR lapatinib antineoplastic agent ERBB2TZP-101 for treatment of gastroparesis GHSRTZP-102 for treatment of gastroparesis GHSR heparin for treatment of pelvic pain of F10bladder origin and interstitital cystitisheparin for treatment of pelvic pain of SERPINC1 bladder origin and interstitital cystitislidocaine for treatment of pelvic pain of SCN10A bladder origin and interstitital cystitislidocaine for treatment of pelvic pain of SCN5A bladder origin and interstitital cystitislidocaine for treatment of pelvic pain of SCN9A bladder origin and interstitital cystitisudenafil for treatment of erectile dysfunction PDE5A tegafur antineoplastic agent TYMSUlipristal contraceptive PGR heparin antithrombotic F10 heparin antithrombotic SERPINC1Drug Name Indication(s) Gene ursodeoxycholic acid for prevention of recurrence of AKR1C2 colorectal polypstopiramate anticonvulsant CA2 topiramate anticonvulsant CA4 topiramate anticonvulsant GABRA1 topiramate anticonvulsant GRIK1 topiramate anticonvulsant SCN1A buprenorphine antidepressant, analgesic,for OPRD1 treatment of opioid addictionbuprenorphine antidepressant, analgesic,for OPRK1 treatment of opioid addictionbuprenorphine antidepressant, analgesic,for OPRM1 treatment of opioid addictioncarbidopa antiparkinson agent DDC melevodopa antiparkinson agent DRD1 melevodopa antiparkinson agent DRD2 melevodopa antiparkinson agent DRD3 melevodopa antiparkinson agent DRD4 melevodopa antiparkinson agent DRD5V158866 analgesic FAAHV24343 antiobesity agent C R1V3381 analgesic,neuropathic pain GRIN1V3381 analgesic,neuropathic pain GRIN2AV3381 analgesic,neuropathic pain GRIN2BV3381 analgesic,neuropathic pain GRIN2CV3381 analgesic,neuropathic pain GRIN2DV3381 analgesic,neuropathic pain GRIN3AV3381 analgesic,neuropathic pain GRIN3BDrug Name Indication(s) GeneV3381 analgesic,neuropathic pain MAOAV3381 analgesic,neuropathic pain MAOBVA106483 for treatment of BPH-related urinary AVPR2 symptomsVA111913 for treatment of dysmenorrhea AVPR1AVA111913 for treatment of dysmenorrhea AVPR1BVA111913 for treatment of dysmenorrhea AVPR2Vadimezan antineoplastic agent HIPK2Vadimezan antineoplastic agent KDRVadimezan antineoplastic agent PIM3 valproic acid anticonvulsant ABAT valproic acid anticonvulsant ACAD SB valproic acid anticonvulsant HDAC9 valproic acid for treatment of basal cell carcinoma ABAT valproic acid for treatment of basal cell carcinoma ACAD SB 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 bleedingvapreotide for treatment of liver cirrhosis- SSTR5 related variceal bleedingvardenafil 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 CHRNB4Drug Name Indication(s) Gene 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 PGRVatalanib antineoplastic agent FLT1Vatalanib antineoplastic agent FLT4Vatalanib antineoplastic agent KDRVatalanib antineoplastic agent KITVatalanib antineoplastic agent PDGFRAVatalanib antineoplastic agent PDGFRBVatalanib antineoplastic agent FLT1Vatalanib antineoplastic agent FLT4Vatalanib antineoplastic agent KDRVatalanib antineoplastic agent KITVatalanib antineoplastic agent PDGFRAVatalanib antineoplastic agent PDGFRBVEL-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 anti depres sant, app eti te SLC6A2 suppressant, smoking-cessati on agentDrug Name Indication(s) Gene bupropion anti depres sant, app eti te SLC6A3 suppressant, smoking-cessati on agentvelneperit antiobesity agent PY5R velusetrag motilitant HTR4 fluticasone furoate antiinflammatory R3C1 agent, glucocorti coi dverapamil antihypertensive agent CACNA1C verapamil antihypertensive agent CACNA1D verapamil antihypertensive agent CACNA1F verapamil antihypertensive agent CACNA1 S verapamil antihypertensive agent CAC B1 verapamil antihypertensive agent CAC B2 verapamil antihypertensive agent CAC B3 verapamil antihypertensive agent CAC B4 vestipitant for treatment of tinnitus,hypnotic TACR1VGX-1027 antiinflammatory agent,DMARD unknownVIA-2291 antiatherosclerotic agent ALOX5VIA-3196 antidyslipidaemic agent THRBCalcitonin 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 IL17EVigabatrin for treatment of addiction ABATDrug Name Indication(s) GeneVigabatrin for treatment of addiction GABBR1 vilazodone antidepressant HTR1A vildagliptin antidiabetic DPP4 vincristine antineoplastic agent TUBA4A vincristine antineoplastic agent TUBB vinorelbine antineoplastic agent TUBBΒΠΒ014 antiparkinson agent ADORA2AVirulizin antineoplastic agent IL12AVirulizin antineoplastic agent IL12B naltrexone for treatment of substance abuse OPRD1 naltrexone for treatment of substance abuse OPRK1 naltrexone for treatment of substance abuse OPRM1Voclosporin antiinflammatory PPIAagent,DMARD,immunosuppressantVoclosporin antiinflammatory PPP3CA agent,DMARD,immunosuppressantVoclosporin antiinflammatory PPP3CB agent,DMARD,immunosuppressantVoclosporin antiinflammatory PPP3CC agent,DMARD,immunosuppressantvofopitant for treatment of post-traumatic stress TACR1 disorder,hypnoticvoglibose antidiabetic MGAM volinanserin hypnotic HTR2A vorapaxar cardiovascular agent F2R vorapaxar cardiovascular agent F2RL2 vorapaxar cardiovascular agent F2RL3Voreloxin antineoplastic agent TOP2ADrug Name Indication(s) GeneVoreloxin antineoplastic agent TOP2BHistrelin antineoplastic agent GNRHRHistrelin antineoplastic agent GNRHR2TRPV1 antagonist analgesic TRPV1VR-147 antimigraine agent HTR1BVR-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 ADRB 1VTP-27999 antihypertensive agent RENVTX-1463 antiallergy agent TLR8VTX-2337 antineoplastic agent TLR8VX-509 antiinflammatory agent,DMARD JAK3WX-554 antineoplastic agent MAP2K1WX-554 antineoplastic agent MAP2K2WX-554 antineoplastic agent MAP2K3WX-554 antineoplastic agent MAP2K4WX-554 antineoplastic agent MAP2K5WX-554 antineoplastic agent MAP2K6WX-554 antineoplastic agent MAP2K7 tozasertib antineoplastic agent AURKA tozasertib antineoplastic agent AURKB tozasertib antineoplastic agent AURKCVX-702 antiinflammatory MAPKl l agent,cardiovascular agentDrug Name Indication(s) GeneVX-702 antiinflammatory MAPK12 agent,cardiovascular agentVX-702 antiinflammatory MAPK13 agent,cardiovascular agentVX-702 antiinflammatory MAPK14 agent,cardiovascular agentVX-765 antip sori ati c agent, anti convul sant CASP1 ivacaftor for treatment of cystic fibrosis CFTRVX-809 for treatment of cystic fibrosis CFTR ivacaftor for treatment of cystic fibrosis CFTRVX-809 for treatment of cystic fibrosis CFTRWX-UK1 antineoplastic agent PLAU emzetibe antidyslipidaemic agent PC1L1 emzetibe antidyslipidaemic agent SO ATI simvastatin antidyslipidaemic agent HMGCR RP104 for treatment of ADHD ADRA1B RP104 for treatment of ADHD SLC18A2 RP104 for treatment of ADHD SLC6A3 xaliproden neuroprotectant HTR1AXL019 antineoplastic agent JAK2 cabozantinib antineoplastic agent KDR cabozantinib antineoplastic agent METXL228 antineoplastic agent ABL1XL228 antineoplastic agent AURKAXL228 antineoplastic agent IGF1RXL228 antineoplastic agent SRCXL281 antineoplastic agent ARAFXL281 antineoplastic agent BRAFDrug Name Indication(s) GeneXL281 antineoplastic agent RAF 1XL418 antineoplastic agent AKT1XL418 antineoplastic agent AKT2XL418 antineoplastic agent AKT3XL418 antineoplastic agent RPS6KB1XL647 antineoplastic agent EGFRXL647 antineoplastic agent EPHB4XL647 antineoplastic agent ERBB2XL647 antineoplastic agent FLT1XL647 antineoplastic agent FLT4XL647 antineoplastic agent KDRXL765 antineoplastic agent MTORXL765 antineoplastic agent PIK3CAXL765 antineoplastic agent PIK3CDXL765 antineoplastic agent PIK3CGXL820 antineoplastic agent FLT1XL820 antineoplastic agent FLT4XL820 antineoplastic agent KDRXL820 antineoplastic agent KITXL820 antineoplastic agent PDGFRAXL820 antineoplastic agent PDGFRBXL844 antineoplastic agent CFIEK1XL844 antineoplastic agent CFTEK2XL880 antineoplastic agent KDRXL880 antineoplastic agent METXL888 antineoplastic agent HSP90AA1XL888 antineoplastic agent HSP90AB1XL999 antineoplastic agent AXLDrug Name Indication(s) GeneXL999 antineoplastic agent FGFR1XL999 antineoplastic agent FLT1XL999 antineoplastic agent FLT3XL999 antineoplastic agent FLT4XL999 antineoplastic agent KDRXL999 antineoplastic agent KITXL999 antineoplastic agent PDGFRB camptothecin antineoplastic agent TOPIXMT-1107 antineoplastic agent METAP2 tranexamic acid for treatment of menorrhagia PLGXP13512 for treatment of restless legs CACNA1B syndromeXP13512 for treatment of restless legs CACNA2D1 syndromeXP13512 for treatment of restless legs CACNA2D2 syndromeR-baclofen for treatment of gastrointestinal GABBR1 reflux diseaseR-baclofen for treatment of gastrointestinal GABBR2 reflux diseaseXP21279 antiparkinson agent DRD1XP21279 antiparkinson agent DRD2XP21279 antiparkinson agent DRD3XP21279 antiparkinson agent DRD4XP21279 antiparkinson agent DRD5 gantofiban antithromb oti c, anti athero scleroti c ITGA2B agentDrug Name Indication(s) Gene gantofiban antithromb oti c, anti athero scleroti c ITGB3 agentfinasteride antineoplastic agent AKR1D1 finasteride antineoplastic agent SRD5A1 finasteride antineoplastic agent SRD5A2YM-178 for treatment of overactive bladder ADRB3YM-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 HTR1FDrug Name Indication(s) Gene 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 ABCBl zucapsaicin analgesic TRPV1 hydrocodone analgesic OPRD1 hydrocodone analgesic OPRM1...

Claims

CLAIMSWe claim:

1. A compound of formula I:or a pharmaceutically acceptable salt thereof, wherein:X1is a bivalent moiety selected from a covalent bond, -CH2- -C(O)-, -C(S)-, orR1is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(0)R, -S(0)2R, -NR2, or an optionally substituted C1-4 aliphatic;each R2is independently hydrogen, -R6, halogen, -CN, -N02, -OR, -SR, -NR2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0)NR2, -C(0)N(R)OR, -OC(0)R, -OC(0)NR2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0)NR2, or -N(R)S(0)2R;Ring B is a fused ring selected from 6-membered aryl containing 0-2 nitrogen atoms, 5 to 7- membered partially saturated carbocyclyl, 5 to 7-membered partially saturated heterocyclyl with 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur, or 5- membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur;R3is selected from hydrogen, halogen, -OR, -N(R)2, or -SR;each R4is independently hydrogen, -R6, halogen, -CN, -N02, -OR, -SR, - R2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;R5is hydrogen, Ci-4 aliphatic, or -CN;each R6is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -NR-, - S-, -OC(O)-, -C(0)0-, -C(O)-, -S(O)-, -S(0)2-, -NRS(0)2-, -S(0)2NR-, -NRC(O)-, --, -OC(0)NR-, -NRC(0)0-,, 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, and sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and 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 nitrogen, oxygen, or sulfur;TBM is a target binding moiety;m is 0, 1, 2, 3 or 4;each of n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, or an optionally substituted group selected from Ci-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are 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, and sulfur; wherein said compound of formula I is other than those depicted in Table A-l.

2. A compound of formula II-A:II-Aor a pharmaceutically acceptable salt thereof, wherein:X1is a bivalent moiety selected from a covalent bond, -CH2- -C(O)-, -C(S)-R1is hydrogen, deuterium, halogen, -CN,-S(0)R, -S(0)2R, -NR2, or an optionally substituted C1-4aliphatic;Ringeach R2is independently hydrogen, -R4, halogen, -CN, -NO2, -OR, -SR, - R2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;Ring B is selected from a 6-membered aryl containing 0-2 nitrogen atoms or a 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R3is independently hydrogen, -R4, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0)NR2, -C(0)N(R)OR, -OC(0)R, -OC(0)NR2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0)NR2, or -N(R)S(0)2R;each R4is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;R5is hydrogen, C1-4 aliphatic, or -CN;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -NR-, - S-, -OC(O)-, -C(0)0-, -C(O)-, -S(O)-, -S(0)2-, -NRS(0)2-, -S(0)2NR-, -NRC(O)-, --, -OC(0) R-, - RC(0)0-,, 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, and sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1 -2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and 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 nitrogen, oxygen, or sulfur;TBM is a target binding moiety;m is 0, 1, or 2;n is 0, 1, 2, 3, or 4;p is 0 or 1, wherein when p is 0, the bond connecting Ring A and Ring B is connected toeach of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, or an optionally substituted group selected from Ci-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatomsindependently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are 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, and sulfur;wherein said compound of formula II-A is other than those depicted in Table A-2.

3. A compound of formula II-B:II-Bor a pharmaceutically acceptable salt thereof, wherein:a bivalent moiety selected from a covalent bond, -CH2- -C(O)-, -C(S)-,is hydrogen, deuterium, halogen, -CN, OR, SR, -S(0)R, -S(0)2R, -NR2, or an optionally substituted C1-4aliphatic;Ring - or bicyclic ring selected fromeach R2is independently hydrogen, -R4, halogen, -CN, -NO2, -OR, -SR, - R2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R;Ring B is selected from a 6-membered aryl containing 0-2 nitrogen atoms or a 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; each R3is independently hydrogen, -R4, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(0)2R, -S(0)2NR2, -S(0)R, -C(0)R, -C(0)OR, -C(0)NR2, -C(0)N(R)OR, -OC(0)R, -OC(0)NR2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0)NR2, or -N(R)S(0)2R;each R4is independently an optionally substituted group selected from Ci-6aliphatic, phenyl, a 4- 7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;R5is hydrogen, C1-4 aliphatic, or -CN;L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, -NR-, - S-, -OC(O)-, -C(0)0-, -C(O)-, -S(O)-, -S(0)2-, -NRS(0)2-, -S(0)2NR-, -NRC(O)-, --, -OC(0) R-, - RC(0)0-,, 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, and sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1 -2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and 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 nitrogen, oxygen, or sulfur;TBM is a target binding moiety;m is 0, 1, or 2;n is 0, 1, 2, 3, or 4;p is 0 or 1 ;each of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; andeach R is independently hydrogen, or an optionally substituted group selected from Ci-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur.The compound of claim 1, wherein X1is selected from a covalent bond, -CH2- -C(O)5. The compound of claim 1, wherein R1is hydrogen, deuterium, halogen, -OR, -SR, -S(0)R, -S(0)2R, - R2, or an optionally substituted C1-4aliphatic.The compound of claim 1, wherein Ring A is a bi- or tric d fromwherein Ring B is other than imidazo or benzo,other7. The compound of claim 1, wherein Ring B is selected from 6-membered aryl containing 0-2 nitrogen atoms, 6-membered partially saturated carbocyclyl, or 6-membered partially saturated heterocyclyl with 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur.

8. The compound of claim 1, wherein R3is selected from hydrogen, halogen, -OR, or - N(R)2.

9. The compound of claim 1, wherein R4is hydrogen, -R6, halogen, -CN, -N02, -OR, - SR, - R2, -S(0)2R, -S(0)2R2, -S(0)R, -C(0)R, -C(0)OR, C(0) R2, -C(0)N(R)OR, -OC(0)R, -OC(0) R2, -N(R)C(0)OR, -N(R)C(0)R, -N(R)C(0) R2, or -N(R)S(0)2R.

10. The compound of claim 1, wherein L is a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, - R-, -S-, -OC(O)-, -C(0)0-, -C(O -, -S(O)-, -S(0)2- - RS(0)2-, -S(0)2R-, --, -C(0) -, -OC(0) R-, - RC(0)0-11. The compound of claim 1, wherein TBM is a target binding moiety that binds to a target protein selected from the group listed in paragraph [00209].12 Th compound of claim 2 or 3, wherein X1is selected from a covalent bond, -CH2- -13. The compound of claim 2 or 3, wherein wherein R1is hydrogen, deuterium, halogen, - OR, -SR, -S(0)R, -S(0)2R, - R2, or an optionally substituted Ci-4aliphatic.

15. The compound of claim 2 or 3, wherein Ring B is a 6-membered aryl containing 0-2 nitrogen atoms.

16. The compound of claim 2 or 3, wherein p is 0.

17. The compound of claim 2 or 3, wherein L is a bivalent, saturated or unsaturated, straight or branched Ci-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by -Cy-, -0-, - R-, -S-, -OC(O)-, -C(0)0-, -C(O)-, -S(O)-, -S(0)2-, - RS(0)2-, --, -NRC(0 , -C(0)NR-, -OC(0)NR-, -NRC(0)0-18. The compound of claim 2 or 3, wherein TBM is a target binding moiety that binds to a target protein selected from the group listed in paragraph [00256].

19. The compound of claim 1, 2 or 3, wherein said compound is selected from those depicted in Table 1 of the specification, or a pharmaceutically acceptable salt thereof.

20. A pharmaceutical composition comprising a compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

21. A method of degrading a target protein in a biological sample comprising contacting the sample with the compound of any one of claims 1-19, or a pharmaceutically acceptable salt thereof, wherein the target protein is selected from the group listed in paragraph [00256].

22. A method of treating a target protein-mediated disorder, disease, or condition in a patient comprising administering to said patient the pharmaceutical composition of claim 13.

23. The method of claim 22, wherein the disorder is selected from an autoimmune disorder, an inflammatory disorder, a proliferative disorder, an endocrine disorder, a neurological disorder, or a disorder associated with transplantation.

24. The method of claim 23, wherein the disorder is a proliferative disorder.

25. The method of claim 24, wherein the proliferative disorder is a cancer.

26. The method of claim 25, wherein the cancer is 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; multiple myeloma, 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 or teratocarcinomas, 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.