Protein-degrading agents and their use

Abstract

To provide a method for treating a disease. [Solution] The present invention provides compounds, compositions thereof, and methods for using them for targeted degradation of proteins and for treating protein-mediated disorders. The present invention relates particularly to compounds and methods useful for regulating targeted ubiquitination of various polypeptides and other proteins that are degraded and / or otherwise inhibited by the compounds according to the present invention. The present invention also provides pharmaceutically acceptable compositions comprising the compounds of the present invention, and methods for using said compositions in the treatment of various disorders.

Description

[Technical Field]

[0001] Field of Invention The present invention relates to compounds and methods useful for regulating targeted ubiquitination, particularly with respect to various polypeptides and other proteins that are degraded and / or otherwise inhibited by the compounds of the present invention. The present invention also provides pharmaceutically acceptable compositions comprising the compounds of the present invention, and methods for using said compositions in the treatment of various disorders. [Background technology]

[0002] Background of the Invention The ubiquitin-proteasome pathway (UPP) is a critical pathway that regulates major regulator proteins and degrades misfolded or abnormal proteins. The UPP is central to numerous cellular processes, and its deficiency or imbalance can lead to the development of various diseases. The covalent binding of ubiquitin to specific protein substrates is achieved through the action of E3 ubiquitin ligases. These ligases comprise over 500 different proteins and are classified into several classes, defined by the structural elements of their E3 functional activity.

[0003] Cereblon (CRBN) interacts with damaged DNA-binding protein 1 and forms an E3 ubiquitin ligase complex with culin 4, which functions as a substrate receptor, allowing proteins recognized by CRBN to be ubiquitinated and degraded by the proteasome.

[0004] Proteasome-mediated degradation of unnecessary or damaged proteins plays a crucial role in maintaining normal cellular function (e.g., cell survival, proliferation, and growth). A new role for CRBNs has been identified: the binding of immunomodulatory drugs (IMiDs) (e.g., thalidomide) to CRBNs is linked to the teratogenic and cytotoxic effects of IMiDs (including lenalidomide, widely used to treat patients with multiple myeloma). CRBNs likely play a major role in the binding, ubiquitination, and degradation of factors involved in maintaining the function of myeloma cells. These new findings regarding the role of CRBNs in IMiD activity have stimulated keen research into downstream factors of CRBNs involved in maintaining normal cellular function (Chang and Stewart Int J Biochem Mol Biol. 2011;2(3):287-294).

[0005] UPPs play a major role in the degradation of short-lived regulatory proteins crucial for various fundamental cellular processes, including cell cycle regulation, regulation of cell surface receptors and ion channels, and antigen presentation. Their pathways are involved in the pathogenesis of several forms of malignancy, several genetic disorders (including cystic fibrosis, Angelman syndrome, and Liddle syndrome), immune surveillance / viral disease, and muscle wasting pathologies. Many diseases are associated with abnormal UPPs, which negatively impact the regulation of the cell cycle and division, cellular responses to stress and extracellular modulators, neural network morphogenesis, cell surface receptors, ion channels, secondary pathways, DNA repair, and organelle biodevelopment.

[0006] Abnormalities in this process have recently been associated with the development of several diseases, both congenital and acquired. These diseases fall into two main groups: (a) specific protein (b) Diseases resulting from the loss of function that leads to quality stabilization, and (b) diseases resulting from the acquisition of function (i.e., abnormal or accelerated degradation of protein targets).

[0007] UPP is used to induce selective proteolysis and involves the use of fusion proteins to artificially ubiquitinate target proteins and synthetic small molecule probes to induce proteasome-dependent degradation. Bifunctional compounds consisting of a target protein-binding ligand and an E3 ubiquitin ligase ligand induced proteasome-mediated degradation of selected proteins via recruitment to these E3 ubiquitin ligases and subsequent ubiquitination. These drug-like molecules offer the possibility of transient control of protein expression. Such compounds can induce inactivation of the protein of interest upon addition to cells or administration to animals or humans, can be useful as biochemical reagents, and can provide 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). In the art, there remains a continuing need for effective treatment of diseases, particularly hyperplasia and cancer, such as multiple myeloma. However, non-specific effects and the inability to target and regulate certain classes of proteins (e.g., transcription factors) together remain obstacles to the development of effective anti-cancer agents. Therefore, small molecule therapeutic agents that specifically affect or enhance the substrate of cereblon and are "tunable" such that a broad class of proteins can be specifically targeted and regulated are highly useful as therapeutic agents. Accordingly, there remains a need to find bifunctional compounds that are proteolytic agents useful as therapeutic agents.

Prior Art Documents

Non-Patent Documents

[0008]

Non-Patent Document 1

[0009] Summary of the Invention This application relates to novel bifunctional compounds that function to recruit targeted proteins to E3 ubiquitin ligases for degradation, as well as methods for preparing and using these compounds. In particular, this disclosure provides bifunctional compounds that find utility as modulators of targeted ubiquitination of various polypeptides and other proteins (which are then degraded and / or otherwise inhibited by the bifunctional compounds described herein). The advantage of the compounds provided herein is that they enable a wide range of pharmacological activities and are compatible with the degradation / inhibition of targeted polypeptides derived from virtually any class or family of proteins. Furthermore, this specification provides methods for using effective amounts of the compounds described herein for the treatment or mitigation of disease conditions such as cancer, e.g., multiple myeloma.

[0010] This application further relates to the targeted degradation of proteins by the use of a bifunctional molecule (a bifunctional molecule in which the cerebron-binding portion is linked to a ligand that binds to the targeted protein).

[0011] This application also has the following structure: [ka] With regard to a bifunctional compound having, here TBMs are target-binding sites that can bind to one or more targeted proteins; L is the divalent part that connects TBM to UBM; and UBM is a ubiquitin binding site (e.g., cereblon) that can bind to ubiquitin ligases such as E3 ubiquitin ligase.

[0012] The compounds of the present invention, and their pharmaceutically acceptable compositions, are found to be effective for the modulation of targeted ubiquitination. Such compounds are of general formula I: [ka] or a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described herein.

[0013] It has also been found that other compounds of the present invention, and their pharmaceutically acceptable compositions, are effective for the modulation of targeted ubiquitination. Such compounds have the general formula I'': [ka] 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 the present invention, and their pharmaceutically acceptable compositions, are effective for the modulation of targeted ubiquitination. Such compounds have general formula II-A: [ka] or a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described herein.

[0015] It has also been found that other compounds of the present invention, and their pharmaceutically acceptable compositions, are effective for the modulation of targeted ubiquitination. Such compounds have the general formula II''-A: [ka] or a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described herein.

[0016] It has also been found that other compounds of the present invention, and their pharmaceutically acceptable compositions, are effective for the modulation of targeted ubiquitination. Such compounds have general formula II-B: [ka] or a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described herein.

[0017] It has also been found that other compounds of the present invention, and their pharmaceutically acceptable compositions, are effective for the modulation of targeted ubiquitination. Such compounds have the general formula II''-B: [ka] or a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described herein.

[0018] The compounds of the present invention and their pharmaceutically acceptable compositions are useful for treating various diseases, disorders, or conditions. Such diseases, disorders, or conditions are listed herein.

[0019] The compounds provided by the present invention are also useful for the study of CRBN and targeted proteins in biological and pathological phenomena; for the study of CRBN and targeted proteins occurring in body tissues; and for the comparative evaluation of novel CRBN or targeted proteins, or other regulators of CRBN or targeted proteins, in vitro or in vivo. [Modes for carrying out the invention]

[0020] Detailed description of a specific embodiment 1. General description of specific embodiments of the present invention: The compounds and compositions of the present invention are useful for regulating targeted ubiquitination.

[0021] Where defined herein, the terms “binding agent,” “modulator,” and “ligand” describe compounds that are interchangeable and that bind to, modulate, or are ligands for CRBN or the targeted protein.

[0022] In a particular embodiment, the present invention relates to formula I: [ka] Provides a compound or a pharmaceutically acceptable salt thereof, in formula I: X 1 These are covalent bonds, -CH2-, -C(O)-, -C(S)-, or [ka] It is the bivalent part selected from; R 1 C is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, or substituted as needed. 1~4 It is aliphatic; Each R 2 These are independently hydrogen, -R 6 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Ring A is, [ka] A biring or triring ring selected from, where Ring B is a fused ring selected from a 6-membered aryl containing 0 to 2 nitrogen atoms, a 5- to 7-membered partially saturated carbocyclic ring, a 5- to 7-membered partially saturated heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen or sulfur, or a 5-membered heteroaryl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen or sulfur; R 3 is selected from hydrogen, halogen, -OR, -N(R)2, or -SR; Each R 4 is independently hydrogen, -R 6 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; R 5 is hydrogen, C 1~4 aliphatic, or -CN; Each R 6 is independently C 1~6 aliphatic, phenyl, a 4- to 7-membered saturated or partially unsaturated heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a group optionally substituted; selected from; L is a covalent bond, or a divalent, saturated or unsaturated, straight-chain or branched-chain C 1~50 hydrocarbon chain, where 0 to 6 methylene units of L are independently -Cy-, -O-, -N(R)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-

Chemical formula

[0023] In a particular embodiment, the present invention relates to formula I': [ka] Provides a compound or a pharmaceutically acceptable salt thereof, in formula I': X 1 These are covalent bonds, -CH2-, -C(O)-, -C(S)-, or [ka] It is the bivalent part selected from; R 1 C is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, or substituted as needed. 1~4 It is aliphatic; Each R 2 These are independently hydrogen, -R 6 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Ring A is such that Ring B is not imidazo or benzo. [ka] , [ka] Ring B is not benzo. [ka] Ring B is not benzo. [ka] , [ka] Ring B is not benzo. [ka] [ka] A biring or triring ring selected from, where Ring B is a fused ring selected from a 6-membered aryl containing 0 to 2 nitrogen atoms, a 5- to 7-membered partially saturated carbocyclyl, a 5- to 7-membered partially saturated heterocyclyl having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5-membered heteroaryl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 3 This is selected from hydrogen, halogen, -OR, -N(R)2, or -SR; Each R 4 These are independently hydrogen, -R 6 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)N R2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; R 5 is hydrogen, C 1~4 It is aliphatic or -CN; Each R 6 C 1~6 A optionally substituted group selected from a 4- to 7-membered saturated or partially unsaturated heterocyclic ring having one or two heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered heteroaryl ring having one or four heteroatoms independently selected from nitrogen, oxygen, and sulfur; L is a covalent or divalent, saturated or unsaturated, linear or branched C 1~50It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of each other: -Cy-, -O-, -N(R)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by, here: Each -Cy- is independently a phenylenyl, an 8- to 10-membered bicyclic aryrenyl, a 4- to 7-membered saturated or partially unsaturated carbocyclilenyl, a 4- to 7-membered saturated or partially unsaturated spirocarbocyclilenyl, an 8- to 10-membered bicyclic saturated or partially unsaturated carbocyclilenyl, a 4- to 7-membered saturated or partially unsaturated heterocyclilenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 4- to 7-membered saturated cyclilenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur. A optionally substituted divalent ring selected from a summed or partially unsaturated spiroheterolenyl, an 8- to 10-membered bicyclic saturated or partially unsaturated heterocyclenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered heteroaryrenyl having one or four heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryrenyl having one or five heteroatoms independently selected from nitrogen, oxygen, or sulfur; TBM is the target binding site; m is 0, 1, 2, 3, or 4; Each of n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and Each R is independently a hydrogen atom or a optionally substituted group, and this optionally substituted group is C 1~6Selected from 4- to 7-membered saturated or partially unsaturated heterocyclic rings having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and 5- to 6-membered heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same nitrogen atom, together with the atom between them, form a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to this nitrogen atom.

[0024] In a particular embodiment, the present invention relates to formula I'': [ka] Provides a compound or a pharmaceutically acceptable salt thereof, in formula I'': X 1 These are covalent bonds, -C(R)2-, -C(O)-, -C(S)-, -P(O)(OR)-, -P(O)(R)-, -P(O)(NR2)-, -S(O)-, -S(O)2-, or [ka] It is the bivalent part selected from; X 2 is a carbon or silicon atom; X 3 is a divalent part selected from -C(R)2-, -N(R)-, -CF2-, -CHF-, -S-, or -O-; X 4 is a divalent part selected from a covalent bond or -C(R)2-; [ka] It is either a single bond or a double bond; R 1This includes hydrogen, deuterium, halogens, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, -P(O)(OR)2, -P(O)(NR2)OR, -P(O)(NR2)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, and substituted C as needed. 1~4 It is aliphatic, or: R 1 and X 1 or X 4 These atoms, together with the atoms in between, form a 5- to 7-membered saturated, partially unsaturated carbocyclic ring, or a heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Each R 2 These are independently hydrogen, deutherium, and -R 6 , halogen, -CN, -NO2, -OR, -SR, -NR2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, - OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)S(O)2NR2, -P(O)(OR)2, -P(O)(NR2)OR, or -P(O)(NR2)2; Ring A is, [ka] A biring or triring ring selected from, where Ring B is a condensed ring selected from a 6-membered aryl containing 0 to 3 nitrogen atoms, a 5- to 7-membered partially saturated carbocyclyl, a 5- to 7-membered partially saturated heterocyclyl having 1 to 3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 5-membered heteroaryl having 1 to 3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur; R 3These are hydrogen, deuterium, halogen, -CN, -NO2, -OR, -NR2, -SR, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NR(OR), -OC(O)R, -OC(O)NR2, -OP(O)(OR)2, -OP(O)(NR2)2, -OP(O)(OR)NR2, -N(R) Selected from C(O)R, -N(R)C(O)OR, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)S(O)2NR2, -N(R)P(O)(OR)2, -N(R)P(O)(OR)NR2, -P(O)(OR)2, -P(O)(NR2)OR, -P(O)(NR2)2, -Si(OH)2R, -Si(OH)(R)2, or -Si(R)3; Each R 4 These are independently hydrogen, deutherium, and -R 6 , halogen, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -P(O)(OR)2, -P(O)(NR2)OR, or -P(O)(NR2)2; R 5 This consists of hydrogen, deutherium, and optionally substituted C. 1~4 Aliphatic, or -C N is; Each R 6 C 1~6 A optionally substituted group selected from aliphatic, phenyl, boron, nitrogen, oxygen, silicon, or sulfur-independently saturated or partially unsaturated heterocyclic rings of 4 to 7 members having 1 to 3 heteroatoms, and 5 to 6 membered heteroaryl rings having 1 to 4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur; L is a covalent or divalent, saturated or unsaturated, linear or branched C 1~50It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of -Cy-, -O-, -N(R)-, -Si(R)2-, -Si(OH)(R)-, -Si(OH)2-, -P(O)(OR)-, -P(O)(R)-, -P(O)(NR2)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by, here: Each -Cy- independently comprises phenylenyl, 8- to 10-membered bicyclic aryrenyl, 3- to 8-membered saturated or partially unsaturated carbocyclilenyl, 6- to 11-membered saturated or partially unsaturated spirocarbocyclilenyl, 5- to 12-membered, bridged or unbridged, bicyclic saturated or partially unsaturated carbocyclilenyl, 4- to 10-membered saturated or partially unsaturated heterocyclilenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, and 6- to 11-membered saturated cyclilenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur. Alternatively, a substituted divalent ring, optionally selected from a partially unsaturated spiroheterocrylenyl, a 5- to 12-membered bridged or unbridged bicyclic saturated or partially unsaturated heterocyclenyl, a 5- to 6-membered heteroarylenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, or an 8- to 10-membered bicyclic heteroarylenyl having 1 to 5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur; TBM is the target binding site; m is 0, 1, 2, 3, or 4; Each of n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and Each R is independently a hydrogen, deuterium, or optionally substituted group, and this optionally substituted group is C 1~6 Selected from 4- to 7-membered saturated or partially unsaturated heterocyclic rings having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and 5- to 6-membered heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same nitrogen atom, together with the atom between them, form a 4-membered system with 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to this nitrogen atom. They form saturated, partially unsaturated, or heteroaryl rings with approximately 7 members.

[0025] [ka] If the connection point is shown on ring B, [ka] The bonding site can be on ring A, and it is assumed that it can be on any available carbon or nitrogen atom on ring A, including the ring to which ring B is fused, and this will be understood by those skilled in the art. [ka] However, R 4 or R 5 When bonded to a nitrogen atom, R 4 or R 5 It does not exist, and [ka] However, R 4 Base or R 5 To replace the basis. [ka] However, R 3 When bonded to a carbon atom, R 3It does not exist, and [ka] However, R 3 To replace the basis. For example, for the purpose of clarification, [ka] If it is bonded to ring B, then ring A is [ka] and; [ka] If it is bonded to ring A, then ring A is [ka] and; [ka] However, R 4 If it is bonded to the nitrogen atom that is bonded to it, then ring A is [ka] and; [ka] However, R 5 If it is bonded to the nitrogen atom that is bonded to it, then ring A is [ka] and [ka] However, R 3 If it is bonded to a carbon atom that is bonded to it, then ring A is [ka] That is the case.

[0026] -(R 2 ) n If the bonding point is shown on ring B, then -(R 2 ) n The bonding point can be on ring A, and also on any available boron, carbon, nitrogen, or silicon atom on ring A, including the ring to which ring B is fused, and this will be understood by those skilled in the art. -R 2 However, R 4 or R 5 When bonded to a nitrogen atom, R 4 or R 5 It does not exist, and -R 2 However, R 4 Base or R 5 To replace the basis. -R 2 However, R 3 When bonded to a carbon atom, R 3 It does not exist, and -R 2 However, R 3 To replace the basis.

[0027] In a particular embodiment, the present invention relates to formula II-A: [ka] The compound or a pharmaceutically acceptable salt thereof is provided, in formula II-A: X 1 These are covalent bonds, -CH2-, -C(O)-, -C(S)-, or [ka] It is the bivalent part selected from; R 1 C is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, or substituted as needed. 1~4 It is aliphatic; Ring A is, [ka] A monoring or biring ring selected from; Each R 2 These are independently hydrogen, -R 4 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Ring B is selected from a 6-membered aryl group containing 0 to 2 nitrogen atoms, or a 5-membered heteroaryl group containing 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Each R 3 These are independently hydrogen, -R 4 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Each R 4 C 1~6 A optionally substituted group selected from a 4- to 7-membered saturated or partially unsaturated heterocyclic ring having one or two heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered heteroaryl ring having one or four heteroatoms independently selected from nitrogen, oxygen, and sulfur; R 5 is hydrogen, C 1~4 It is aliphatic or -CN; L is a covalent or divalent, saturated or unsaturated, linear or branched C 1~50 It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of each other: -Cy-, -O-, -N(R)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O -, [Chem.] is replaced by, where: Each -Cy- is independently a divalent ring selected from phenylenyl, 8- to 10-membered bicyclic arylenyl, 4- to 7-membered saturated or partially unsaturated carbocyclirenyl, 4- to 7-membered saturated or partially unsaturated spirocarbocyclirenyl, 8- to 10-membered bicyclic saturated or partially unsaturated carbocyclirenyl, 4- to 7-membered saturated or partially unsaturated heterocyclirenyl having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 4- to 7-membered saturated or partially unsaturated spiroheterocyclirenyl having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 8- to 10-membered bicyclic saturated or partially unsaturated heterocyclirenyl having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 5- to 6-membered heteroarylenyl having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 8- to 10-membered bicyclic heteroarylenyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which is optionally substituted; 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, where when p is 0, the bond connecting ring A and ring B is [Chem.] is bonded to; Each q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and Each R is independently hydrogen or an optionally substituted group, and this optionally substituted group is C 1~6Selected from 4- to 7-membered saturated or partially unsaturated heterocyclic rings having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and 5- to 6-membered heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same nitrogen atom, together with the atom between them, form a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to this nitrogen atom.

[0028] In a particular embodiment, the present invention relates to formula II'-A: [ka] The compound or a pharmaceutically acceptable salt thereof is provided, in formula II'-A: X 1 These are covalent bonds, -CH2-, -C(O)-, -C(S)-, or [ka] It is the bivalent part selected from; R 1 C is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, or substituted as needed. 1~4 It is aliphatic; Ring A is, [ka] A monoring or biring ring selected from; Each R 2 These are independently hydrogen, -R 4 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Ring B is selected from 6-membered aryl containing 0 to 2 nitrogen atoms, or 5-membered heteroaryl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen or sulfur ; Each R 3 is independently hydrogen, -R 4 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Each R 4 is independently a group selected from C 1~6 aliphatic, phenyl, a 4- to 7-membered saturated or partially unsaturated heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, which is optionally substituted; R 5 is hydrogen, C 1~4 aliphatic, or -CN; L is a covalent bond or a divalent, saturated or unsaturated, straight-chain or branched-chain C 1~50 hydrocarbon chain, where 0 to 6 methylene units of L are independently -Cy-, -O-, -N(R)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-,

Chemical formula

[0029] In a particular embodiment, the present invention relates to formula II''-A: [ka] Provides a compound or a pharmaceutically acceptable salt thereof, in II''-A: X 1 These are covalent bonds, -C(R)2-, -C(O)-, -C(S)-, -P(O)(OR)-, -P(O)(R)-, -P(O)(NR2)-, -S(O)-, -S(O)2-, or [ka] It is the bivalent part selected from; X 2 is a carbon or silicon atom; X 3 is a divalent part selected from -C(R)2-, -N(R)-, -CF2-, -CHF-, -S-, or -O-; X 4 is a divalent part selected from a covalent bond or -C(R)2-; [ka] It is either a single bond or a double bond; R 1 This includes hydrogen, deuterium, halogens, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, -P(O)(OR)2, -P(O)(NR2)OR, -P(O)(NR2)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, and substituted C as needed. 1~4 It is aliphatic, or: R 1 and X 1 or X 4These atoms, together with the atoms in between, form a 5- to 7-membered saturated, partially unsaturated carbocyclic ring, or a heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Ring A is, [ka] A monoring or biring ring selected from; Each R 2 These are independently hydrogen, deutherium, and -R 6 , halogen, -CN, -NO2, -OR, -SR, -NR2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, - OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)S(O)2NR2, -P(O)(OR)2, -P(O)(NR2)OR, or -P(O)(NR2)2; Ring B is selected from a 6-membered aryl containing 0 to 3 nitrogen atoms, or a 5-membered heteroaryl having 1 to 3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur; Each R 3 These are hydrogen, deuterium, halogen, -CN, -NO2, -OR, -NR2, -SR, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NR(OR), -OC(O)R, -OC(O)NR2, -OP(O)(OR)2, -OP(O)(NR2)2, -OP(O)(OR)NR2, -N(R) Selected from C(O)R, -N(R)C(O)OR, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)S(O)2NR2, -N(R)P(O)(OR)2, -N(R)P(O)(OR)NR2, -P(O)(OR)2, -P(O)(NR2)OR, -P(O)(NR2)2, -Si(OH)2R, -Si(OH)(R)2, or -Si(R)3; Each R 4 C1~6 A optionally substituted group selected from aliphatic, phenyl, boron, nitrogen, oxygen, silicon, and sulfur-independently saturated or partially unsaturated heterocyclic rings of 4 to 7 members having 1 to 2 heteroatoms, and 5 to 6 members having 1 to 4 heteroatoms, independently selected from nitrogen, oxygen, and sulfur; R 5 This consists of hydrogen, deutherium, and optionally substituted C. 1~4 It is aliphatic or -CN; L is a covalent or divalent, saturated or unsaturated, linear or branched C 1~50 It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of -Cy-, -O-, -N(R)-, -Si(R)2-, -Si(OH)(R)-, -Si(OH)2-, -P(O)(OR)-, -P(O)(R)-, -P(O)(NR2)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by, here: Each -Cy- independently comprises phenylenyl, 8- to 10-membered bicyclic aryrenyl, 3- to 8-membered saturated or partially unsaturated carbocyclilenyl, 6- to 11-membered saturated or partially unsaturated spirocarbocyclilenyl, 5- to 12-membered, bridged or unbridged, bicyclic saturated or partially unsaturated carbocyclilenyl, 4- to 10-membered saturated or partially unsaturated heterocyclilenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, and 6- to 11-membered saturated cyclilenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur. Alternatively, a substituted divalent ring, optionally selected from a partially unsaturated spiroheterocrylenyl, a 5- to 12-membered bridged or unbridged bicyclic saturated or partially unsaturated heterocyclenyl, a 5- to 6-membered heteroarylenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, or an 8- to 10-membered bicyclic heteroarylenyl having 1 to 5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur; TBM is the target binding site; m is 0, 1, or 2; n is 0, 1, 2, 3, or 4; p is either 0 or 1, and if p is 0, the bond connecting ring A and ring B is: [ka] It is connected; Each of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and Each R is independently a hydrogen atom or a optionally substituted group, and this optionally substituted group is C 1~6 A 4- to 7-membered saturated or partially unsaturated heterocyclic compound having one or two heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur. Furthermore, it is selected from a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same nitrogen atom, together with the atom between them, form a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to this nitrogen atom.

[0030] In a particular embodiment, the present invention relates to formula II-B: [ka] The compound or a pharmaceutically acceptable salt thereof is provided, in formula II-B: X 1 These are covalent bonds, -CH2-, -C(O)-, -C(S)-, or [ka] It is the bivalent part selected from; R 1 C is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, or substituted as needed. 1~4 It is aliphatic; Ring A is, [ka] A monoring or biring ring selected from; Each R 2 These are independently hydrogen, -R 4 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Ring B is selected from a 6-membered aryl group containing 0 to 2 nitrogen atoms, or a 5-membered heteroaryl group containing 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Each R 3 These are independently hydrogen, -R 4 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Each R 4 C 1~6 A optionally substituted group selected from a 4- to 7-membered saturated or partially unsaturated heterocyclic ring having one or two heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered heteroaryl ring having one or four heteroatoms independently selected from nitrogen, oxygen, and sulfur; R 5 is hydrogen, C 1~4 It is aliphatic or -CN; L is a covalent or divalent, saturated or unsaturated, linear or branched C 1~50 It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of each other: -Cy-, -O-, -N(R)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by, here: Each -Cy- is independently a phenylenyl, an 8- to 10-membered bicyclic aryrenyl, a 4- to 7-membered saturated or partially unsaturated carbocyclilenyl, a 4- to 7-membered saturated or partially unsaturated spirocarbocyclilenyl, an 8- to 10-membered bicyclic saturated or partially unsaturated carbocyclilenyl, a 4- to 7-membered saturated or partially unsaturated heterocyclilenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 4- to 7-membered saturated cyclilenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur. A optionally substituted divalent ring selected from a summed or partially unsaturated spiroheterolenyl, an 8- to 10-membered bicyclic saturated or partially unsaturated heterocyclenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered heteroaryrenyl having one or four heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryrenyl having one or five heteroatoms independently selected from nitrogen, oxygen, or sulfur; TBM is the target binding site; m is 0, 1, or 2; n is 0, 1, 2, 3, or 4; p is either 0 or 1; Each of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and Each R is independently a hydrogen atom or a optionally substituted group, and this optionally substituted group is C 1~6 Selected from 4- to 7-membered saturated or partially unsaturated heterocyclic rings having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and 5- to 6-membered heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same nitrogen atom, together with the atom between them, form a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to this nitrogen atom.

[0031] In a particular embodiment, the present invention relates to formula II'-B: [ka] The compound or a pharmaceutically acceptable salt thereof is provided, in formula II'-B: X 1 These are covalent bonds, -CH2-, -C(O)-, -C(S)-, or [ka] It is the bivalent part selected from; R 1 C is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, or substituted as needed. 1~4 It is aliphatic; Ring A is, [ka] A monoring or biring ring selected from; Each R 2 These are independently hydrogen, -R 4 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Ring B is selected from a 6-membered aryl group containing 0 to 2 nitrogen atoms, or a 5-membered heteroaryl group containing 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Each R 3 These are independently hydrogen, -R 4, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Each R 4 C 1~6 A optionally substituted group selected from a 4- to 7-membered saturated or partially unsaturated heterocyclic ring having one or two heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered heteroaryl ring having one or four heteroatoms independently selected from nitrogen, oxygen, and sulfur; R 5 is hydrogen, C 1~4 It is aliphatic or -CN; L is a covalent or divalent, saturated or unsaturated, linear or branched C 1~50 It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of each other: -Cy-, -O-, -N(R)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by, here: Each -Cy- is independently a phenylenyl, an 8- to 10-membered bicyclic aryrenyl, a 4- to 7-membered saturated or partially unsaturated carbocyclilenyl, a 4- to 7-membered saturated or partially unsaturated spirocarbocyclilenyl, an 8- to 10-membered bicyclic saturated or partially unsaturated carbocyclilenyl, a 4- to 7-membered saturated or partially unsaturated heterocyclilenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 4- to 7-membered saturated cyclilenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur. A optionally substituted divalent ring selected from a summed or partially unsaturated spiroheterolenyl, an 8- to 10-membered bicyclic saturated or partially unsaturated heterocyclenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered heteroaryrenyl having one or four heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryrenyl having one or five heteroatoms independently selected from nitrogen, oxygen, or sulfur; TBM is the target binding site; m is 0, 1, or 2; n is 0, 1, 2, 3, or 4; p is either 0 or 1; Each of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and Each R is independently a hydrogen atom or a optionally substituted group, and this optionally substituted group is C 1~6 Selected from 4- to 7-membered saturated or partially unsaturated heterocyclic rings having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and 5- to 6-membered heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same nitrogen atom, together with the atom between them, form a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to this nitrogen atom.

[0032] In a particular embodiment, the present invention relates to formula II''-B: [ka] The compound or a pharmaceutically acceptable salt thereof is provided, in formula II''-B: X 1 These are covalent bonds, -C(R)2-, -C(O)-, -C(S)-, -P(O)(OR)-, -P(O)(R)-, -P(O)(NR2)-, -S(O)-, -S(O)2-, or [ka] It is the bivalent part selected from; X 2 is a carbon or silicon atom; X 3 is a divalent part selected from -C(R)2-, -N(R)-, -CF2-, -CHF-, -S-, or -O-; X 4 is a divalent part selected from a covalent bond or -C(R)2-; [ka] It is either a single bond or a double bond; R 1 This includes hydrogen, deuterium, halogens, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, -P(O)(OR)2, -P(O)(NR2)OR, -P(O)(NR2)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, and substituted C as needed. 1~4 It is aliphatic, or: R 1 and X 1 or X 4 These atoms, together with the atoms in between, form a 5- to 7-membered saturated, partially unsaturated carbocyclic ring, or a heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Ring A is, [ka] A monoring or biring ring selected from; Each R 2 These are independently hydrogen, deutherium, and -R 6 , halogen, -CN, -NO2, -OR, -SR, -NR2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, - OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)S(O)2NR2, -P(O)(OR)2, -P(O)(NR2)OR, or -P(O)(NR2)2; Ring B is selected from a 6-membered aryl group containing 0 to 3 nitrogen atoms, or a 5-membered heteroaryl group containing 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Each R 3 These are hydrogen, deuterium, halogen, -CN, -NO2, -OR, -NR2, -SR, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NR(OR), -OC(O)R, -OC(O)NR2, -OP(O)(OR)2, -OP(O)(NR2)2, -OP(O)(OR)NR2, -N(R) Selected from C(O)R, -N(R)C(O)OR, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)S(O)2NR2, -N(R)P(O)(OR)2, -N(R)P(O)(OR)NR2, -P(O)(OR)2, -P(O)(NR2)OR, -P(O)(NR2)2, -Si(OH)2R, -Si(OH)(R)2, or -Si(R)3; Each R 4 C 1~6 A optionally substituted group selected from aliphatic, phenyl, boron, nitrogen, oxygen, silicon, or sulfur-independently saturated or partially unsaturated heterocyclic rings of 4 to 7 members having 1 to 3 heteroatoms, and 5 to 6 members having 1 to 4 heteroatoms, independently selected from nitrogen, oxygen, and sulfur; R 5 This consists of hydrogen, deutherium, and optionally substituted C. 1~4 Aliphatic, or -C N is; L is a covalent or divalent, saturated or unsaturated, linear or branched C 1~50 It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of -Cy-, -O-, -N(R)-, -Si(R)2-, -Si(OH)(R)-, -Si(OH)2-, -P(O)(OR)-, -P(O)(R)-, -P(O)(NR2)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by, here: Each -Cy- independently comprises phenylenyl, 8- to 10-membered bicyclic aryrenyl, 3- to 8-membered saturated or partially unsaturated carbocyclilenyl, 6- to 11-membered saturated or partially unsaturated spirocarbocyclilenyl, 5- to 12-membered, bridged or unbridged, bicyclic saturated or partially unsaturated carbocyclilenyl, 4- to 10-membered saturated or partially unsaturated heterocyclilenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, and 6- to 11-membered saturated cyclilenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur. Alternatively, a substituted divalent ring, optionally selected from a partially unsaturated spiroheterocrylenyl, a 5- to 12-membered bridged or unbridged bicyclic saturated or partially unsaturated heterocyclenyl, a 5- to 6-membered heteroarylenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, or an 8- to 10-membered bicyclic heteroarylenyl having 1 to 5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur; TBM is the target binding site; m is 0, 1, or 2; n is 0, 1, 2, 3, or 4; p is either 0 or 1; Each of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and Each R is independently a hydrogen, deuterium, or optionally substituted group, and this optionally substituted group is C 1~6 Selected from 4- to 7-membered saturated or partially unsaturated heterocyclic rings having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and 5- to 6-membered heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same nitrogen atom, together with the atom between them, form a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to this nitrogen atom.

[0033] [ka] If the bonding point is shown on ring A, [ka] It is assumed that the bonding site can be any available carbon or nitrogen atom on ring A, and this will be understood by those skilled in the art. [ka] However, R 3 or R 5 When bonded to a nitrogen atom, R 3 or R 5 It does not exist, and [ka] However, R 3 Base or R 5 To replace the basis.

[0034] In certain embodiments, the present invention relates to formula III-A, III-B, or III-C: [ka] The compound or a pharmaceutically acceptable salt thereof is provided, in formulas III-A, III-B, and III-C, L and TBM are as defined above and described herein, and variable R 1 , R 2 , R 4 , R 5 , R 10 , R 11 , R 14 , R 17 , W 1 , W2 Each of X and n is a WO, which is incorporated herein by reference in whole. As defined in 2017 / 197051, and [ka] R 1 , R 1 and R 2 A ring formed by combining and, or R as defined in WO 2017 / 197051. 12 R at the binding site 17 It is coupled, and as a result, [ka] However, R 12 It replaces a substituent.

[0035] 2. Compounds and Definitions: The compounds of the present invention generally include those described above, and are further illustrated by the classes, subclasses, and species disclosed herein. Where used herein, unless otherwise specified, the following definitions apply. For the purposes of this invention, chemical elements are identified according to the periodic table, CAS versions, and Handbook of Chemistry and Physics, 75th edition. Furthermore, general principles of organic chemistry are also applied. The entire content of "Organic Chemistry," by Thomas Sorrell, University Science, is incorporated herein by reference. This information is found in Books, Sausalito: 1999, and in "March's Advanced Organic Chemistry," 5th edition, edited by Smith, M.B. and March, J., John Wiley & Sons, New York: 2001.

[0036] The terms “aliphatic” or “aliphatic group,” as used herein, mean a linear (i.e., unbranched) or branched, substituted or unsubstituted hydrocarbon chain containing one or more fully saturated or unsaturated units, or a monocyclic or bicyclic hydrocarbon (also referred herein as “carbocyclic,” “alicyclic,” or “cycloalkyl”) that is fully saturated or contains one or more unsaturated units but is not aromatic, and has one bond site to the remainder of the molecule. Unless otherwise specified, an aliphatic group contains one to six aliphatic carbon atoms. In some embodiments, an aliphatic group contains one to five aliphatic carbon atoms. In other embodiments, an aliphatic group contains one to four aliphatic carbon atoms. In yet another embodiment, an aliphatic group contains one to three aliphatic carbon atoms, and in yet another embodiment, an aliphatic group contains one to two aliphatic carbon atoms. In some embodiments, “alicyclic” (or “carbocyclic” or “cycloalkyl”) refers to a monocyclic C3-C6 hydrocarbon that is fully saturated or contains one or more unsaturated units, is not aromatic, and has one bond site to the remainder of the molecule. Suitable aliphatic groups include, but are not limited to, linear or branched, saturated or unsaturated alkyl groups, alkenyl groups, alkynyl groups, and hybrids thereof (e.g., (cycloalkyl)alkyl, (cycloalkenyl)alkyl, or (cycloalkyl)alkenyl).

[0037] As used herein, the term “bridged bicyclic” means any bicyclic ring system (i.e., carbocyclic or heterocyclic) having at least one bridge, whether saturated or partially unsaturated. As defined by IUPAC, a “bridge” is a multi-atom unbranched chain, or a single atom, or a valence bond connecting two bridgeheads, where “bridgehead” is any skeletal atom of the ring system bonded to three or more skeletal atoms (other than hydrogen). In some embodiments, a bridged bicyclic group has 7 to 12 ring members and 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Such bridged bicyclic groups are well known in the art and include the groups described below, where each group is bonded to the remainder of the molecule at any suitable carbon or nitrogen atom. Unless otherwise specified, bridged bicyclic groups are optionally substituted with one or more substituents, as described for aliphatic groups. In addition, or alternatively, any substitutable nitrogen of a bridged bicyclic group is optionally substituted. An example of a bridged double-ring type is: [ka] These are some examples.

[0038] The term "lower alkyl" refers to C 1~4 This refers to linear or branched alkyl groups. Exemplary lower alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tert-butyl.

[0039] The term "lower haloalkyl" refers to a C atom that is substituted with one or more halogen atoms. 1~4 This refers to a linear or branched alkyl group.

[0040] The term "heteroatom" refers to oxygen, sulfur, nitrogen, phosphorus, or silicon (any oxidation form of nitrogen, sulfur, phosphorus, or silicon; any quaternary form of basic nitrogen; or a substituteable nitrogen in a heterocyclic ring (e.g., N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl), or NR) +This means one or more of the following (including, for example, in N-substituted pyrrolidinyls).

[0041] The term "unsaturated," as used herein, means a portion having one or more unsaturated units.

[0042] As used herein, the term "divalent C 1~8 (or C 1~6 "Saturated or unsaturated, straight or branched hydrocarbon chains" means straight or branched, divalent alkylene, alkenylene, and alkynylene chains as defined herein.

[0043] The term "alkylene" refers to a divalent alkyl group. An "alkylene chain" is a polymethylene group, i.e., -(CH2) n - where n is a positive integer, preferably 1-6, 1-4, 1-3, 1-2, or 2-3. A substituted alkylene chain is a polymethylene group in which one or more methylene hydrogens are replaced by substituents. Suitable substituents include those listed below for substituted aliphatic groups.

[0044] The term "alkenylene" refers to a divalent alkenyl group. A substituted alkenylene chain is a polymethylene group containing at least one double bond and in which one or more hydrogen atoms are replaced by substituents. Suitable substituents include the substituted aliphatic groups listed below.

[0045] As used herein, the term "cyclopropyrenyl" refers to the following structure: [ka] This refers to the divalent cyclopropyl group.

[0046] The term "halogen" refers to F, Cl, Br, or I.

[0047] The term “aryl,” used alone or as part of a larger term such as “aralkyl,” “aralkoxy,” or “aryloxyalkyl,” means a monocyclic or bicyclic ring system having a total of 5 to 14 ring members, with at least one ring in the system being aromatic, and each ring in the system containing 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” means an aromatic ring system, including, but not limited to, phenyl, biphenyl, naphthyl, and anthracyl, which may have one or more substituents. Where the term “term” is used herein, and within its scope, it refers to a group in which an aromatic ring is condensed with one or more non-aromatic rings (e.g., indanyl, phthalimidyl, naphthoimidyl, phenantridinyl, or tetrahydronaphthyl).

[0048] The terms “heteroaryl” and “heteroaryl,” used alone or as part of a larger term (e.g., “heteroarylkyl” or “heteroaralkoxy”), mean a group having 5 to 10 ring atoms, preferably 5, 6, or 9 ring atoms; 6, 10, or 14 π electrons shared in a cyclic configuration; and 1 to 5 heteroatoms in addition to carbon atoms. The term “heteroatom” means nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur, and any quaternized form of basic nitrogen. Examples of heteroaryl groups include, but are not limited to, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridadinyl, pyrimidinyl, pyrazinyl, indolidinyl, prinyl, naphthilidinyl, and pteridinyl. The terms “heteroaryl” and “hetero-arra-” also, as used herein, encompass groups in which a heteroaromatic ring is fused to one or more aryl, alicyclic, or heterocyclic rings, and whose radical or bond site lies on the heteroaromatic ring. Non-limiting examples include indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzothiazolyl, quinolyl, isoquinolyl, sinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H-quinolidinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and pyrido[2,3-b]-1,4-oxazine-3(4H)-one. Heteroaryl groups may be monocyclic or bicyclic. The term "heteroaryl" may be used interchangeably with the terms "heteroaryl ring," "heteroaryl group," or "heteroaromatic," any of which may include a ring that is substituted as needed. The term "heteroaralkyl" refers to an alkyl group substituted with a heteroaryl group, where the alkyl and heteroaryl parts are considered independently and as needed. It is being replaced accordingly.

[0049] As used herein, the terms “heterocyclic,” “heterocyclyl,” “heterocyclic radical,” and “heterocyclic ring” are interchangeable and stable 5- to 7-membered monocyclic or 7- to 10-membered bicyclic rings, which are either saturated or partially unsaturated and have one or more, preferably 1 to 4, heteroatoms in addition to the carbon atoms, as defined above. As used in reference to the ring atoms of a heterocyclic ring, the term “nitrogen” includes substituted nitrogen. For example, in a saturated or partially unsaturated ring having 0 to 3 heteroatoms selected from oxygen, sulfur, or nitrogen, the nitrogen may be N (as in 3,4-dihydro-2H-pyrrolyl) or NH (as in pyrrolidinyl), + It may also be NR (as in N-substituted pyrrolidinyl).

[0050] Heterocyclic rings can be bonded to their parent group at any heteroatom or carbon atom that results in a stable structure, and any of these ring atoms can be substituted as needed. Examples of such saturated or partially unsaturated heterocyclic radicals include, but are not limited to, tetrahydrofuranyl, tetrahydrothiophenylpyrrolidinyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, 2-oxa-6-azaspiro[3.3]heptane, and quinuclidinyl. The terms “heterocyclic,” “heterocyclyl,” “heterocyclyl ring,” “heterocyclic group,” “heterocyclic moiety,” and “heterocyclic radical” are interchangeable herein and also encompass groups in which the heterocyclyl ring is fused to one or more aryl rings, heteroaryl rings, or alicyclic rings (e.g., indolinyl, 3H-indolyl, chromanyl, phenantridinyl, or tetrahydroquinolinyl). The heterocyclyl group may be monocyclic or bicyclic. The term “heterocyclylalkyl” means an alkyl group substituted with a heterocyclyl, where the alkyl moiety and the heterocyclyl moiety are substituted independently as needed.

[0051] As used herein, the term “partially unsaturated” means a ring portion containing at least one double or triple bond. The term “partially unsaturated” is intended to encompass rings having multiple unsaturated sites, but not to encompass aryl or heteroaryl moies as defined herein.

[0052] As described herein, the compounds of the present invention may include “optionally substituted” moieties. Generally, the term “substituted” means that one or more hydrogens of a designated moiety are replaced with appropriate substituents, whether preceded or not by the term “optionally”. Unless otherwise indicated, an “optionally substituted” group may have appropriate substituents on each of its substituted moieties, and if one or more positions in any given structure can be replaced with one or more substituents selected from a particular group, the substituents may be the same or different at each position. The substituent combinations envisioned by the present invention are preferably combinations that result in the formation of stable compounds or chemically possible compounds. The term “stable,” as used herein, means a compound that remains substantially unchanged when produced, detected, and, in particular embodiments, subjected to conditions that enable their recovery, purification, and use for one or more of the purposes disclosed herein.

[0053] A suitable monovalent substituent on the substitutable carbon atom of the "substituted as needed" group is, independently, a halogen;-(CH2) 0~4 R ○ ;-(CH2) 0~4 Ure ○ ;-O(CH2)0 ~4 R ○ -O-(CH2) 0~4 C(O)OR ○ ;-(CH2) 0~4 CH(OR ○ )2;-(CH2) 0~4 SR ○ ;-(CH2) 0~4 Ph (This is R ○ It can be replaced by (CH2) 0~4 O(CH2) 0~1 Ph (This is R ○ It can be substituted with);-CH=CHPh(this is R ○ It can be replaced by (CH2) 0~4 O(CH2) 0~1 -Pyridyl (This is R○ which may be replaced by; -NO2; -CN; -N3; -(CH2) 0~4 N(R ○ )2; -(CH2) 0~4 N(R ○ )C(O)R ○ ; -N(R ○ )C(S)R ○ ; -(CH2) 0~4 N(R ○ )C(O)NR ○ 2; -N(R ○ )C(S)NR ○ 2; -(CH2) 0~4 N(R ○ )C(O)OR ○ ; -N(R ○ )N(R ○ )C(O)R ○ ; -N(R ○ )N(R ○ )C(O)NR ○ 2; -N(R ○ )N(R ○ )C(O)OR ○ ; -(CH2) 0~4 C(O)R ○ ; -C(S)R ○ ; -(CH2) 0~4 C(O)OR ○ ; -(CH2) 0~4 C(O)SR ○ ; -(CH2) 0~4 C(O)OSiR ○ 3; -(CH2) 0~4 OC(O)R ○ ; -OC(O)(CH2) 0~4 SR ○ ; -SC(S)SR ○ ; -(CH2) 0~4 SC(O)R ○ ; -(CH2) 0~4 C(O)NR ○ 2; -C(S)NR ○ 2; -C(S)SR ○ ; -(CH2) 0~4 OC(O)NR ○ 2; -C(O)N(OR ○ )R ○ ; -C(O)C(O)R ○ ; -C(O)CH2C(O)R○ ;-C(NOR ○ )R ○ ;-(CH2) 0~4 SSR ○ ;-(CH2) 0~4 S(O)2R ○ ;-(CH2) 0~4 S(O)2OR ○ ;-(CH2) 0~4 OS(O)2R ○ ;-S(O)2NR ○ 2;-(CH2) 0~4 S(O)R ○ ;-N(R ○ )S(O)2NR ○ 2;-N(R ○ )S(O)2R ○ ;-N(OR ○ )R ○ ;-C(NH)NR ○ 2;-P(O)2R ○ ;-P(O)R ○ 2;-OP(O)R ○ 2;-OP(O)(OR ○ )2;-SiR ○ 3;-(C 1~4 (Linear or branched alkylene) ON(R ○ )2; or -(C 1~4 (Linear or branched alkylene)C(O)ON(R ○ )2, where each R ○ These can be substituted as defined below, and independently, hydrogen, C 1~6 Aliphatic, -CH2Ph, -O(CH2) 0~1 Ph, -CH2- (a 5- to 6-membered heteroaryl ring), or a 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or notwithstanding the above definition, R ○ Two independent entities of these, together with an atom(s) between them, form a 3- to 12-membered saturated, partially unsaturated, or aryl monocyclic or bicyclic ring, each containing 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which can be substituted as defined below.

[0054] R ○ (R ○ The appropriate monovalent substituents on the ring formed by the two independent entities of these atoms joining together with the atom between them are halogens, -(CH2) 0~2 R ● ,-(HaroR ● ), -(CH2) 0~2 OH, -(CH2) 0~2 Ure ● ,-(CH2) 0~2 CH(OR ● )2;-O(HaroR ● ), -CN, -N3, -(CH2) 0~2 C(O)R ● ,-(CH2) 0~2 C(O)OH, -(CH2) 0~2 C(O)OR ● ,-(CH2) 0~2 SR ● ,-(CH2) 0~2 SH, -(CH2) 0~2 NH2, -(CH2) 0~2 NHR ● ,-(CH2) 0~2 NR ● 2, -NO2, -SiR ● 3. -OSiR ● 3. -C(O)SR ● ,-(C 1~4 (Straight-chain or branched alkylene)C(O)OR ● , or -SSR ● And here each R ● It is either not substituted, or if preceded by "halo", it is substituted by only one or more halogens, and independently, C 1~4 Aliphatic, -CH2Ph, -O(CH2) 0~1 Ph, or selected from 5- to 6-membered saturated, partially unsaturated, or aryl rings having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. ○ Suitable divalent substituents on the saturated carbon atom include =O and =S.

[0055] Suitable divalent substituents on the saturated carbon atoms of the "substituted as needed" groups include: =O, =S, =NNR * 2. =NNHC(O)R * 、=NNHC(O)OR * ,=NNHS(O)2R * ,=NR * 、=NOR * , -O(C(R * 2)) 2~3 O-, or -S(C(R * 2)) 2~3 S-. Here's R * Each independent entity is hydrogen C which can be replaced as defined below 1~6 Selected from aliphatic, or unsubstituted 5- to 6-membered saturated, partially unsaturated, or aryl rings having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents bonded to the substituteable carbon of the vicinal of the "optionally substituted" group include -O(CR * 2) 2~3 O- is mentioned, and here R * Each independent entity is a hydrogen, which can be substituted as defined below. 1~6 Selected from aliphatic or unsubstituted 5- to 6-membered saturated, partially unsaturated, or aryl rings having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0056] R * Suitable substituents on the aliphatic group include halogens, -R ● ,-(HaroR ● ), -OH, -OR ● ,-O(HaroR ● ), -CN, -C(O)OH, -C(O)OR ● -NH2, -NHR ● , -NR ● 2, or -NO2, where each R ● It is either not substituted, or if preceded by "halo", it is substituted by only one or more halogens, and independently, C 1~4 Aliphatic, -CH2Ph, -O(CH2)0~1 It is a 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms, or independently selected from nitrogen, oxygen, or sulfur.

[0057] A suitable substitutionable substituent on the nitrogen of the "substituted as needed" group is -R † , -NR † 2, -C(O)R † , -C(O)OR † ,-C(O)C(O)R † -C(O)CH2C(O)R † -S(O)2R † -S(O)2NR † 2, -C(S)NR † 2, -C(NH)NR † 2, or -N(R † )S(O)2R † These are listed; here each R † C can be substituted independently of hydrogen, as defined below. 1~6 Aliphatic, unsubstituted -OPh, or an unsubstituted 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or notwithstanding the above definition, R † Two independent entities of these elements, together with an atom(s) between them, form an unsubstituted 3- to 12-membered saturated, partially unsaturated, or aryl monocyclic or bicyclic ring, each containing 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0058] R † Suitable substituents on the aliphatic group are, independently, halogens, -R ● ,-(HaroR ● ), -OH, -OR ● ,-O(HaroR ● ), -CN, -C(O)OH, -C(O)OR ● -NH2, -NHR ● , -NR ● 2, or -NO2, where each R ●It is either not substituted, or if preceded by "halo", it is substituted by only one or more halogens, and independently, C 1~4 Aliphatic, -CH2Ph, -O(CH2) 0~1 It is a 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms, or independently selected from nitrogen, oxygen, or sulfur.

[0059] As used herein, the term “pharmaceutically acceptable salt” means a salt that, within reasonable medical judgment, is appropriate for use in contact with human and lower animal tissues without excessive toxicity, irritation, and allergic reactions, and that is balanced by a reasonable benefit / risk ratio. pharmaceutically acceptable salts are well known in the art. For example, SMBerge et al., in J. Pharmaceutical Sciences, 1977, 66, 1-19, describe pharmaceutically acceptable salts in detail, which are incorporated herein by reference. Examples of pharmaceutically acceptable salts of the compounds of the present invention include salts derived from suitable inorganic acids, inorganic bases, organic acids, and organic bases. Examples of pharmaceutically acceptable, non-toxic acid addition salts are salts of amino groups formed with inorganic acids (e.g., hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid) or organic acids (e.g., acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid), or by other methods used in the field, such as ion exchange. Other pharmaceutically acceptable salts include adipines, alginates, ascorbic acid, and asparagus. Laginate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphor sulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptoneate, glycerophosphate, gluconate, hemisulfate, heptaneate, hexanoate, hydroiodide, 2-hydroxyethanesulfonate, lactobionate, lactate, laurin Examples include salts, 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, and valerate.

[0060] Examples of salts derived from suitable bases include alkali metal salts, alkaline earth metal salts, ammonium salts, and N + (C 1~4 Examples include alkyl)4 salts. Typical alkali metal salts or alkaline earth metal salts include sodium, lithium, potassium, calcium, and magnesium. Further pharmaceutically acceptable salts, where appropriate, include non-toxic ammonium, quaternary ammonium, and amine cations formed with counterions such as halide ions, hydroxide ions, carbonate ions, sulfate ions, phosphate ions, nitrate ions, lower alkyl sulfonate ions, and aryl sulfonate ions.

[0061] Unless otherwise stated, the structures illustrated herein also mean that all isomers (e.g., enantiomers, diastereomers, and geometric (or conformational) forms) of that structure, such as the R and S configurations for each chiral center, the Z and E double bond isomers, and the Z and E conformational isomers. Thus, single stereochemical isomers of the compounds of the present invention, as well as enantiomers, diastereomers, and geometric (or conformational) mixtures, are within the scope of the present invention. Unless otherwise stated, all tautomer forms of the compounds of the present invention are within the scope of the present invention. Furthermore, unless otherwise stated, the structures illustrated herein also mean that all compounds differ only in the presence of one or more isotope-enriched atoms. For example, the structures of the present invention in which hydrogen is replaced by deuterium or tritium, or carbon 13 C or 14 Compounds having the present invention in which C is replaced with enriched carbon are within the scope of the present invention. Such compounds are useful, for example, as analytical tools according to the present invention, as probes in biological assays, or as therapeutic agents. In certain embodiments, the provided compounds may be substituted with one or more deuterium atoms.

[0062] As used herein, the terms “binding agent” or “inhibitor” are defined as compounds that bind to CRBN and bind or inhibit the targeted protein with measurable affinity. In certain embodiments, the inhibitor is an IC of less than about 50 μM, less than about 1 μM, less than about 500 nM, less than about 100 nM, less than about 10 nM, or less than about 1 nM. 50 It has and / or coupling constants.

[0063] The compounds of the present invention can be anchored to a detectable moiety. It is understood that such compounds are useful as imaging agents. Those skilled in the art will recognize that the detectable moiety may be bonded to the provided compound via a suitable substituent. In this specification, the term “suitable substituent” means a moiety that can be covalently bonded to the detectable moiety. Such moieties are well known to those skilled in the art and include, for example, groups containing a carbonate moiety, an amino moiety, a thiol moiety, or a hydroxyl moiety. It is understood that such moieties may be bonded directly to the provided compound or via a anchoring group such as a divalent saturated or unsaturated hydrocarbon chain. In some embodiments, such moieties are The components can be bonded by click chemistry. In some embodiments, such components can be bonded by 1,3-cycloaddition of an azide with an alkyne, if necessary, in the presence of a copper catalyst. Methods using click chemistry are known in the art and are described by Rostovtsev et al., Angew. Chem. Int. Ed. 2002, 41, 2596-99 and Sun et al., Bioconjugate Chem., 2006, 17, 52-57.

[0064] In this specification, the term “detectable portion” is used interchangeably with the term “label” and refers to any portion that can be detected, e.g., primary and secondary labels. Radioactive isotopes (e.g., tritium, 32 P, 33 P, 35 S, or 14 C) Primary labels such as mass tags and fluorescent labels are signal-generating reporter groups that can be detected without further modification. Other detectable parts include luminescent groups and phosphorescent groups.

[0065] In this specification, the term “secondary label” refers to a portion of a protein, such as biotin and various protein antigens, that requires the presence of a secondary intermediate to generate a detectable signal. For biotin, the secondary intermediate may include a streptavidin-enzyme conjugate. For antigen labeling, the secondary intermediate may include an antibody-enzyme conjugate. Some fluorescent groups act as secondary labels because they transfer energy to another group in a non-radioactive fluorescence resonance energy transfer (FRET) process, producing a signal in which the second group is detectable.

[0066] In this specification, the terms "fluorescent label," "fluorescent dye," and "fluorescent phosphone" refer to a portion that absorbs light energy at a specified excitation wavelength and emits light energy at a different wavelength. Examples of fluorescent labels include Alexa Fluor dyes (Alexa Fluor350, Alexa Fluor488, Alexa Fluor532, Alexa Fluor546, Alexa Fluor568, Alexa Fluor594, Alexa Fluor633, Alexa Fluor660, and Alexa Fluor680), AMCA, AMCA-S, and BODIPY dyes (BODIPY FL, BODIPY R6G, BODIPY TMR, BODIPY TR, BODIPY530 / 550, BODIPY558 / 568, BODIPY564 / 570, BODIPY576 / 589, BODIPY581 / 591, BODIPY630 / 650, BODIPY650 / 665), Carboxyrhodamine 6G, Carboxy-X-Rhodamine (ROX), Cascade Blue, Cascade Yellow, Coumarin 343, Cyanine dye (Cy3, Cy5, Cy3.5, Cy5.5), Dansyl, Dapoxyl, Dialkylaminocoumarin, 4',5'-Dichloro-2',7'-Dimethoxy-Fluorescein, DM-NERF, Eosin, Erythrosine, Fluorescein, FAM, Hid Examples include, but are not limited to, roxycoumarin, IRDyes (IRD40, IRD700, IRD800), JOE, Lisamin 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, and Texas Red-X.

[0067] In this specification, the term “mass tag” means any portion that can be uniquely detected by its mass using mass spectrometry (MS) detection techniques. Examples of mass tags include electrophore-emitting tags such as N-[3-[4'-[(p-methoxytetrafluorobenzyl)oxy]phenyl]-3-methylglyceronyl]isonipeconate, 4'-[2,3,5,6-tetrafluoro-4-(pentafluorophenoxyl)]methylacetophenone and their derivatives. The synthesis and utility of these mass tags are described in U.S. Patents 4,650,750, 4,709,016, 5,360,8191, and 5,516. This is described in publications 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, oligopeptides, oligosaccharides, and other synthetic polymers of various lengths and monomer compositions. A wide variety of organic molecules (biomolecules or synthetic compounds), both neutral and charged, within a suitable mass range (100 to 2000 daltons) may be used as mass tags.

[0068] The terms “measurable affinity” and “measurably adjustable” mean, as used herein, a measurable change in CRBN activity between a sample containing the compound or its composition and CRBN of the present invention and an equivalent sample containing CRBN in which neither the compound nor its composition exists.

[0069] 3. Description of exemplary embodiments: As described above, in a particular embodiment, the present invention relates to formula I: [ka] Provides a compound or a pharmaceutically acceptable salt thereof, in formula I: X 1 These are covalent bonds, -CH2-, -C(O)-, -C(S)-, or [ka] It is the bivalent part selected from; R 1 C is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, or substituted as needed. 1~4 It is aliphatic; Each R 2 These are independently hydrogen, -R 6 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Ring A is, [ka] A biring or triring ring selected from, where Ring B is a fused ring selected from a 6-membered aryl containing 0 to 2 nitrogen atoms, a 5- to 7-membered partially saturated carbocyclyl, a 5- to 7-membered partially saturated heterocyclyl having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5-membered heteroaryl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 3 This is selected from hydrogen, halogen, -OR, -N(R)2, or -SR; Each R 4 These are independently hydrogen, -R 6 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; R 5 is hydrogen, C 1~4 It is aliphatic or -CN; Each R 6 C 1~6 A optionally substituted group selected from a 4- to 7-membered saturated or partially unsaturated heterocyclic ring having one or two heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered heteroaryl ring having one or four heteroatoms independently selected from nitrogen, oxygen, and sulfur; L is a covalent or divalent, saturated or unsaturated, linear or branched C 1~50 It is a hydrocarbon chain, where the 0 to 6 methylene units of L are independently -Cy-, - O-, -N(R)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O) 2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by, here: Each -Cy- is independently a phenylenyl, an 8- to 10-membered bicyclic aryrenyl, a 4- to 7-membered saturated or partially unsaturated carbocyclilenyl, a 4- to 7-membered saturated or partially unsaturated spirocarbocyclilenyl, an 8- to 10-membered bicyclic saturated or partially unsaturated carbocyclilenyl, a 4- to 7-membered saturated or partially unsaturated heterocyclilenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 4- to 7-membered saturated cyclilenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur. A optionally substituted divalent ring selected from a summed or partially unsaturated spiroheterolenyl, an 8- to 10-membered bicyclic saturated or partially unsaturated heterocyclenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered heteroaryrenyl having one or four heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryrenyl having one or five heteroatoms independently selected from nitrogen, oxygen, or sulfur; TBM is the target binding site; m is 0, 1, 2, 3, or 4; Each of n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and Each R is independently a hydrogen atom or a optionally substituted group, and this optionally substituted group is C 1~6 Selected from 4- to 7-membered saturated or partially unsaturated heterocyclic rings having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and 5- to 6-membered heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same nitrogen atom, together with the atom between them, form a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to this nitrogen atom.

[0070] As described above, in a particular embodiment, the present invention relates to formula I': [ka] Provides a compound or a pharmaceutically acceptable salt thereof, in formula I': X 1 These are covalent bonds, -CH2-, -C(O)-, -C(S)-, or [ka] It is the bivalent part selected from; R 1 C is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, or substituted as needed. 1~4 It is aliphatic; Each R 2 These are independently hydrogen, -R 6, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Ring A is such that Ring B is not imidazo or benzo. [ka] , [ka] Ring B is not benzo. [ka] Ring B is not benzo. [ka] , [ka] Ring B is not benzo. [ka] [ka] A biring or triring ring selected from, where Ring B is a fused ring selected from a 6-membered aryl containing 0 to 2 nitrogen atoms, a 5- to 7-membered partially saturated carbocyclyl, a 5- to 7-membered partially saturated heterocyclyl having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5-membered heteroaryl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 3 This is selected from hydrogen, halogen, -OR, -N(R)2, or -SR; Each R 4 These are independently hydrogen, -R6 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O )NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or is -N(R)S(O)2R; R 5 is hydrogen, C 1~4 It is aliphatic or -CN; Each R 6 C 1~6 A optionally substituted group selected from a 4- to 7-membered saturated or partially unsaturated heterocyclic ring having one or two heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered heteroaryl ring having one or four heteroatoms independently selected from nitrogen, oxygen, and sulfur; L is a covalent or divalent, saturated or unsaturated, linear or branched C 1~50 It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of each other: -Cy-, -O-, -N(R)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by, here: Each -Cy- is independently a phenylenyl, an 8- to 10-membered bicyclic aryrenyl, a 4- to 7-membered saturated or partially unsaturated carbocyclilenyl, a 4- to 7-membered saturated or partially unsaturated spirocarbocyclilenyl, an 8- to 10-membered bicyclic saturated or partially unsaturated carbocyclilenyl, a 4- to 7-membered saturated or partially unsaturated heterocyclilenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 4- to 7-membered saturated cyclilenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur. A optionally substituted divalent ring selected from a summed or partially unsaturated spiroheterolenyl, an 8- to 10-membered bicyclic saturated or partially unsaturated heterocyclenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered heteroaryrenyl having one or four heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryrenyl having one or five heteroatoms independently selected from nitrogen, oxygen, or sulfur; TBM is the target binding site; m is 0, 1, 2, 3, or 4; Each of n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and Each R is independently a hydrogen atom or a optionally substituted group, and this optionally substituted group is C 1~6 Selected from 4- to 7-membered saturated or partially unsaturated heterocyclic rings having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and 5- to 6-membered heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same nitrogen atom, together with the atom between them, form a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to this nitrogen atom.

[0071] In a particular embodiment, the present invention relates to formula I'': [ka] Provides a compound or a pharmaceutically acceptable salt thereof, in formula I'': X 1 These are covalent bonds, -C(R)2-, -C(O)-, -C(S)-, -P(O)(OR)-, -P(O)(R)-, -P(O)(NR2)-, -S(O)-, -S(O)2-, or [ka] It is the bivalent part selected from; X 2 is a carbon or silicon atom; X 3 is a divalent part selected from -C(R)2-, -N(R)-, -CF2-, -CHF-, -S-, or -O-; X 4 is a divalent part selected from a covalent bond or -C(R)2-; [ka] It is either a single bond or a double bond; R 1 This includes hydrogen, deuterium, halogens, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, -P(O)(OR)2, -P(O)(NR2)OR, -P(O)(NR2)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, and substituted C as needed. 1~4 It is aliphatic, or: R 1 and X 1 or X 4 These atoms, together with the atoms in between, form a 5- to 7-membered saturated, partially unsaturated carbocyclic ring, or a heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Each R 2 These are independently hydrogen, deutherium, and -R 6, halogen, -CN, -NO2, -OR, -SR, -N(R)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR , -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)S(O)2NR2, -P(O)(OR)2, -P(O)(NR2)OR, or -P(O)NR2; Ring A is, [ka] A biring or triring ring selected from, where Ring B is a condensed ring selected from a 6-membered aryl containing 0 to 3 nitrogen atoms, a 5- to 7-membered partially saturated carbocyclyl, a 5- to 7-membered partially saturated heterocyclyl having 1 to 3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur, or a 5-membered heteroaryl having 1 to 3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur; R 3 These are hydrogen, deuterium, halogen, -CN, -NO2, -OR, -NR2, -SR, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NR(OR), -OC(O)R, -OC(O)NR2, -OP(O)(OR)2, -OP(O)(NR2)2, -OP(O)(OR)NR2, -N(R) Selected from C(O)R, -N(R)C(O)OR, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)S(O)2NR2, -N(R)P(O)(OR)2, -N(R)P(O)(OR)NR2, -P(O)(OR)2, -P(O)(NR2)OR, -P(O)(NR2)2, -Si(OH)2R, -Si(OH)(R)2, or -Si(R)3; Each R 4 These are independently hydrogen, deutherium, and -R 6, halogen, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -P(O)(OR)2, -P(O)(NR2)OR, or -P(O)(NR2)2; R 5 This consists of hydrogen, deutherium, and optionally substituted C. 1~4 Aliphatic, or -C N is; Each R 6 C 1~6 A optionally substituted group selected from aliphatic, phenyl, boron, nitrogen, oxygen, silicon, or sulfur-independently saturated or partially unsaturated heterocyclic rings of 4 to 7 members having 1 to 3 heteroatoms, and 5 to 6 membered heteroaryl rings having 1 to 4 heteroatoms, independently selected from boron, nitrogen, oxygen, silicon, or sulfur; L is a covalent or divalent, saturated or unsaturated, linear or branched C 1~50 It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of each other: -Cy-, -O-, -N(R)-, -Si(R)2-, -Si(OH)(R)-, -Si(OH)2-, -C(H)(CF3)-, -P(O)(OR)-, -P(O)(R)-, -P(O)(NR2)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by, here: Each -Cy- independently comprises phenylenyl, 8- to 10-membered bicyclic arylenyl, 4- to 8-membered saturated or partially unsaturated carbocyclilenyl, 6- to 11-membered saturated or partially unsaturated spirocarbocyclilenyl, 5- to 12-membered, bridged or unbridged, bicyclic saturated or partially unsaturated carbocyclilenyl, 4- to 10-membered saturated or partially unsaturated heterocyclilenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, and 6- to 11-membered saturated cyclilenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur. Alternatively, a substituted divalent ring, optionally selected from a partially unsaturated spiroheterocrylenyl, a 5- to 12-membered bridged or unbridged bicyclic saturated or partially unsaturated heterocyclenyl, a 5- to 6-membered heteroarylenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, or an 8- to 10-membered bicyclic heteroarylenyl having 1 to 5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur; TBM is the target binding site; m is 0, 1, 2, 3, or 4; Each of n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and Each R is independently a hydrogen atom or a optionally substituted group, and this optionally substituted group is C 1~6 Selected from 4- to 7-membered saturated or partially unsaturated heterocyclic rings having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and 5- to 6-membered heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same nitrogen atom, together with the atom between them, form a 4-membered system with 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to this nitrogen atom. They form saturated, partially unsaturated, or heteroaryl rings with approximately 7 members.

[0072] As described above, in a particular embodiment, the present invention relates to formula II-A: [ka] The compound or a pharmaceutically acceptable salt thereof is provided, in formula II-A: X 1 These are covalent bonds, -CH2-, -C(O)-, -C(S)-, or [ka] It is the bivalent part selected from; R 1 C is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, or substituted as needed. 1~4 It is aliphatic; Ring A is, [ka] A monoring or biring ring selected from; Each R 2 These are independently hydrogen, -R 4 Halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O )OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Ring B is selected from a 6-membered aryl group containing 0 to 2 nitrogen atoms, or a 5-membered heteroaryl group containing 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Each R 3 These are independently hydrogen, -R 4, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Each R 4 C 1~6 A optionally substituted group selected from a 4- to 7-membered saturated or partially unsaturated heterocyclic ring having one or two heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered heteroaryl ring having one or four heteroatoms independently selected from nitrogen, oxygen, and sulfur; R 5 is hydrogen, C 1~4 It is aliphatic or -CN; L is a covalent or divalent, saturated or unsaturated, linear or branched C 1~50 It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of each other: -Cy-, -O-, -N(R)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by, here: Each -Cy- is independently a phenylenyl, an 8- to 10-membered bicyclic aryrenyl, a 4- to 7-membered saturated or partially unsaturated carbocyclilenyl, a 4- to 7-membered saturated or partially unsaturated spirocarbocyclilenyl, an 8- to 10-membered bicyclic saturated or partially unsaturated carbocyclilenyl, a 4- to 7-membered saturated or partially unsaturated heterocyclilenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 4- to 7-membered saturated cyclilenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur. A optionally substituted divalent ring selected from a summed or partially unsaturated spiroheterolenyl, an 8- to 10-membered bicyclic saturated or partially unsaturated heterocyclenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered heteroaryrenyl having one or four heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryrenyl having one or five heteroatoms independently selected from nitrogen, oxygen, or sulfur; TBM is the target binding site; m is 0, 1, or 2; n is 0, 1, 2, 3, or 4; p is either 0 or 1, and if p is 0, the bond connecting ring A and ring B is: [ka] It is connected; Each of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and Each R is independently a hydrogen atom or a optionally substituted group, and this optionally substituted group is C 1~6 Selected from 4- to 7-membered saturated or partially unsaturated heterocyclic rings having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and 5- to 6-membered heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same nitrogen atom, together with the atom between them, form a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to this nitrogen atom.

[0073] As described above, in a particular embodiment, the present invention relates to formula II'-A: [ka] The compound or a pharmaceutically acceptable salt thereof is provided, in formula II'-A: X 1 These are covalent bonds, -CH2-, -C(O)-, -C(S)-, or [ka] It is the bivalent part selected from; R 1 C is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, or substituted as needed. 1~4 It is aliphatic; Ring A is, [ka] A monoring or biring ring selected from; Each R 2 These are independently hydrogen, -R 4 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Ring B is selected from a 6-membered aryl group containing 0 to 2 nitrogen atoms, or a 5-membered heteroaryl group containing 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Each R 3 These are independently hydrogen, -R 4, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Each R 4 C 1~6 A optionally substituted group selected from a 4- to 7-membered saturated or partially unsaturated heterocyclic ring having one or two heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered heteroaryl ring having one or four heteroatoms independently selected from nitrogen, oxygen, and sulfur; R 5 is hydrogen, C 1~4 It is aliphatic or -CN; L is a covalent or divalent, saturated or unsaturated, linear or branched C 1~50 It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of each other: -Cy-, -O-, -N(R)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by, here: Each -Cy- is independently a phenylenyl, an 8- to 10-membered bicyclic aryrenyl, a 4- to 7-membered saturated or partially unsaturated carbocyclilenyl, a 4- to 7-membered saturated or partially unsaturated spirocarbocyclilenyl, an 8- to 10-membered bicyclic saturated or partially unsaturated carbocyclilenyl, a 4- to 7-membered saturated or partially unsaturated heterocyclilenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 4- to 7-membered saturated cyclilenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur. A optionally substituted divalent ring selected from a summed or partially unsaturated spiroheterolenyl, an 8- to 10-membered bicyclic saturated or partially unsaturated heterocyclenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered heteroaryrenyl having one or four heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryrenyl having one or five heteroatoms independently selected from nitrogen, oxygen, or sulfur; TBM is the target binding site; m is 0, 1, or 2; n is 0, 1, 2, 3, or 4; p is either 0 or 1, and if p is 0, the bond connecting ring A and ring B is: [ka] It is connected; Each of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and Each R is independently a hydrogen atom or a optionally substituted group, and this optionally substituted group is C 1~6 Selected from 4- to 7-membered saturated or partially unsaturated heterocyclic rings having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and 5- to 6-membered heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same nitrogen atom, together with the atom between them, form a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to this nitrogen atom.

[0074] In a particular embodiment, the present invention relates to formula II''-A: [ka] The compound or a pharmaceutically acceptable salt thereof is provided, in formula II''-A: X 1 These are covalent bonds, -C(R)2-, -C(O)-, -C(S)-, -P(O)(OR)-, -P(O)(R)-, -P(O)(NR2)-, -S(O)-, -S(O)2-, or [ka] It is the bivalent part selected from; X 2 is a carbon or silicon atom; X 3 is a divalent part selected from -C(R)2-, -N(R)-, -CF2-, -CHF-, -S-, or -O-; X 4 is a divalent part selected from a covalent bond or -C(R)2-; [ka] It is either a single bond or a double bond; R 1 This includes hydrogen, deuterium, halogens, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, -P(O)(OR)2, -P(O)(NR2)OR, -P(O)(NR2)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, and substituted C as needed. 1~4 It is aliphatic, or: R 1 and X 1 or X 4These atoms, together with the atoms in between, form a 5- to 7-membered saturated, partially unsaturated carbocyclic ring, or a heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Ring A is, [ka] A monoring or biring ring selected from; Each R 2 These are independently hydrogen, deutherium, and -R 4 , halogen, -CN, -NO2, -OR, -SR, -N(R)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)S(O)2NR2, -P(O)(OR)2, -P(O)(NR2)OR, or -P(O)(NR2)2; Ring B is selected from a 6-membered aryl containing 0 to 3 nitrogen atoms, or a 5-membered heteroaryl having 1 to 3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur; Each R 3 is hydrogen, deutherium, -R 4 , halogen, -CN, -NO2, -OR, -NR2, -SR, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, - C(O)NR(OR), -OC(O)R, -OC(O)NR2, -OP(O)(OR)2, -OP(O)(NR2)2, -OP(O)(OR)NR2, -N(R)C(O)R, Selected from -N(R)C(O)OR, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)S(O)2NR2, -N(R)P(O)(OR)2, -N(R)P(O)(OR)NR2, -P(O)(OR)2, -P(O)(NR2)OR, -P(O)(NR2)2, -Si(OH)2R, -Si(OH)(R)2, or -Si(R)3; Each R 4C 1~6 A optionally substituted group selected from aliphatic, phenyl, boron, nitrogen, oxygen, silicon, or sulfur-independently saturated or partially unsaturated heterocyclic rings of 4 to 7 members having 1 to 3 heteroatoms, and 5 to 6 members having 1 to 4 heteroatoms, independently selected from nitrogen, oxygen, and sulfur; R 5 This consists of hydrogen, deutherium, and optionally substituted C. 1~4 It is aliphatic or -CN; L is a covalent or divalent, saturated or unsaturated, linear or branched C 1~50 It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of -Cy-, -O-, -N(R)-, -Si(R)2-, -Si(OH)(R)-, -Si(OH)2-, -P(O)(OR)-, -P(O)(R)-, -P(O)(NR2)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by, here: Each -Cy- independently comprises phenylenyl, 8- to 10-membered bicyclic aryrenyl, 3- to 8-membered saturated or partially unsaturated carbocyclilenyl, 6- to 11-membered saturated or partially unsaturated spirocarbocyclilenyl, 5- to 12-membered, bridged or unbridged, bicyclic saturated or partially unsaturated carbocyclilenyl, 4- to 10-membered saturated or partially unsaturated heterocyclilenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, and 6- to 11-membered saturated cyclilenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur. Alternatively, a substituted divalent ring, optionally selected from a partially unsaturated spiroheterocrylenyl, a 5- to 12-membered bridged or unbridged bicyclic saturated or partially unsaturated heterocyclenyl, a 5- to 6-membered heteroarylenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, or an 8- to 10-membered bicyclic heteroarylenyl having 1 to 5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur; TBM is the target binding site; m is 0, 1, or 2; n is 0, 1, 2, 3, or 4; p is either 0 or 1, and if p is 0, the bond connecting ring A and ring B is: [ka] It is connected; Each of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and Each R is independently a hydrogen atom or a optionally substituted group, and this optionally substituted group is C 1~6 A 4- to 7-membered saturated or partially unsaturated heterocyclic compound having one or two heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur. Furthermore, it is selected from a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same nitrogen atom, together with the atom between them, form a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to this nitrogen atom.

[0075] As described above, in a particular embodiment, the present invention relates to formula II-B: [ka] The compound or a pharmaceutically acceptable salt thereof is provided, in formula II-B: X 1 These are covalent bonds, -CH2-, -C(O)-, -C(S)-, or [ka] It is the bivalent part selected from; R 1 C is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, or substituted as needed. 1~4 It is aliphatic; Ring A is, [ka] [ka] A monoring or biring ring selected from; Each R 2 These are independently hydrogen, -R 4 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Ring B is selected from a 6-membered aryl group containing 0 to 2 nitrogen atoms, or a 5-membered heteroaryl group containing 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Each R 3 These are independently hydrogen, -R 4 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Each R 4 C 1~6 A optionally substituted group selected from a 4- to 7-membered saturated or partially unsaturated heterocyclic ring having one or two heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered heteroaryl ring having one or four heteroatoms independently selected from nitrogen, oxygen, and sulfur; R 5 is hydrogen, C 1~4 It is aliphatic or -CN; L is a covalent or divalent, saturated or unsaturated, linear or branched C 1~50 It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of each other: -Cy-, -O-, -N(R)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by, here: Each -Cy- independently becomes phenylenyl, an 8- to 10-membered bicyclic aryrenyl, a 4- to 7-membered saturated or partially unsaturated carbocyclilenyl, or a 4- to 7-membered saturated or partially unsaturated A divalent ring, optionally substituted, selected from spirocarbocyclilenyl, 8- to 10-membered bicyclic saturated or partially unsaturated carbocyclilenyl, 4- to 7-membered saturated or partially unsaturated heterocyclilenyl having 1 or 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 4- to 7-membered saturated or partially unsaturated spiroheteroryl, 8- to 10-membered bicyclic saturated or partially unsaturated heterocyclilenyl having 1 or 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 5- to 6-membered heteroarylenyl having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 8- to 10-membered bicyclic heteroarylenyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; TBM is the target binding site; m is 0, 1, or 2; n is 0, 1, 2, 3, or 4; p is either 0 or 1; Each of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and Each R is independently a hydrogen atom or a optionally substituted group, and this optionally substituted group is C 1~6 Selected from 4- to 7-membered saturated or partially unsaturated heterocyclic rings having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and 5- to 6-membered heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same nitrogen atom, together with the atom between them, form a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to this nitrogen atom.

[0076] As described above, in a particular embodiment, the present invention relates to formula II'-B: [ka] The compound or a pharmaceutically acceptable salt thereof is provided, in formula II'-B: X 1 These are covalent bonds, -CH2-, -C(O)-, -C(S)-, or [ka] It is the bivalent part selected from; R 1 C is hydrogen, deuterium, halogen, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, or substituted as needed. 1~4 It is aliphatic; Ring A is, [ka] [ka] A monoring or biring ring selected from; Each R 2 These are independently hydrogen, -R 4 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Ring B is selected from a 6-membered aryl group containing 0 to 2 nitrogen atoms, or a 5-membered heteroaryl group containing 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Each R 3 These are independently hydrogen, -R 4 , halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, or -N(R)S(O)2R; Each R 4 C 1~6 A optionally substituted group selected from a 4- to 7-membered saturated or partially unsaturated heterocyclic ring having one or two heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered heteroaryl ring having one or four heteroatoms independently selected from nitrogen, oxygen, and sulfur; R 5 is hydrogen, C 1~4 It is aliphatic or -CN; L is a covalent or divalent, saturated or unsaturated, linear or branched C 1~50 It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of each other: -Cy-, -O-, -N(R)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by, here: Each -Cy- is independently a phenylenyl, an 8- to 10-membered bicyclic aryrenyl, a 4- to 7-membered saturated or partially unsaturated carbocyclilenyl, a 4- to 7-membered saturated or partially unsaturated spirocarbocyclilenyl, an 8- to 10-membered bicyclic saturated or partially unsaturated carbocyclilenyl, a 4- to 7-membered saturated or partially unsaturated heterocyclilenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 4- to 7-membered saturated cyclilenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur. A optionally substituted divalent ring selected from a summed or partially unsaturated spiroheterolenyl, an 8- to 10-membered bicyclic saturated or partially unsaturated heterocyclenyl having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered heteroaryrenyl having one or four heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryrenyl having one or five heteroatoms independently selected from nitrogen, oxygen, or sulfur; TBM is the target binding site; m is 0, 1, or 2; n is 0, 1, 2, 3, or 4; p is either 0 or 1; Each of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and Each R is independently a hydrogen atom or a optionally substituted group, and this optionally substituted group is C 1~6 Selected from 4- to 7-membered saturated or partially unsaturated heterocyclic rings having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and 5- to 6-membered heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same nitrogen atom, together with the atom between them, form a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to this nitrogen atom.

[0077] In a particular embodiment, the present invention relates to formula II''-B: [ka] The compound or a pharmaceutically acceptable salt thereof is provided, in formula II''-B: X 1 These are covalent bonds, -C(R)2-, -C(O)-, -C(S)-, -P(O)(OR)-, -P(O)(R)-, -P(O)(NR2)-, -S(O)-, -S(O)2-, or [ka] It is the bivalent part selected from; X 2 is a carbon or silicon atom; X 3 is a divalent part selected from -C(R)2-, -N(R)-, -CF2-, -CHF-, -S-, or -O-; X 4 is a divalent part selected from a covalent bond or -C(R)2-; [ka] It is either a single bond or a double bond; R 1 This includes hydrogen, deuterium, halogens, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, -P(O)(OR)2, -P(O)(NR2)OR, -P(O)(NR2)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, and substituted C as needed. 1~4 It is aliphatic, or: R 1 and X 1 or X 4 These atoms, together with the atoms in between, form a 5- to 7-membered saturated, partially unsaturated carbocyclic ring, or a heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Ring A is, [ka] A monoring or biring ring selected from; Each R 2 These are independently hydrogen, deutherium, and -R 6 , halogen, -CN, -NO2, -OR, -SR, -NR2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, - OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)S(O)2NR2, -P(O)(OR)2, -P(O)(NR2)OR, or -P(O)(NR2)2; Ring B is selected from a 6-membered aryl containing 0 to 3 nitrogen atoms, or a 5-membered heteroaryl having 1 to 3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur; Each R 3 is hydrogen, deutherium, -R 4 , halogen, -CN, -NO2, -OR, -NR2, -SR, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, - C(O)NR(OR), -OC(O)R, -OC(O)NR2, -OP(O)(OR)2, -OP(O)(NR2)2, -OP(O)(OR)NR2, -N(R)C(O)R, Selected from -N(R)C(O)OR, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)S(O)2NR2, -N(R)P(O)(OR)2, -N(R)P(O)(OR)NR2, -P(O)(OR)2, -P(O)(NR2)OR, -P(O)(NR2)2, -Si(OH)2R, -Si(OH)(R)2, or -Si(R)3; Each R 4 C 1~6A optionally substituted group selected from aliphatic, phenyl, boron, nitrogen, oxygen, silicon, or sulfur-independently saturated or partially unsaturated heterocyclic rings of 4 to 7 members having 1 to 3 heteroatoms, and 5 to 6 members having 1 to 4 heteroatoms, independently selected from nitrogen, oxygen, and sulfur; R 5 This consists of hydrogen, deutherium, and optionally substituted C. 1~4 It is aliphatic or -CN; L is a covalent or divalent, saturated or unsaturated, linear or branched C 1~50 It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of -Cy-, -O-, -N(R)-, -Si(R)2-, -Si(OH)(R)-, -Si(OH)2-, -P(O)(OR)-, -P(O)(R)-, -P(O)(NR2)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by, here: Each -Cy- independently comprises phenylenyl, 8- to 10-membered bicyclic aryrenyl, 3- to 8-membered saturated or partially unsaturated carbocyclilenyl, 6- to 11-membered saturated or partially unsaturated spirocarbocyclilenyl, 5- to 12-membered, bridged or unbridged, bicyclic saturated or partially unsaturated carbocyclilenyl, 4- to 10-membered saturated or partially unsaturated heterocyclilenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, and 6- to 11-membered saturated cyclilenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur. Alternatively, a substituted divalent ring, optionally selected from a partially unsaturated spiroheterocrylenyl, a 5- to 12-membered bridged or unbridged bicyclic saturated or partially unsaturated heterocyclenyl, a 5- to 6-membered heteroarylenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, or an 8- to 10-membered bicyclic heteroarylenyl having 1 to 5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur; TBM is the target binding site; m is 0, 1, or 2; n is 0, 1, 2, 3, or 4; p is either 0 or 1; Each of q is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and Each R is independently a hydrogen, deuterium, or optionally substituted group, and this optionally substituted group is C 1~6 Selected from 4- to 7-membered saturated or partially unsaturated heterocyclic rings having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and 5- to 6-membered heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same nitrogen atom, together with the atom between them, form a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to this nitrogen atom.

[0078] As defined above and as described herein, X 1 is a covalent bond, -CH2-, -C(R)2-, -C(O)-, -C(S)-, -CH(R)-, -CH(CF3)-, -P(O)(OR)-, -P(O)(R)-, -P(O)(NR2)-, -S(O)-, -S(O)2-, or [ka] This is the bivalent part selected from the given set.

[0079] In some embodiments, X 1 It is a covalent bond. In some embodiments, X 1 is -CH2-. In some embodiments, X 1 is -C(R)2-. In some embodiments, X 1 is -C(O)-. In some embodiments, X 1 is -C(S)-. In some embodiments, X 1 is -CH(R)-. In some embodiments, X 1 is -CH(CF3)-. In some embodiments, X 1 is -P(O)(OR)-. In some embodiments, X 1 is -P(O)(R)-. In some embodiments, X 1 is -P(O)(NR2)-. In some embodiments, X 1 is -S(O)-. In some embodiments, X 1 is -S(O)2-. In some embodiments, X 1 teeth [ka] That is the case.

[0080] In some embodiments, X 1 The option is selected from those shown in Table 1 below.

[0081] As defined above and as described herein, X 2 These are carbon atoms or silicon atoms.

[0082] In some embodiments, X 2 X is a carbon atom. In some embodiments, X 2 It is a silicon atom.

[0083] In some embodiments, X 2 The option is selected from those shown in Table 1 below.

[0084] As defined above and as described herein, X 3 This is a divalent part selected from -CH2-, -C(R)2-, -N(R)-, -CF2-, -CHF-, -S-, -CH(R)-, or -O-.

[0085] In some embodiments, X 3 is -CH2-. In some embodiments, X 1 is -C(R)2-. In some embodiments, X 3 is -N(R)-. In some embodiments, X 3 is -CF2-. In some embodiments, X 3 is -CHF-. In some embodiments, X 3 is -S-. In some embodiments, X 3 is -CH(R)-. In some embodiments, X 3 It is -O-.

[0086] In some embodiments, X 3 The option is selected from those shown in Table 1 below.

[0087] As defined above and as described herein, X 4 This is a divalent part selected from a covalent bond, -CH2-, or -C(R)2-.

[0088] In some embodiments, X 4 It is a covalent bond. In some embodiments, X 4 is -CH2-. In some embodiments, X 4 is -C(R)2-.

[0089] In some embodiments, X 4 The option is selected from those shown in Table 1 below.

[0090] As defined above and described herein, R 1 This includes hydrogen, deuterium, halogens, -CN, -OR, -SR, -S(O)R, -S(O)2R, -NR2, -P(O)(OR)2, -P(O)(NR2)OR, -P(O)(NR2)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, and substituted C as needed. 1~4 Is it aliphatic, or R 1 and X 1 or X 4 These atoms, together with the atoms in between, form a 5- to 7-membered saturated or partially unsaturated carbocyclic ring, or a heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0091] In some embodiments, R 1 is hydrogen. In some embodiments, R 1 is deutherium. In some embodiments, R 1 is a halogen. In some embodiments, R 1 is -CN. In some embodiments, R 1 is -OR. In some embodiments, R 1 is -SR. In some embodiments, R 1is -S(O)R. In some embodiments, R 1 is -S(O)2R. In some embodiments, R 1 is -NR2. In some embodiments, R 1 is -P(O)(OR)2. In some embodiments, R 1 is -P(O)(NR2)OR. In some embodiments, R 1 is -P(O)(NR2)2. In some embodiments, R 1 is -Si(OH)2R. In some embodiments, R 1 is -Si(OH)(R)2. In some embodiments, R 1 is -Si(R)3. In some embodiments, R 1 C is replaced as needed. 1~4 It is aliphatic. In some embodiments, R 1 and X 1 or X 4 These atoms, together with the atoms in between, form a 5- to 7-membered saturated or partially unsaturated carbocyclic ring, or a heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0092] In some embodiments, R 1 The option is selected from those shown in Table 1 below.

[0093] As defined above and described herein, each R 2 These are independently hydrogen, deutherium, and -R 6, halogen, -CN, -NO2, -OR, -SR, -N(R)2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)S(O)2NR2, -P(O)(OR)2, -P(O)(NR2)OR, or -P(O)(NR2)2.

[0094] In some embodiments, R 2 is hydrogen. In some embodiments, R 2 is deutherium. In some embodiments, R 2 ha-R 6 In some embodiments, R 2 is a halogen. In some embodiments, R 2 is -CN. In some embodiments, R 2 is -NO2. In some embodiments, R 2 is -OR. In some embodiments, R 2 is -Si(OH)2R. In some embodiments, R 2 is -Si(OH)(R)2. In some embodiments, R 2 is -SR. In some embodiments, R 2 is -NR2. In some embodiments, R 2 is -Si(R)3. In some embodiments, R 2 is -S(O)2R. In some embodiments, R 2 is -S (O)2NR2 is the case in some embodiments. 2 is -S(O)R. In some embodiments, R 2 is -C(O)R. In some embodiments, R 2 is -C(O)OR. In some embodiments, R 2is -C(O)NR2. In some embodiments, R 2 is -C(O)N(R)OR. In some embodiments, R 2 is -OC(O)R. In some embodiments, R 2 is -OC(O)NR2. In some embodiments, R 2 is -N(R)C(O)OR. In some embodiments, R 2 is -N(R)C(O)R. In some embodiments, R 2 is -N(R)C(O)NR2. In some embodiments, R 2 is -N(R)S(O)2R. In some embodiments, R 2 is -P(O)(OR)2. In some embodiments, R 2 is -P(O)(NR2)OR. In some embodiments, R 2 is -P(O)(NR2)2.

[0095] In some embodiments, R 2 The option is selected from those shown in Table 1 below.

[0096] As defined above and described herein, ring A is, [ka] [ka] It is a biring or triring ring selected from the following.

[0097] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

[0098] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

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

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

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

[0102] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] That is the case.

[0103] In some embodiments, each ring B is [ka] In some embodiments, each ring B is [ka] In some embodiments, each ring B is [ka] In some embodiments, each ring B is [ka] In some embodiments, each ring B is [ka] That is the case.

[0104] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] That is the case.

[0105] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] .

[0106] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] That is the case.

[0107] In some embodiments, ring B is [ka] [ka] Selected from.

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

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

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

[0111] In some embodiments, [ka] The option is selected from those shown in Table 1 below.

[0112] As defined above and described herein, R 3 These are hydrogen, deuterium, halogen, -CN, -NO2, -OR, -NR2, -SR, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NR(OR), -OC(O)R, -OC(O)NR2, -OP(O)(OR)2, -OP(O)(NR2)2, -OP(O)(OR)NR2, -N(R )C(O)R, -N(R)C(O)OR, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)S(O)2NR2, -N(R)P(O)(OR)2, -N(R)P(O )(OR)NR2, -P(O)(OR)2, -P(O)(NR2)OR, -P(O)(NR2)2, -Si(OH)2R, -Si(OH)(R)2, or -Si(R)3.

[0113] In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is deutherium. In some embodiments, R 3 is a halogen. In some embodiments, R 3 is -CN. In some embodiments, R 3 is -NO2. In some embodiments, R 3 is -OR. In some embodiments, R 3 is -NR2. In some embodiments, R 3 is -SR. In some embodiments, R 3 is -S(O)2R. In some embodiments, R 3 is -S(O)2NR2. In some embodiments, R 3 is -S(O)R. In some embodiments, R 3 is -C(O)R. Several embodiments In R 3 is -C(O)OR. In some embodiments, R 3 is -C(O)NR2. In some embodiments, R 3is -C(O)NR(OR). In some embodiments, R 3 is -OC(O)R. In some embodiments, R 3 is -OC(O)NR2. In some embodiments, R 3 is -OP(O)(OR)2. In some embodiments, R 3 is -OP(O)(NR2)2. In some embodiments, R 3 is -OP(O)(OR)NR2. In some embodiments, R 3 is -N(R)C(O)R. In some embodiments, R 3 is -N(R)C(O)OR. In some embodiments, R 3 is -N(R)C(O)NR2. In some embodiments, R 3 is -N(R)S(O)2R. In some embodiments, R 3 is -N(R)S(O)2NR2. In some embodiments, R 3 is -N(R)P(O)(OR)2. In some embodiments, R 3 is -N(R)P(O)(OR)NR2. In some embodiments, R 3 is -P(O)(OR)2. In some embodiments, R 3 is -P(O)(NR2)OR. In some embodiments, R 3 is -P(O)(NR2)2. In some embodiments, R 3 is -Si(OH)2R. In some embodiments, R 3 is -Si(OH)(R)2. In some embodiments, R 3 It is -Si(R)3.

[0114] In some embodiments, R 3 is methyl. In some embodiments, R 3 is -OCH3. In some embodiments, R 3 It is chloroform.

[0115] In some embodiments, R 3 The option is selected from those shown in Table 1 below.

[0116] As defined above and described herein, each R 4 These are independently hydrogen, deutherium, and -R 6 These are halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)2R, -P(O)(OR)2, -P(O)(NR2)OR, or -P(O)(NR2)2.

[0117] In some embodiments, R 4 is hydrogen. In some embodiments, R 4 ha-R 6 In some embodiments, R 4 is a halogen. In some embodiments, R 4 is -CN. In some embodiments, R 4 is -NO2. In some embodiments, R 4 is -OR. In some embodiments, R 4 is -SR. In some embodiments, R 4 is -NR2. In some embodiments, R 4 is -S(O)2R. In some embodiments, R 4 is -S(O)2NR2. In some embodiments, R 4 is -S(O)R. In some embodiments, R 4 is -C(O)R. In some embodiments, R 4 is -C(O)OR. In some embodiments, R 4 is -C(O)NR2. In some embodiments, R 4 is -C(O)N(R)OR. In some embodiments, R4 is -OC(O)R. In some embodiments, R 4 is -OC(O)NR2. In some embodiments, R 4 is -N(R)C(O)OR. In some embodiments, R 4 is -N(R)C(O)R. In some embodiments, R 4 is -N(R)C(O)NR2. In some embodiments, R 4 is -N(R)S(O)2R. In some embodiments, R 4 is -P(O)(OR)2. In some embodiments, R 4 is -P(O)(NR2)OR. In some embodiments, R 4 is -P(O)(NR2)2.

[0118] In some embodiments, R 4 is methyl. In some embodiments, R 4 is ethyl. In some embodiments, R 4 It is cyclopropyl.

[0119] In some embodiments, R 4 The option is selected from those shown in Table 1 below.

[0120] As defined above and described herein, R 5 This consists of hydrogen, deutherium, and optionally substituted C. 1~4 It is aliphatic or -CN.

[0121] In some embodiments, R 5 is hydrogen. In some embodiments, R 5 is deutherium. In some embodiments, R 5 C is replaced as needed. 1~4 It is aliphatic. In some embodiments, R 5 is -CN.

[0122] In some embodiments, R 5 The option is selected from those shown in Table 1 below.

[0123] As defined above and described herein, each R 6 C 1~6 The group is optionally substituted, and is selected from aliphatic, phenyl, boron, nitrogen, oxygen, silicon, or sulfur-independently-selected 4- to 7-membered saturated or partially unsaturated heterocyclic rings, as well as 5- to 6-membered heteroaryl rings, which have 1 to 4 heteroatoms-independently-selected boron, nitrogen, oxygen, silicon, and sulfur.

[0124] In some embodiments, R 6 C is replaced as needed. 1~6 It is aliphatic. In some embodiments, R 6 R is a phenyl compound that is substituted as needed. In some embodiments, R 6 R is a optionally substituted 4- to 7-membered saturated or partially unsaturated heterocyclic ring having 1 to 3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, R 6 This is an optionally substituted 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur.

[0125] In some embodiments, R 6 The option is selected from those shown in Table 1 below.

[0126] As defined above and as described herein, L is a covalent, or divalent, saturated or unsaturated, linear or branched C 1~50It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of -Cy-, -O-, -N(R)-, -Si(R)2-, -Si(OH)(R)-, -Si(OH)2-, -P(O)(OR)-, -P(O)(R)-, -P(O)(NR2)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by.

[0127] In some embodiments, L is a covalent bond. In some embodiments, L is a divalent, saturated or unsaturated, linear or branched C 1~50 It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of -Cy-, -O-, -N(R)-, -Si(R)2-, -Si(OH)(R)-, -Si(OH)2-, -P(O)(OR)-, -P(O)(R)-, -P(O)(NR2)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by.

[0128] In some embodiments, L is [ka] In some embodiments, L is [ka] In some embodiments, L is [ka] In some embodiments, L is [ka] In some embodiments, L is [ka] That is the case.

[0129] In some embodiments, L is [ka] In some embodiments, L is [ka] In some embodiments, L is [ka] In some embodiments, L is [ka] In some embodiments, L is [ka] In some embodiments, L is [ka] In some embodiments, L is [ka] In some embodiments, L is [ka] That is the case.

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

[0131] As defined above and described herein, each -Cy- is independently phenylenyl, 8- to 10-membered bicyclic aryrenyl, 3- to 8-membered saturated or partially unsaturated carbocyclilenyl, 6- to 11-membered saturated or partially unsaturated spirocarbocyclilenyl, 5- to 12-membered, bridged or unbridged, bicyclic saturated or partially unsaturated carbocyclilenyl, 4- to 10-membered saturated or partially unsaturated heterocyclyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur. A 6- to 11-membered saturated or partially unsaturated spiroheterolenyl having 1 to 4 heteroatoms independently selected from lenyl, boron, nitrogen, oxygen, silicon, phosphorus, or sulfur; a 5- to 12-membered bridged or unbridged bicyclic saturated or partially unsaturated heterocyclelenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur; a 5- to 6-membered heteroarylenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur. It is a divalent ring, optionally substituted, selected from an 8- to 10-membered bicyclic heteroarylenyl having 1 to 5 heteroatoms independently selected from ru, or boron, nitrogen, oxygen, silicon, phosphorus, or sulfur.

[0132] In some embodiments, -Cy- is a optionally substituted divalent ring selected from phenylenyl. In some embodiments, -Cy- is an optionally substituted 8- to 10-membered bicyclic aryrenyl. In some embodiments, -Cy- is an optionally substituted 3- to 8-membered saturated or partially unsaturated carbocyclilenyl. In some embodiments, -Cy- is an optionally substituted 6- to 11-membered saturated or partially unsaturated spirocarbocyclilenyl. In some embodiments, -Cy- is an optionally substituted 5- to 12-membered, bridged or unbridged, bicyclic saturated or partially unsaturated carbocyclilenyl. In some embodiments, -Cy- is an optionally substituted 4- to 10-membered saturated or partially unsaturated heterocyclilenyl having 1- to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur. In some embodiments, -Cy- is an optionally substituted 6- to 11-membered saturated or partially unsaturated spiroheterocyclelenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur. In some embodiments, -Cy- is an optionally substituted 5- to 12-membered bridged or unbridged bicyclic saturated or partially unsaturated heterocyclelenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur. In some embodiments, -Cy- is an optionally substituted 5- to 6-membered heteroarylenyl having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur, or an 8- to 10-membered bicyclic heteroarylenyl having 1 to 5 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, phosphorus, or sulfur.

[0133] In some embodiments, -Cy- is [ka] That is the case.

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

[0135] As defined above and described herein, the TBM is the target binding site.

[0136] In some embodiments, the TBM is the target binding site.

[0137] In some embodiments, the 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, where this drug is: [ka] It is bonded to with any modifiable carbon, oxygen, sulfur, or nitrogen atom.

[0139] In some embodiments, TBM is selected from one of the drugs listed in Table 2, where this drug is: [ka] It is bonded to with any modifiable carbon, oxygen, sulfur, or nitrogen atom.

[0140] In some embodiments, TBM is selected from one of the drugs listed in Table 2, where this drug is: [ka] It is bonded to with any modifiable carbon, oxygen, sulfur, or nitrogen atom.

[0141] In some embodiments, TBM is selected from one of the drugs listed in Table 2, where this drug is: [ka] It is bonded to with any modifiable carbon, oxygen, sulfur, or nitrogen atom.

[0142] In some embodiments, TBM [ka] In some embodiments, the TBM is [ka] In some embodiments, the TBM is [ka] In some embodiments, the TBM is [ka] In some embodiments, the TBM is [ka] In some embodiments, the TBM is [ka] In some embodiments, the TBM is [ka] In some embodiments, the TBM is [ka] That is the case.

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

[0144] As defined above and as 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 shown in Table 1 below.

[0147] As defined above and as 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 shown in Table 1 below.

[0150] As defined above and as described herein, each R is independently hydrogen, deutherium, or a optionally substituted group, the optionally substituted group being C 1~6 Selected from aliphatic, phenyl, boron, nitrogen, oxygen, silicon, and sulfur, 4- to 7-membered saturated or partially unsaturated heterocyclic rings having 1 to 3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur, and 5- to 6-membered heteroaryl rings having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur, or two R groups on the same nitrogen, together with the atom between them, in addition to this nitrogen, boron, It forms a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, silicon, and sulfur.

[0151] In some embodiments, R is hydrogen. In some embodiments, R is deuterium. In some embodiments, R is a substituted C as needed. 1~6 It is aliphatic. In some embodiments, R is optionally substituted phenyl. In some embodiments, R is optionally substituted 4- to 7-membered saturated or partially unsaturated heterocyclic ring having 1 to 3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur. In some embodiments, R is optionally substituted 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur. In some embodiments, two R groups on the same nitrogen, together with the atom between them, form a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur, in addition to this nitrogen.

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

[0153] In some embodiments, the present invention is X 1 , R 1 , R 5 , R, -Cy-, and TBM are as described above for formula I and in this specification, and ring A, ring B, R 2 , R 3 , R 4 L, m, n, p, and q are given for the following formulas II-A and II-B, and provide compounds of formula II-A or II-B as described herein.

[0154] As defined above and described herein, ring A is, [ka] [ka] It is a single-ring or double-ring selected from the following.

[0155] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

[0156] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

[0157] In some embodiments, A is [ka] It is a monoring or biring ring selected from the following.

[0158] In some embodiments, A is [ka] [ka] [ka] [ka] It is a monoring or biring ring selected from the following.

[0159] In some embodiments, A is [ka] Selected from.

[0160] In some embodiments, A is [ka] Selected from.

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

[0162] As defined above and described herein, each R 2 These are independently hydrogen, deutherium, and -R 4 , halogen, -CN, -NO2, -OR, -SR, -NR2, -Si(OH)2R, -Si(OH)(R)2, -Si(R)3, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, - OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)S(O)2NR2, -P(O)(OR)2, -P(O)(NR2)OR, or -P(O)(NR2)2.

[0163] In some embodiments, R 2 is hydrogen. In some embodiments, R 2 is deutherium. In some embodiments, R 2 ha-R 4 In some embodiments, R 2is a halogen. In some embodiments, R 2 is -CN. In some embodiments, R 2 is -NO2. In some embodiments, R 2 is -OR. In some embodiments, R 2 is -Si(OH)2R. In some embodiments, R 2 It is -Si(OH)(R)2. Some In the embodiment, R 2 is -SR. In some embodiments, R 2 is -NR2. In some embodiments, R 2 is -Si(R)3. In some embodiments, R 2 is -S(O)2R. In some embodiments, R 2 is -S(O)2NR2. In some embodiments, R 2 is -S(O)R. In some embodiments, R 2 is -C(O)R. In some embodiments, R 2 is -C(O)OR. In some embodiments, R 2 is -C(O)NR2. In some embodiments, R 2 is -C(O)N(R)OR. In some embodiments, R 2 is -OC(O)R. In some embodiments, R 2 is -OC(O)NR2. In some embodiments, R 2 is -N(R)C(O)OR. In some embodiments, R 2 is -N(R)C(O)R. In some embodiments, R 2 is -N(R)C(O)NR2. In some embodiments, R 2 is -N(R)S(O)2R. In some embodiments, R 2 is -P(O)(OR)2. In some embodiments, R 2 is -P(O)(NR2)OR. In some embodiments, R 2is -P(O)(NR2)2.

[0164] In some embodiments, R 2 It is methyl.

[0165] In some embodiments, R 2 The option is selected from those shown in Table 1 below.

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

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

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

[0169] As defined above and described herein, each R 3 These are independently hydrogen, deuterium, halogen, -CN, -NO2, -OR, -NR2, -SR, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)NR(OR), -OC(O)R, -OC(O)NR2, -OP(O)(OR)2, -OP(O)(NR2)2, -OP(O)(OR)NR2, -N (R)C(O)R, -N(R)C(O)OR, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)S(O)2NR2, -N(R)P(O)(OR)2, -N(R)P( O)(OR)NR2, -P(O)(OR)2, -P(O)(NR2)OR, -P(O)(NR2)2, -Si(OH)2R, -Si(OH)(R)2, or -Si(R)3.

[0170] In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is deutherium. In some embodiments, R 3 is a halogen. In some embodiments, R 3 is -CN. In some embodiments, R 3 is -NO2. In some embodiments, R 3 is -OR. In some embodiments, R 3 is -NR2. In some embodiments, R 3 is -SR. In some embodiments, R 3 is -S(O)2R. In some embodiments, R 3 is -S(O)2NR2. In some embodiments, R 3 is -S(O)R. In some embodiments, R 3 is -C(O)R. In some embodiments, R 3 is -C(O)OR. In some embodiments, R 3 is -C(O)NR2. In some embodiments, R 3 is -C(O)NR(OR). In some embodiments, R 3 is -OC(O)R. In some embodiments R 3 is -OC(O)NR2. In some embodiments, R 3 is -OP(O)(OR)2. In some embodiments, R 3 is -OP(O)(NR2)2. In some embodiments, R 3 is -OP(O)(OR)NR2. In some embodiments, R 3 is -N(R)C(O)R. In some embodiments, R 3 is -N(R)C(O)OR. In some embodiments, R 3 is -N(R)C(O)NR2. In some embodiments, R 3is -N(R)S(O)2R. In some embodiments, R 3 is -N(R)S(O)2NR2. In some embodiments, R 3 is -N(R)P(O)(OR)2. In some embodiments, R 3 is -N(R)P(O)(OR)NR2. In some embodiments, R 3 is -P(O)(OR)2. In some embodiments, R 3 is -P(O)(NR2)OR. In some embodiments, R 3 is -P(O)(NR2)2. In some embodiments, R 3 is -Si(OH)2R. In some embodiments, R 3 is -Si(OH)(R)2. In some embodiments, R 3 It is -Si(R)3.

[0171] In some embodiments, R 3 The option is selected from those shown in Table 1 below.

[0172] As defined above and described herein, each R 4 C 1~6 The group is optionally substituted, and is selected from aliphatic, phenyl, boron, nitrogen, oxygen, silicon, or sulfur-independently-selected 4- to 7-membered saturated or partially unsaturated heterocyclic rings, as well as 5- to 6-membered heteroaryl rings, which have 1 to 4 heteroatoms-independently-selected boron, nitrogen, oxygen, silicon, and sulfur.

[0173] In some embodiments, R 4 C is replaced as needed. 1~6 It is aliphatic. In some embodiments, R 4 R is a phenyl compound that is substituted as needed. In some embodiments, R 4R is a optionally substituted 4- to 7-membered saturated or partially unsaturated heterocyclic ring having 1 to 3 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, or sulfur. In some embodiments, R 4 This is an optionally substituted 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from boron, nitrogen, oxygen, silicon, and sulfur.

[0174] In some embodiments, R 4 It is methyl.

[0175] In some embodiments, R 4 The option is selected from those shown in Table 1 below.

[0176] As defined above and as described herein, L is a covalent, or divalent, saturated or unsaturated, linear or branched C 1~50 It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of -Cy-, -O-, -N(R)-, -Si(R)2-, -Si(OH)(R)-, -Si(OH)2-, -P(O)(OR)-, -P(O)(R)-, -P(O)(NR2)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by.

[0177] In some embodiments, L is a covalent bond. In some embodiments, L is a divalent, saturated or unsaturated, linear or branched C 1~50It is a hydrocarbon chain, where L has 0 to 6 methylene units that are independent of -Cy-, -O-, -N(R)-, -Si(R)2-, -Si(OH)(R)-, -Si(OH)2-, -P(O)(OR)-, -P(O)(R)-, -P(O)(NR2)-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O)2-, -N(R)S(O)2-, -S(O)2N(R)-, -N(R)C(O)-, -C(O)N(R)-, -OC(O)N(R)-, -N(R)C(O)O-, [ka] It has been replaced by.

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

[0179] As defined above and as 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 shown in Table 1 below.

[0182] As defined above and as 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 shown in Table 1 below.

[0185] As defined above and described herein, p is either 0 or 1, where if p is 0, the bond connecting ring A and ring B is [ka] It is connected.

[0186] In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 0, and the bond connecting ring A and ring B is [ka] It is connected.

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

[0188] As defined above and as 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 shown in Table 1 below.

[0191] In a preferred aspect of the present invention, the TBM group is a group that binds to a target protein. The target of the TBM group is selected from a number of proteins that are expressed in a cell and whose sequence is found in at least a portion of that cell, and which can bind to the TBM group. The term “protein” includes oligopeptides and polypeptide sequences of sufficient length that can bind to the TBM group according to the present invention. As described herein, any protein in a eukaryotic system is a target for ubiquitination mediated by the compounds according to the present invention.

[0192] Examples of TBM groups according to the present invention include any moiety that specifically binds to a protein (bounds to a target protein), and non-limiting examples of small target protein moieties include, among many others, Hsp90 inhibitors, kinase inhibitors, HDM2 and MDM2 inhibitors, compounds that target human BET bromodomain-containing proteins, HDAC inhibitors, human lysine methyltransferase inhibitors, angiogenesis inhibitors, nuclear hormone receptor compounds, immunosuppressive compounds, and compounds that target aryl hydrocarbon receptors (AHRs). The compositions described below exemplify some of the members of these nine types of small target protein binding moieties. Such small target protein binding moieties also include pharmaceutically acceptable salts, enantiomers, solvates and polymorphisms of these compositions, as well as other small molecules that can target the protein of interest. These binding moieties bind to a ubiquitin ligase binding moiety, possibly via a linker, for the purpose of presenting the target protein (to which the protein target moiety is bound) near this ubiquitin ligase for ubiquitination and degradation.

[0193] Any protein that can bind to a target-binding site or a TBM group and is acted upon or degraded by a ubiquitin ligase is a target protein according to the present invention. Generally, target proteins include, for example, structural proteins, receptors, enzymes, cell surface proteins, proteins involved in the integrated function of cells (such as proteins involved in catalytic activity, aromatase activity, motility activity, helicase activity, metabolic processes (anabolism and catabolism), antioxidant activity, proteolysis, and biosynthesis), kinase activity, oxidoreductase activity, transferase activity, hydrolase activity, lyase activity, isomerase activity, ligase activity, enzyme regulator activity, signal transducer activity, structural molecular activity, binding activity (proteins, lipids and carbohydrates), receptor activity, cell motility, membrane fusion, cell communication, regulation of biological processes, development, cell differentiation, proteins that respond to stimuli, behavioral proteins, cell adhesion proteins, proteins involved in cell death, and proteins involved in transport (such as protein transporter activity, nuclear transport, ion transporter activity, channel transporter activity, carrier activity, permease activity, secretory activity, electron transporter activity, pathogenesis, chaperone regulator activity, nucleic acid binding activity, transcription regulator activity, extracellular organization and biodevelopmental activity, and translation regulator activity). Target proteins may include those derived from eukaryotic and prokaryotic cells, but among many others, particularly humans (as targets for drug therapy), other animals (including domesticated animals), microorganisms (for determining targets for antibiotics and other antimicrobial agents and plants), and even viruses.

[0194] A TBM (or target binding site) is a small molecule that can or does bind to the target protein of interest.

[0195] Some embodiments of the present invention relate to TBMs, including but 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 aryl hydrocarbon receptors (AHRs).

[0196] In some embodiments, the TBM is [ka] [ka] A BRD ligand selected from, where R is [ka] [ka] This represents a connection to something.

[0197] In some embodiments, the TBM is [ka] [ka] A CREBBP ligand selected from, where R is [ka] [ka] This represents a connection to; X is N or C; and n is between 0 and 8.

[0198] In some embodiments, the TBM is [ka] A SMARCA4 / PB1 / SMARCA2 ligand selected from, where R is, [ka] [ka] This represents a connection to; X is N or C; and n is between 0 and 8.

[0199] In some embodiments, the TBM is [ka] A TRIM24 / BRPF1 ligand selected from, where R is [ka] [ka] This represents a connection to; and n is between 0 and 8.

[0200] In some embodiments, the TBM is [ka] [ka] A glucocorticoid receptor ligand selected from, where R is [ka] [ka] This represents a connection to something.

[0201] In some embodiments, the TBM is [ka] [ka] An estrogen / androgen receptor ligand selected from, where R is, [ka] [ka] This represents a connection to something.

[0202] In some embodiments, the TBM is [ka] A DOT1L ligand selected from, where R is [ka] This represents a connection to; X is N or C; and n is between 0 and 8.

[0203] In some embodiments, the TBM is [ka] A BRAF ligand selected from, where R is [ka] [ka] This represents a connection to something.

[0204] In some embodiments, the TBM is [ka] [ka] A Ras ligand selected from, where R is [ka] This represents a connection to something.

[0205] In some embodiments, the TBM is [ka] A RasG12C ligand selected from, where R is, [ka] [ka] This represents a connection to something.

[0206] In some embodiments, the TBM is [ka] A Her3 ligand selected from, where R is [ka] This represents a bond to ; and R' is -CH2CH3 or -CH=CH2.

[0207] In some embodiments, the TBM is [ka] A Bcl-2 / Bcl-XL ligand selected from, where R is, [ka] [ka] This represents a connection to something.

[0208] In some embodiments, the TBM is [ka] An HDAC ligand selected from, where R is [ka] [ka] This represents a connection to something.

[0209] In some embodiments, the TBM is [ka] A PPAR-γ ligand selected from, where R is [ka] [ka] This represents a connection to something.

[0210] In some embodiments, the TBM is [ka] Selected from, here [ka] It bonds to modifiable carbon, oxygen, nitrogen, or sulfur atoms.

[0211] In some embodiments, TBM is the following non-limiting example: [ka] [ka] [ka] A ligand selected from Abl, KRAS, SHP2, cRAF, MerTK, or PRMT5, where [ka] [ka] It bonds to modifiable carbon, oxygen, nitrogen, or sulfur atoms.

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

[0116] to

[0173] of WO 2016 / 197032, where the “linker” portion in WO 2016 / 197032 corresponds to the –L-group as defined and described herein.

[0213] In some embodiments, the TBM is [ka] [ka] A KRAS ligand selected from, where [ka] It bonds to modifiable carbon, oxygen, nitrogen, or sulfur atoms.

[0214] Exemplary compounds of the present invention are listed in Table 1 below. [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6]

[0215] In some embodiments, the above method uses the compounds listed in Table 1 above, or pharmaceutically acceptable salts thereof.

[0216] In some embodiments, the present invention provides a compound of formula I that is not one of the compounds shown in Table A-1 below.

[0217] [Table A1]

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

[0219] [Table A2-1] [Table A2-2] [Table A2-3] [Table A2-4]

[0220] In some embodiments, TBM is one of the compounds listed in Table 2 below, where [ka] [ka] It bonds to modifiable carbon, oxygen, nitrogen, or sulfur atoms.

[0221] Table 2-1 Table 2-2 Table 2-3 Table 2-4 Table 2-5 Table 2-6 Table 2-7 Table 2-8 Table 2-9 Table 2-10 Table 2-11 Table 2-12 Table 2-13 Table 2-14 Table 2-15 Table 2-16 Table 2-17 Table 2-18 Table 2-19 Table 2-20 Table 2-21 Table 2-22 Table 2-23 Table 2-24 Table 2-25 Table 2-26 Table 2-27 Table 2-28 Table 2-29 Table 2-30 Table 2-31 Table 2-32 Table 2-33 Table 2-34 Table 2-35 Table 2-36 Table 2-37 Table 2-38 Table 2-39 Table 2-40 Table 2-41 Table 2-42 Table 2-43 Table 2-44 Table 2-45 Table 2-46 Table 2-47 Table 2-48 Table 2-49 Table 2-50 Table 2-51 Table 2-52 Table 2-53 Table 2-54 Table 2-55 Table 2-56 Table 2-57 Table 2-58 Table 2-59 Table 2-60 Table 2-61 Table 2-62 Table 2-63 Table 2-64 Table 2-65 Table 2-66 Table 2-67 Table 2-68 Table 2-69 Table 2-70 Table 2-71 Table 2-72 Table 2-73 Table 2-74 Table 2-75 Table 2-76 Table 2-77 Table 2-78 Table 2-79 Table 2-80 Table 2-81 Table 2-82 Table 2-83 Table 2-84 Table 2-85 Table 2-86 Table 2-87 Table 2-88 Table 2-89 Table 2-90 Table 2-91 Table 2-92 Table 2-93 Table 2-94 Table 2-95 Table 2-96 Table 2-97 Table 2-98 Table 2-99 Table 2-100 Table 2-101 Table 2-102 Table 2-103 Table 2-104 Table 2-105 Table 2-106 Table 2-107 Table 2-108 Table 2-109 Table 2-110 Table 2-111 Table 2-112 Table 2-113 Table 2-114 Table 2-115 Table 2-116 Table 2-117 Table 2-118 Table 2-119 Table 2-120 Table 2-121 Table 2-122 Table 2-123 Table 2-124 Table 2-125 Table 2-126 Table 2-127 Table 2-128 Table 2-129

Table 2-130

Table 2-139

[0222] 5. Use, prescription, and administration Pharmaceutically acceptable compositions In another embodiment, the present invention provides compositions containing the compound of the present invention, or a pharmaceutically acceptable derivative thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle. The amount of the compound in the composition of the present invention is such that it is effective in measurably binding CRBN or its variants, and the targeted protein, in a biological sample or in a patient. In certain embodiments, the composition of the present invention is formulated for administration to a patient requiring such a composition. In some embodiments, the composition of the present invention is formulated for oral administration to a patient.

[0223] As used herein, the term “patient” means an animal, preferably a mammal, most preferably a human.

[0224] The term "pharmaceutically acceptable carrier, adjuvant, or vehicle" refers to a non-toxic carrier, adjuvant, or vehicle that does not impair the pharmacological activity of the compound formulated with it. Examples of pharmaceutically acceptable carriers, adjuvants, or vehicles that can be used in the compositions of this invention include ion exchangers, alumina, aluminum stearate, lecithin, serum proteins such as human serum albumin, buffering substances such as phosphates, glycine, sorbic acid, potassium sorbate, and saturated vegetable fatty acids. Examples include glyceride mixtures, water, electrolytes such as salts or protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, cellulosic substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylate, wax, polyethylene-polyoxypropylene-block polymer, polyethylene glycol, and wool fat.

[0225] "Pharmacologically acceptable derivative" means any non-toxic salt, ester, ester salt or other derivative of the compound of the present invention that can directly or indirectly provide the compound of the present invention or its inhibitory metabolite or residue when administered to a recipient.

[0226] As used herein, the term “its active metabolite or residue” means that the metabolite or residue is also a CRBN binder or a variant thereof, or the targeted protein or a variant thereof.

[0227] The compositions of the present invention can be administered orally, parenterally, by inhalation spray, topically, rectally, intranasally, oralally, vaginally, or by implantable reservoir. The term "parenteral," as used herein, includes subcutaneous, intravenous, intramuscular, intra-articular, intrabursal, intrasternal, intramedullary, intrahepatic, intrafocal, and intracranial injection or infusion techniques. Preferably, the compositions are administered orally, intraperitoneally, or intravenously. The sterile injectable forms of the compositions of this invention may be aqueous or oily suspensions. These suspensions may be formulated according to techniques known in the art using suitable dispersants or wetting agents and suspending agents. The sterile injectable preparations may also be sterile injectable solutions or suspensions in non-toxic, parenterally acceptable diluents or solvents, such as a solution in 1,3-butanediol. Acceptable vehicles and solvents that can be used include water, Ringer's solution, and isotonic sodium chloride solution. Furthermore, sterile fixing oils have conventionally been used as solvents or suspension media.

[0228] For this purpose, any non-irritating fixed oil containing synthetic monoglycerides or diglycerides can be used. Fatty acids, such as oleic acid and its glyceride derivatives, are useful in the preparation of injectable substances, particularly in their polyoxyethylated forms, as they are naturally pharmaceutically acceptable oils such as olive oil or castor oil. Solutions or suspensions of these oils may also contain long-chain alcohol diluents or dispersants, such as carboxymethylcellulose or similar dispersants, which are commonly used in the formulation of pharmaceutically acceptable dosage forms, including emulsions or suspensions. Other commonly used surfactants, such as Tween, Span, and other emulsifiers or bioavailability enhancers, which are commonly used in the manufacture of pharmaceutically acceptable solids, liquids, or other dosage forms, can also be used for formulation purposes.

[0229] The pharmaceutically acceptable compositions of this invention can be administered orally in any orally acceptable dosage form, including but not limited to capsules, tablets, aqueous suspensions, or liquids. For tablets for oral use, commonly used carriers include lactose and corn starch. Lubricants such as magnesium stearate are also typically added. For oral administration in capsule form, lactose and dried corn starch are useful diluents. When aqueous suspensions are required for oral use, the active ingredient is combined with emulsifiers and suspending agents. Certain sweeteners, flavoring agents, or colorants may also be added, if desired.

[0230] Alternatively, the pharmaceutically acceptable compositions of this invention can be administered in the form of suppositories for rectal administration. These are solid at room temperature but liquid at rectal temperature, however This can be prepared by mixing the drug with a suitable non-irritating excipient that dissolves in the rectum to release the drug. Examples of such materials include cocoa butter, beeswax, and polyethylene glycol.

[0231] The pharmaceutically acceptable compositions of this invention can also be administered topically, particularly when the target of treatment includes areas or organs that are easily accessible by topical application, such as diseases of the eyes, skin, or lower intestines. Suitable topical formulations can be readily prepared for each of these areas or organs.

[0232] Topical application to the lower intestinal tract may be performed with rectal suppositories (see above) or suitable enema formulations. Topical transdermal patches may also be used.

[0233] For topical application, the pharmaceutically acceptable compositions provided may be formulated into suitable ointments containing the active ingredient suspended or dissolved in one or more carriers. Carriers for topical administration of the compounds of this invention include, but are not limited to, mineral oil, liquid paraffin, white petrolatum, propylene glycol, polyoxyethylene, polyoxypropylene compounds, emulsifying wax, and water. Alternatively, the pharmaceutically acceptable compositions provided may be formulated into suitable lotions or creams containing the active ingredient suspended or dissolved in one or more pharmaceutically acceptable carriers. Suitable carriers include, but are not limited to, mineral oil, sorbitan monostearate, polysorbate 60, cetyl ester wax, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol, and water.

[0234] For ophthalmic use, the pharmaceutically acceptable compositions provided may be formulated as a finely powdered suspension in isotonic pH-adjusted sterile saline, or preferably as a liquid in isotonic pH-adjusted sterile saline with or without a preservative such as benzylalkonium chloride. Alternatively, the pharmaceutically acceptable compositions for ophthalmic use may be formulated as an ointment such as petrolatum.

[0235] The pharmaceutically acceptable compositions of this invention can also be administered by nasal aerosol or inhalation. Such compositions may be prepared according to techniques well known in the art of pharmaceutical formulations and prepared as liquids in saline using benzyl alcohol or other suitable preservatives, absorption enhancers to enhance bioavailability, carbon fluoride, and / or other conventional solubilizers or dispersants.

[0236] Most preferably, the pharmaceutically acceptable compositions of this invention are formulated for oral administration. Such formulations may be administered with or without food. In some embodiments, the pharmaceutically acceptable compositions of this invention are administered without food. In other embodiments, the pharmaceutically acceptable compositions of this invention are administered with food.

[0237] The amount of the compound of the present invention, which may be combined with a carrier material to produce a single dosage form, will vary depending on the host being treated and the specific administration method. Preferably, the provided compositions should be formulated so that a dosage of the compound between 0.01 and 100 mg per kg of body weight per day can be administered to a patient receiving these compositions.

[0238] It should be understood that the specific dosage and treatment regimen for any particular patient may vary depending on various factors, including the activity of the specific compound used, age, weight, overall health, sex, diet, administration time, elimination rate, drug combination, and the judgment of the treating physician and the severity of the specific disease being treated. The amount of the compound of the present invention in the composition is It will also vary depending on the specific compounds in the substance. Use of compounds and pharmaceutically acceptable compositions

[0239] Described herein are compositions and methods relating to the surprising and unexpected discovery that an E3 ubiquitin ligase protein (e.g., cereblon) ubiquitinates a target protein once it is brought into close proximity to the target protein by a bifunctional or chimeric construct that binds the E3 ubiquitin ligase protein and the target protein. Accordingly, the present invention provides such compounds and compositions comprising an E3 ubiquitin ligase binding moiety ("UBM") bound to a protein target binding moiety ("TBM"), thereby ubiquitinating a selected target protein, which results in the degradation of the target protein by the proteasome.

[0240] The compounds and compositions described herein are generally useful for the modulation of targeted ubiquitination, particularly with respect to various polypeptides and other proteins that are degraded and / or otherwise inhibited. In some embodiments, proteins inhibited by the compounds and methods of the present invention include those listed in paragraph

[0181] .

[0241] The compounds and compositions described herein exhibit broad pharmacological activity and are compatible with the degradation / inhibition of targeted polypeptides.

[0242] Therefore, compounds that bind to CRBN, particularly those with high selectivity in preference to E3 ligase, are beneficial. Such compounds should deliver a pharmacological response that favorably treats one or more of the conditions described herein without side effects associated with E3 ligase inhibition.

[0243] Although CRBN binders are known in the art, there is still a need to provide novel binders with more effective or advantageous pharmaceutically relevant properties. For example, compounds with increased activity, higher selectivity in preference to other E3 ligases, and ADMET (absorption, distribution, metabolism, excretion, and / or toxicity) properties. Therefore, in some embodiments, the present invention provides CRBN binders that exhibit higher selectivity in preference to other E3 ligases.

[0244] The inhibitory activity of the compounds used in this invention against CRBN or its variants can be assayed in vitro, in vivo, or in cell lines. In vitro assays include those that determine the subsequent functional consequences of activated CRBN or its variants, or inhibition of its activity. Alternative in vitro assays quantify the ability of a compound to bind to CRBN. Binding can be measured by radiolabeling the compound before binding, isolating the compound / CRBN complex, and determining the amount of bound radiolabeling. Alternatively, the binding of a compound can be determined by performing competitive experiments in which a novel compound is incubated with CRBN bound to a known radioligand. Representative in vitro and in vivo assays useful for assaying CRBN conjugates are, for example, those described and disclosed in Boichenko et al. J.Med.Chem. (2016) 59, 770-774 and Iconomou and Saunders Biochemical Journal (2016) 473, 4083-4101, each of which is incorporated herein by reference in whole. Detailed conditions for assaying compounds used as conjugates for CRBN or its variants in this invention are described in the following examples.

[0245] The term "ubiquitin ligase" refers to a specific enzyme that targets substrate proteins for degradation. This refers to a family of proteins that facilitate the transfer of ubiquitin to substrate proteins. For example, cereblon is an E3 ubiquitin ligase protein that, either alone or in combination with E2 ubiquitin-conjugating enzymes, causes ubiquitin to bind to lysine on target proteins, and then targets specific protein substrates for degradation by the proteasome. Thus, E3 ubiquitin ligases, either alone or in complex with E2 ubiquitin-conjugating enzymes, are responsible for the transfer of ubiquitin to targeted proteins. Generally, ubiquitin ligases are involved in polyubiquitination, where a second ubiquitin molecule binds to a first ubiquitin molecule, a third ubiquitin molecule binds to a second ubiquitin molecule, and so on. Polyubiquitination marks proteins for degradation by the proteasome. However, there are some ubiquitination events that are limited to monoubiquitination, in which case only one ubiquitin molecule is attached to the substrate molecule by this ubiquitin ligase. Monoubiquitinated proteins are not targeted by the proteasome for degradation; instead, their location or function in the cell can be altered, for example, by binding to other proteins that have domains capable of binding ubiquitin. Further complicating matters, different lysines on ubiquitin can be targeted by a single E3 to form chains. The most common lysine is Lys48 on ubiquitin chains, which is used to create polyubiquitin recognized by the proteasome.

[0246] As used herein, the terms “treatment,” “treat,” and “treating” refer to the reversal, reduction, delay of onset, or inhibition of progression of a disease or disorder, or one or more of its symptoms, as described herein. In some embodiments, treatment may be administered after the onset of one or more symptoms. In other embodiments, treatment may be administered in the absence of symptoms. For example, treatment may be administered to a susceptible individual before the onset of symptoms (e.g., taking into account the history of the symptoms and / or genetic or other susceptibility factors). Treatment may also be continued after the symptoms have subsided, for example, to prevent or delay the recurrence of those symptoms.

[0247] This specification provides therapeutic compositions described herein for inducing the degradation of a target protein for the treatment or mitigation of a disease (e.g., cancer). In a particular further embodiment, this disease is multiple myeloma. Thus, in another aspect, this specification provides a method for ubiquitinating / degrading a target protein within a cell. In a particular embodiment, this method comprises the step of administering a bifunctional compound described herein, which comprises a UBM and a TBM linked via a linker moiety, as otherwise described herein, for example, the UBM is bound to the TBM, and the UBM recognizes a ubiquitin pathway protein (e.g., a ubiquitin ligase, preferably an E3 ubiquitin ligase, e.g., cereblon), and the TBM recognizes a target protein, and as a result the target protein is placed near the ubiquitin ligase, degradation of the target protein occurs, thus resulting in the degradation of the target protein and / or inhibition of its effects, and regulation of protein levels. The control of protein levels provided by the present invention provides treatment for a disease or condition regulated via a target protein by reducing the level of the target protein within a cell, for example, within a patient's cell. In certain embodiments, the method comprises the step of administering an effective amount of a compound described herein, including, optionally, a pharmaceutically acceptable excipient, carrier, adjuvant, another bioactive agent, or a combination thereof.

[0248] In further embodiments, this specification provides a method for treating or alleviating a disease, disorder or its symptoms in a subject or patient, the method comprising administering to the subject in need an effective amount (e.g., a therapeutically effective amount) of a compound or salt form thereof described herein, and a pharmaceutically acceptable excipient, carrier, adjuvant, or other bioactive agent. The procedure comprises administering a composition containing these combinations, wherein the composition is effective in treating or alleviating the disease or disorder or its symptoms in the subject.

[0249] In another aspect, this specification provides a method for identifying the effect of compounds according to the present invention on the degradation of a target protein in a biological system.

[0250] In another embodiment, the present invention relates to a method for treating a human patient whose medical condition or state requires regulation via a protein, wherein the degradation of this protein produces a therapeutic effect in the patient, and the method comprises the step of administering to the patient in need an effective amount of a compound according to the present invention, in combination as necessary with another bioactive agent. The medical condition or state may be a disease caused by a microbial factor or other harmful negative factor (e.g., a virus, bacteria, fungi, protozoa or other pathogens), or a medical condition caused by the overexpression of a protein that results in the medical condition and / or state.

[0251] Conditions that can be treated using the compounds according to the present invention include, for example, asthma, autoimmune diseases such as multiple sclerosis, various cancers, ciliopathies, cleft palate, diabetes, heart disease, hypertension, inflammatory bowel disease, intellectual disability, mood disorders, obesity, refractive errors, recurrent miscarriage, Angelman syndrome, Canavan disease, celiac disease, Charcot-Marie-Tooth disease, cystic fibrosis, Duchesne muscular dystrophy, hemochromatosis, hemophilia, Klinefelter syndrome, neurofibromatosis, phenylketonuria, polycystic kidney disease, Prader-Willi syndrome (PKD1) or PKD4 (PKD2), sickle-cell disease, Ty-Sachs disease, and Turner syndrome.

[0252] Further medical conditions or states that can be treated with the compounds according to the present invention include Alzheimer's disease, amyotrophic lateral sclerosis (Lou Gehrig's disease), anorexia nervosa, anxiety disorders, atherosclerosis, attention deficit hyperactivity disorder, autism, bipolar depression, chronic fatigue syndrome, chronic obstructive pulmonary disease, Crohn's disease, coronary heart disease, dementia, depression, type 1 diabetes, type 2 diabetes, epilepsy, Guillain-Barré syndrome, irritable bowel syndrome, lupus, metabolic syndromes, multiple sclerosis, myocardial infarction, obesity, obsessive-compulsive disorder, panic disorder, Parkinson's disease, psoriasis, rheumatoid arthritis, sarcoidosis, schizophrenia, stroke, thromboangiitis obliterans, Tourette's syndrome, and vasculitis.

[0253] Further conditions or states that can be treated with the compounds according to the present invention include, in particular, aceruloplasminemia, type II chondrodysplasia, chondrodysplasia, acrocephaly, type 2 Gaucher disease, acute intermittent porphyria, Canavan disease, adenomatous polyposis, ALA dehydratase deficiency, adenylosuccinate lyase deficiency, adrenogenital syndrome, adrenocerebral white matter dystrophy, ALA-D porphyria, ALA dehydratase deficiency, alkaptonuria, Alexander disease, alkaptonuric ochronosis, α1-antitrypsin deficiency, α-1 proteinase inhibitors, emphysema, and amyotrophic lateral sclerosis. Alström syndrome, Alexander disease, amelodysplasia, ALA dehydratase deficiency, Anderson-Fabry disease, androgen resistance syndrome, anemia, widespread trunk keratogenic hemangioma, retinal hemangioma (von Hippel-Lindau disease), Apert syndrome, arachnidactyly (Marfan syndrome), Stickler syndrome, congenital polyarthralasia (Ehlers-Danlow syndrome # polyarthralasia type), ataxia vasodilator, Rett syndrome, primary pulmonary hypertension, Sandhoff disease, neurofibromatosis type II, Behle-Stevenson gyruform scalp syndrome, Mediterranean fever, familial, Benjamin (Benj amin syndrome, β-thalassemia, bilateral acoustic neurofibromatosis (Type II neurofibromatosis), factor V Leiden thrombophilia, Bloch-Salsberger syndrome (incontinentia pigmenti), Bloom syndrome, X-linked sideroblastic anemia, Bonnewi-Ulrich syndrome (Turner syndrome), Brunneville disease (tuberous sclerosis), prion disease, Birt-Hogg-Duvet syndrome, osteogenesis imperfecta (Brittle Bone disease (osteogenesis imperfecta), broad thumb-hallux syndrome (Rubinstein-Taey syndrome), bronzed cirrhosis (hemochromatosis), spinal and bulbar muscular atrophy (Kennedy disease), Bürger-Grütz syndrome (lipoprotein lipase deficiency), chronic granulomatous disease (CGD), flexor limb dysplasia, biotinidase deficiency, cardiomyopathy (Noonan syndrome), cat-like meowing, CAVD (congenital absence of the vas deferens), Caylor's heart-face syndrome (CBAVD), CEP (congenital hematopoietic porphyria), cystic fibrosis, congenital thyroid dysfunction, chondrodysplasia (chondrodysplasia), chondrodysplasia with sensorineural hearing loss, Lesch-Nyhan syndrome Galactosemia, Ehlers-Danloe syndrome, thanatophoric dysplasia, Coffin-Lowry syndrome, Cockaine syndrome, (familial adenomatous polyposis), congenital hematopoietic porphyria, congenital heart disease, methemoglobinemia / congenital methemoglobinemia, chondrodysplasia, X-linked sideroblastic anemia, connective tissue disease, conotibial stump anomalous facies syndrome, Cooley's anemia (β-thalassemia), copper storage disorder (Wilson's disease), copper transport disorder (Menkes disease), hereditary coproporphyria, Cowden syndrome, craniofacial dysostosis Dysarthrosis (Cruzon syndrome), Creutzfeldt-Jakob disease (prion disease), Cockaine syndrome, Cowden syndrome, Curschmann-Batten-Steinert syndrome (myotonic dystrophy), Beare-Stevenson cutis gyrata syndrome, primary hyperoxaluria, spondyloepiphyseal dysplasia (Strudwick type), muscular dystrophy, Duchesne and Becker types (DBMD), Usher syndrome, degenerative neurological diseases (including de Grouchy syndrome and Desgerine-Sottas syndrome), developmental disorders, distal spinal muscular atrophy.Type V, androgen resistance syndrome, diffuse globoid body sclerosis (Clavier's disease), DiGeorge syndrome, dihydrotestosterone receptor deficiency, androgen resistance syndrome, Down syndrome, dwarfism, erythroblastic protoporphyria, erythrocyte 5-aminolevulinic acid synthetase deficiency, hematopoietic porphyria, erythroblastic protoporphyria, erythropoietic uroporphyria, Friedreich's ataxia, familial paroxysmal polyserositis, late-onset cutaneous porphyria, familial pressure-sensitive neuropathy Neuropathy, primary pulmonary hypertension (PPH), pancreatic fibrocystic disease, fragile X syndrome, galactosemia, hereditary brain disorder, giant cell hepatitis (neonatal hemochromatosis), Grenblatt-Strandbury syndrome (pseudoxanthoma elastica), Günther's disease (congenital hematopoietic porphyria), hemochromatosis, Hallgren's syndrome, sickle cell anemia, hemophilia, hepatic hematopoietic porphyria (HEP), Hippel-Lindau disease (von Hippel-Lindau disease), Huntington's disease, Hutchinson-Gilford progeria syndrome Syndrome (progeria), androgen excess, hypochondrosis, hypochromic anemia, immune system disorders (X-linked severe combined immunodeficiency, Insley-Astley syndrome, Jackson-Weiss syndrome, Joubert syndrome, Lesch-Nyhan syndrome, Jackson-Weiss syndrome), kidney disease (hyperoxaluria), Klinefelter syndrome, Kniist dysplasia, malformed dementia, Langer-Saldino achondroplasia, ataxia vasodilator, Lynch syndrome, lysyl hydroxylase deficiency, Machado-Joseph disease, metabolic disorders (Kniist dysplasia), Marfan syndrome, motor disorders, Mowat-Wilson syndrome, cystic fibrosis, Muenke syndrome, multiple neurofibromas, Nance-Insley syndrome, Nance-Sweeney chondrodysplasia, Niemann-Pick disease, Noack syndrome (Pfeiffer syndrome), Osler-Weber-Landu disease, Peutz-Jeggers syndrome, polycystic kidney disease, multiple fibrous dysplasia (McKune-Albright syndrome), Peutz-Jeggers syndrome, Prader-Labhart-Willi syndrome, hemochromatosis, primary hyperuricemia syndrome (Lesch-Nyhan syndrome), primary pulmonary hypertension, primary senile regression Dementia palsy, prion disease, progeria (Hutchinson-Gilford progeria syndrome), progressive chorea, chronic hereditary disease (Huntington's disease), progressive muscular atrophy, spinal muscular atrophy, propionic aciduria, protoporphyria, proximal myotonic dystrophy, pulmonary hypertension, PXE (pseudoxanthoma elastica), Rb (retinoblastoma), neurofibromatosis type I, relapsing polyserositis, retinal disorders, retinoblastoma, Rett syndrome, RFALS type 3, Ricker syndrome, Riley-Day syndrome, Lucy-Levi syndrome, severe chondrodysplasia with growth retardation and acanthosis nigricans (SADDAN), Lie-Fraumeni syndrome, sarcoma, mammary gland, leukemia, and adrenal (SBLA) syndrome, tuberous sclerosis sclerosis)), SDAT, congenital SED (congenital spondylo-epiphyseal dysplasia), SED Strudwick (spondylo-epiphyseal dysplasia, Strudwick type), SEDc (congenital spondylo-epiphyseal dysplasia) SEMD, Strudwick type (spondylo-epiphyseal dysplasia),Strudwick type, Sprinzen syndrome, cutaneous pigmentation disorder, Smith-Lemley-Opitz syndrome, South African genetic porphyria (atypical porphyria), infantile-onset ascending hereditary spastic paralysis, speech and communication disorders, sphingolipidosis, Ty-Sachs disease, spinocerebellar ataxia, Stickler syndrome, stroke, androgen resistance syndrome, tetrahydrobiopterin deficiency, β-thalassemia, thyroid disorders, sausage-like neuropathy (hereditary neuropathy with susceptibility to compressive paralysis), Tretcher-Collins syndrome, XXX syndrome (Triplo X syndrome) (triple X syndrome), chromosome 21 (Down syndrome), chromosome 1X, VHL syndrome (von Hippel-Lindau disease), visual impairment and blindness (Alström syndrome), Florik's disease (Vrolik Examples include Waardenburg syndrome, Warburg Sjo Fledelius syndrome, Weissenbacher-Zweymueller syndrome, Wolf-Hirschhorn syndrome, Wolff Periodic disease, Weissenbacher-Zweymueller syndrome, and xeroderma pigmentosum.

[0254] The terms “neoplasia” or “cancer” are used herein to refer to the formation and growth of malignant or cancerous neoplasms, which are pathological processes resulting from the formation and growth of abnormal tissues that often grow faster than normal by cell proliferation and continue to grow even after the stimulus that initiated this new growth has ceased. Malignant neoplasms exhibit a partial or complete loss of the organizational and functional emphasis of structure compared to normal tissue, and most invade surrounding tissues, metastasize to several locations, and are prone to recurrence after attempts at elimination, leading to death of the patient if not adequately treated. As used herein, the term neoplasia is used to describe all cancerous conditions and encompasses or includes pathological processes related to malignant hematogenic, cytotoxic, and solid tumors. Exemplary cancers that can be treated with the compounds of the present invention, either alone or in combination with at least one further anticancer agent, include squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, hepatocellular carcinoma, and renal cell carcinoma; bladder, intestine, breast, neck, colon, esophagus, head, and kidney. Cancers of the organs, liver, lungs, neck, ovaries, pancreas, prostate, and stomach; leukemia; benign and malignant lymphomas, especially Burkitt lymphoma and non-Hodgkin lymphoma; benign and malignant melanomas; myeloproliferative disorders; sarcomas (Ewing's sarcoma, angiosarcoma, Kapose's sarcoma, liposarcoma, myosarcoma, peripheral neuroepithelioma, synovial sarcoma, glioma, glioastrocytoma, oligodendroglioma, ependymal cell tumor, glioblastoma) Examples of cancers that can be treated with the compounds of the present invention include neuroblastoma, gangliocytoma, ganglioglioma, medulloblastoma, pineal tumor, meningioma, meningiosarcoma, neurofibroma, and schwannoma; intestinal cancer, breast cancer, prostate cancer, cervical cancer, uterine cancer, lung cancer, ovarian cancer, testicular cancer, thyroid cancer, glioastrocytoma, esophageal cancer, pancreatic cancer, gastric cancer, liver cancer, colon cancer, melanoma; carcinosarcoma, Hodgkin's disease, Wilms' tumor, and teratoma. Further cancers that can be treated with the compounds of the present invention include, for example, T-cell acute lymphoblastic leukemia (T-ALL), T-lineage lymphoblastic lymphoma (T-LL), peripheral T-cell lymphoma, adult T-cell leukemia, pre-B ALL, pre-B lymphoma, large B-cell lymphoma, Burkitt lymphoma, B-cell ALL, Philadelphia chromosome-positive ALL, and Philadelphia chromosome-positive CML.

[0255] In some embodiments, the present invention provides a method for treating one or more disorders, wherein the disorder is selected from autoimmune disorders, inflammatory disorders, proliferative disorders, endocrine disorders, neurological disorders, and transplant-related disorders, and the method comprises the step of administering to a patient in need a pharmaceutical composition comprising an effective amount of the compound of the present invention or a pharmaceutically acceptable salt thereof.

[0256] In some embodiments, the compounds of the present invention are A1BG, A1CF, A2M, A2ML1, and A3GALT2. ,A4GALT, A4GNT, AAAS, AACS, AADAC, AADACL2, AADACL3, AADACL4, AADAT, AAED1, AAGAB, AAK1, AAMDC, AAMP, AANAT, AAR2, AARD, AARS, AARS2, AARSD1, AASDH, AASDHPPT, AASS, AATF, AATK, AATK-AS1, ABAT, ABCA1, ABCA10, ABCA12, ABCA13, ABCA2, ABCA3, ABCA4, ABCA5, ABCA6, ABCA7, ABCA8, ABCA9, ABCB1, ABCB10, ABCB11, ABCB4, ABCB5, ABC B6、ABCB7、ABCB8、ABCB9、ABCC1、ABCC10、ABCC11、ABCC12、ABCC2、ABCC3、ABCC4、ABCC5、ABCC6、ABCC8、ABCC9、ABCD1、ABCD2、ABCD3、ABCD4、ABCE1、ABCF1、ABCF2、ABCF3 ABCG1、ABCG2、ABCG4、ABCG5、ABCG8、ABHD1、ABHD10、ABHD11、ABHD12、ABHD12B、ABHD13、ABHD14A、ABHD14A-ACY1、ABHD14B、ABHD15、ABHD16A、ABHD16B、ABHD17A、ABHD17B 、ABHD17C、ABHD18、ABHD2、ABHD3、ABHD4、ABHD5、ABHD6、ABHD8、ABI1、ABI2、ABI3、ABI3BP、ABL1、ABL2、ABLIM1、ABLIM2、ABLIM3、ABO、ABR、ABRA、ABRACL、ABRAXAS1、ABRAXAS2、ABT1、ABTB1、ABTB2、AC001226.2、AC002094.3、AC002115.2、AC002310.4、AC002310.5、AC002429.2、AC002985.1、AC002996.1、AC003002.1、AC003002.2、AC003002.3、AC003002.4、AC003005.1、AC003006.1、AC003688.1、AC004076.1、AC004080.3、AC004223.3、AC004233.2、AC004556.1、AC004691.2、AC004706.4、AC004754.1、AC004805.1、AC004832.3、AC004922.1、AC004997.1、AC005020.2、AC005041.1、AC005154.6、AC005258.1、AC005324.3、AC005324.4、AC005520.1、AC005551.1、AC005670.2、AC005697.1、AC005702.2、AC005726.2、AC005779.2、AC005832.4、AC005833.1、AC005833.3、AC005837.2、AC005841.2、AC005885.1、AC005943.1、AC006030.1、AC006254.1、AC006269.1、AC006449.4、AC006486.1、AC006538.2、AC006978.2、AC007040.2、AC007192.1、AC007240.1、AC007325.1、AC007325.2、AC007325.4、AC007326.4、AC007375.2、AC007383.6、AC007537.5、AC007731.5、AC007906.2、AC007998.2、AC008073.3、AC008162.2、AC008393.2、AC008403.1、AC008481.3、AC008537.1、AC008560.1、AC008575.1、AC008575.2、AC008687.1、AC008687.4、AC008687.8、AC008695.1、AC008735.6、AC008750.8、AC008758.1、AC008758.4、AC008758.5、AC008758.6、AC008763.2、AC008763.3、AC008764.1、AC008764.4、AC008770.2、AC008770.3、AC008878.1、AC008878.2、AC008878.3、AC008982.1、AC008982.3、AC009014.1、AC009086.2、AC009119.2、AC009122.1、AC009133.6、AC009163.2、AC009163.4、AC009286.3、AC009336.2、AC009477.2、AC009690.1、AC009690.3、AC009779.3、AC010132.3、A. C010255.3、AC010319.2、AC010323.1、AC010325.1、AC010326.2、AC010327.1、AC010422.3、AC010422.5、AC010422.6、AC010463.1、AC010487.3、AC010522.1、AC010531.1、AC010542.3、AC010547.4、AC010547.5、AC010615.4、AC010616.1、AC010619.1、AC010646.1、AC010724.2、AC011005.1、AC011043.1、AC011043.2、AC011195.2、AC011295.1、AC011346.1、AC011448.1、AC011452.1、AC011455.3、AC011455.4、AC011462.1、AC011473.4、AC011479.1、AC011498.4、AC011499.1、AC011511.1、AC011511.4、AC011530.1、AC011604.2、AC011841.1、AC012184.2、AC012254.2、AC012309.1、AC012314.1、AC012314.10、AC012314.11、AC012314.12、AC012314.4、AC012314.5、AC012314.6、AC012314.8、AC012531.3、AC012651.1、AC013269.1、AC013271.1、AC013394.1、AC013470.2、AC015688.5、AC015802.6、AC015813.2、AC017081.3、AC017081.4、AC017081.5、AC017083.4、AC018512.1、AC018523.2、AC018554.3、AC018630.6、AC018709.1、AC018755.2、AC018793.1、AC018793.2、AC018793.3、AC018793.4、AC018793.5、AC019117.3、AC020636.2、AC020909.1、AC020914.1、AC020915.1、AC020915.2、AC020915.6、AC020922.1、AC020934.3、AC021072.1、AC022016.2、AC022167.5、AC022335.1、AC022384.1、AC022400.6、AC022826.2、AC023055.1、AC023491.2、AC023509.3、AC024592.3、AC024940.1、AC024940.6、AC025165.3、AC025263.2、AC025283.2、AC025287.4、AC025594.2、AC026369.8、AC026398.1、AC026461.4、AC026464.1、AC026464.3、AC026464.4、AC026786.1、AC026954.2、AC027796.3、AC034102.2、AC036214.3、AC037459.1、AC037482.2、AC037482.3、AC040162.1、AC040162.4、AC044810.8、AC046185.1、AC048338.1、AC051649.2、AC053481.5、AC055811.2、AC058822.1、AC064853.2、AC064853.3、AC064853.4、AC064853.5、AC064853.6、AC067968.1、AC068234.1、AC068533.4、AC068547.1、AC068580.4、AC068631.2、AC068775.1、AC068775.2、AC068790.8、AC068896.1、AC068946.1、AC068987.5、AC069257.3、AC069368.1、AC069503.2、AC069544.2、AC072022.1、AC073082.1、AC073111.3、AC073111.5、AC073264.3、AC073508.2、AC073610.2、AC073610.3、AC073612.1、AC073896.1、AC074143.1、AC078927.1、AC079325.2、AC079447.1、AC079594.2、AC083800.1、AC083902.2、AC084337.2、AC087289.3、AC087498.1、AC087632.1、AC090004.1、AC090227.1、AC090360.1、AC090527.2、AC090958.3、AC091167.3、AC091167.7、AC091167.8、AC091304.7、AC091491.1、AC091551.1、AC091959.3、AC091980.2、AC092017.3、AC092042.3、AC092073.1、AC092111.3、AC092143.1、AC092329.3、AC092442.1、AC092587.1、AC092647.5、AC092718.3、AC092718.8、AC092821.1、AC092824.3、AC092835.1、AC093155.3、AC093227.3、AC093423.3、AC093525.1、AC093525.2、AC093668.1、AC093762.1、AC093762.2、AC093762.3、AC093899.2、AC096582.3、AC096887.1、AC097372.1、AC097495.1、AC097637.1、AC097662.2、AC098484.3、AC098650.1、AC098850.4、AC099329.3、AC099489.1、AC099518.3、AC099811.2、AC099850.2、AC100868.1、AC104109.3、AC104151.1、AC104304.1、AC104452.1、AC104532.1、AC104534.3、AC104581.1、AC104581.3、AC104662.2、AC104836.1、AC105001.2、AC105052.1、AC106774.10、AC106774.5、AC106774.6、AC106774.7、AC106774.8、AC106774.9、AC106782.1、AC106886.5、AC107871.1、AC108488.2、AC108750.1、AC108941.2、AC109583.3、AC110275.1、AC112229.3、AC112484.1、AC113189.6、AC113189.9、AC113331.2、AC113554.2、AC114296.1、AC114490.2、AC115220.1、AC116366.3、AC116565.1、AC117457.1、AC118470.1、AC118553.2、AC119396.1、AC119674.2、AC120057.3、AC120114.5、AC124312.1、AC126755.2、AC127537.5、AC127537.6、AC127537.8、AC129492.3、AC131097.2、AC131160.1、AC133551.1、AC133555.3、AC134669.2、AC134772.2、AC135050.2、AC135068.1、AC135068.2、AC135 068.3、AC135068.8、AC135178.2、AC135586.2、AC136352.3、AC136352.4、AC136428.1、AC136612.1、AC 136616.1, AC136616.2, AC136616.3, AC137834.1, AC138517.2, AC138647.1, AC138696.1, AC138811.2, AC138894.1, AC138969.1, AC139530.2, AC139677.1, AC139677.2, AC140504.1, AC141272.1, AC1423 91.1, AC142525.4, AC145029.2, AC145212.1, AC145212.2, AC171558.1, AC171558.3, AC171558.5, AC171558.6, AC187653.1, AC207056.1, AC209232.1, AC209539.2, AC210544.1, AC213203.1, AC229888.1 AC229888.10, AC229888.2, AC229888.3, ​​AC229888.4, AC229888.5, AC229888.6, AC229888.7, AC229888.8, AC229888.9, AC233282.1, AC233282.2, AC233723.1, AC233724.12, AC233724.16, AC233724.1. 7, AC233724.18, AC233724.19, AC233724.20, AC233724.21, AC233724.6, AC233755.1, AC233755.2, AC233992.2, AC234301.1, AC234301.3, AC234635 .1、AC234635.3、AC234635.4、AC234635.5、AC236040.1、AC239612.1、AC23 9618.1、AC239618.2、AC239618.3、AC239618.4、AC239618.5、AC239618.6、A C239618.7、AC239618.9、AC239799.1、AC240274.1、AC241401.1、AC241409 .2、AC241410.1、AC241556.3、AC241556.4、AC241640.1、AC241640.2、AC24 1640.4, AC242528.1, AC242528.2, AC243547.3, AC243733.1, AC243734.1, AC243756.1, AC243790.1, AC243967.1, AC244196.1, AC244196.2, AC244196 .3、AC244196.4、AC244196.5、AC244197.3、AC244216.4、AC244216.5、AC24 4226.1、AC244226.2、AC244472.1、AC244472.2、AC244472.3、AC244472.4、 AC244472.5、AC244489.1、AC244489.2、AC244517.10、AC244517.6、AC2450 33.1、AC245034.2、AC245078.1、AC245088.2、AC245088.3、AC245369.1、AC2 45369.2, AC245369.3, AC245369.4, AC245369.6, AC245427.1, AC245427.3, AC245427.4, AC245427.5, AC245427.6, AC245427.7, AC245427.8, AC24542 7.9, AC245748.1, AC247036.3, AC247036.4, AC247036.5, AC247036.6, AC254560.1, AC254788.1, AC254788.2, AC254952.1, AC255093.3, AC255093.5AC256236.1、AC256236.2、AC256236.3、AC256300.2、AC256309.2、AC270107.1、AC270107.10、AC270107.12、AC270107.2、AC270107.3、AC270107.4、AC270107.5、AC270107.7、AC270107.8、AC270107.9、AC270227.1、AC270306.4、AC275455.2、ACAA1、ACAA2、ACACA、ACACB、ACAD10、ACAD11、ACAD8、ACAD9、ACADL、ACADM、ACADS、ACADSB、ACADVL、ACAN、ACAP1、ACAP2、ACAP3、ACAT1、ACAT2、ACBD3、ACBD4、ACBD5、ACBD6、ACBD7、ACCS、ACCSL、ACD、ACE、ACE2、ACER1、ACER2、ACER3、ACHE、ACIN1、ACKR1、ACKR2、ACKR3、ACKR4、ACLY、ACMSD、ACO1、ACO2、ACOD1、ACOT1、ACOT11、ACOT12、ACOT13、ACOT2、ACOT4、ACOT6、ACOT7、ACOT8、ACOT9、ACOX1、ACOX2、ACOX3、ACOXL、ACP1、ACP2、ACP4、ACP5、ACP6、ACP7、ACPP、ACR、ACRBP、ACRV1、ACSBG1、ACSBG2、ACSF2、ACSF3、ACSL1、ACSL3、ACSL4、ACSL5、ACSL6、ACSM1、ACSM2A、ACSM2B、ACSM3、ACSM4、ACSM5、ACSM6、ACSS1、ACSS2、ACSS3、ACTA1、ACTA2、ACTB、ACTBL2、ACTC1、ACTG1、ACTG2、ACTL10、ACTL6A、ACTL6B、ACTL7A、ACTL7B、ACTL8、ACTL9、ACTN1、ACTN2、ACTN3、ACTN4、ACTR10、ACTR1A、ACTR1B、ACTR2、ACTR3、ACTR3B、ACTR3C、ACTR5、ACTR6、ACTR8、ACTRT1、ACTRT2、ACTRT3、ACVR1、ACVR1B、ACVR1C、ACVR2A、ACVR2B、ACVRL1、ACY1、ACY3、ACYP1、ACYP2、AD000671.1、AD000671.2、ADA、ADA2、ADAD1, ADAD2, ADAL, ADAM10, ADAM11, ADAM12, ADAM15, ADAM17, ADAM18, ADAM19, ADAM2, ADAM20, ADAM21, ADAM22, ADAM23, ADAM28, ADAM29, ADAM30, ADAM32, ADAM33, ADAM7, ADAM8, ADAM9, ADAMDEC1, ADAMTS1, ADAMTS10, ADAMTS12, ADAMTS13, ADAMTS14, ADAMTS15, ADAMTS16, ADAMTS17, ADAMTS18, ADAMTS 19、ADAMTS2、ADAMTS20、ADAMTS3、ADAMTS4、ADAMTS5、ADAMTS6、ADAMTS7、ADAMTS8、ADAMTS9、ADAMTSL1、ADAMTSL2、ADAMTSL3、ADAMTSL4、ADAMTSL5、ADAP1、ADAP2、ADAR、ADARB1、ADARB2、ADAT1、ADAT2、ADAT3、ADCK1、ADCK2、ADCK5、ADCY1、ADCY10、ADCY2、ADCY3、ADCY4、ADCY5、ADCY6、ADCY7、ADCY8、ADCY9、 ADCYAP1、ADCYAP1R1、ADD1、ADD2、ADD3、ADGB、ADGRA1、ADGRA2、ADGRA3、ADGRB1、ADGRB2、ADGRB3、ADGRD1、ADGR2、ADGRE1、ADGRE2、ADGRE3、ADGRE5、ADGRE1 GRF1、ADGRF2、ADGRF3、ADGRF4、ADGRF5、ADGRG1、ADGRG2、ADGRG3、ADGRG4、ADGRG5、ADGRG6、ADGRG7、ADGRL1、ADGRL2、ADGRL3、ADGRL4、ADGRV1、ADH1A、ADGRL1 H1B、ADH1C、ADH4、ADH5、ADH6、ADH7、ADHFE1、ADI1、ADIG、ADIPOQ、ADIPOR1、ADIPOR2、ADIRF、ADK、ADM、ADM2、ADM5、ADNP、ADNP2、ADO、ADORA1、ADORA2A、 ADORA2B、ADORA3、ADPGK、ADPRH、ADPRHL1、ADPRHL2、ADPRM、ADRA1A、ADRA1B、ADRA1D、ADRA2A、ADRA2B、ADRA2C、ADRB1、ADRB2、ADRB3、ADRM1、ADSL、ADSS、ADSSL1、ADTRP、AEBP1、AEBP2、AEN、AES、AF130351.1、AF241726.2、 AFAP1, AFAP1L1, AFAP1L2, AFDN, AFF1, AFF2, AFF3, AFF4, AFG1L, AFG3L2, AFM, AFMID, AFP, AFTPH, AGA, AGAP1, AGAP2, AGAP3, AGAP4, AGAP5, AGAP6, AGAP9, AGBL1, AGBL2, AGBL3, AGBL4, AGBL5, AGER, AGFG1, AGFG2, AGGF1, AGK, AGL, AGMAT, AGMO, AGO1 、AGO2、AGO3、AGO4、AGPAT1、AGPAT2、AGPAT3、AGPAT4、AGPAT5、AGPS、AGR2、AGR3、AG RN、AGRP、AGT、AGTPBP1、AGTR1、AGTR2、AGTRAP、AGXT、AGXT2、AHCTF1、AHCY、AHCYL1 、AHCYL2、AHDC1、AHI1、AHNAK、AHNAK2、AHR、AHRR、AHSA1、AHSA2、AHSG、AHSP、AICD A、AIDA、AIF1、AIF1L、AIFM1、AIFM2、AIFM3、AIG1、AIM2、AIMP1、AIMP2、AIP、AIPL1、 AIRE、 AJAP1、AJUBA、AK1、AK2、AK3、AK4、AK5、AK6、AK7、AK8、AK9、AKAIN1、AKAP1、A KAP10、AKAP11、AKAP12、AKAP13、AKAP14、AKAP17A、AKAP2、AKAP3、AKAP4、AK AP5、AKAP6、AKAP7、AKAP8、AKAP8L、AKAP9、AKIP1、AKIRIN1、AKIRIN2、AKNA、 AKNAD1、AKR1A1、AKR1B1、AKR1B10、AKR1B15、AKR1C1、AKR1C2、AKR1C3、AKR1 C4、AKR1D1、AKR1E2、AKR7A2、AKR7A3、AKR7L、AKT1、AKT1S1、AKT2、AKT3、AKT IP、AL020996.2、AL021154.3、AL021546.1、AL021997.3、AL022238.4、AL02 2318.4, AL024498.2, AL031708.1, AL032819.3, AL033529.1, AL035425.2, AL035460.1, AL049634.2, AL049650.1, AL049697.1, AL049779.1, AL04983 9.2、AL049844.1、AL049844.3、AL080251.1、AL096814.1、AL096870.1、AL1 09810.2、AL109811.4、AL109827.1、AL109936.3、AL109936.4、AL110118.2 、AL110118.4、AL117258.1、AL117339.5、AL117348.2、AL121581.1、AL1215 94.3、AL121722.1、AL121753.1、AL121758.1、AL121845.2、AL121845.3、AL 132671.2, AL132780.3, AL133352.1, AL133414.1, AL133414.2, AL136295.1, AL136295.3, AL136295.4, AL136295.5, AL136373.1, AL136531.2, AL138 694.1, AL138752.2, AL138826.1, AL139011.2, AL139260.3, AL139300.1, AL139353.1, AL157392.5, AL159163.1, AL160275.1, AL160276.1, AL160396.2、AL161669.4、AL161911.1、AL162231.1、AL162231.3、AL163195.3 、AL163636.2、AL353572.3、AL353588.1、AL354761.2、AL354822.1、A L355102.2, AL355315.1, AL355860.1, AL355916.3, AL355987.1, AL355987.3, AL356585.9, AL357673.1, AL358075.4, AL359736.1, AL359 736.3, AL359922.1, AL360181.3, AL360181.5, AL365205.1, AL365214.3, AL365232.1, AL365273.2, AL391650.1, AL449266.1, AL451007 .3, AL512428.1, AL512506.3, AL512785.2, AL513165.2, AL513523.10, AL513523.9, AL583836.1, AL589666.1, AL590132.1, AL590560.1. AL591806.3, AL592183.1, AL592490.1, AL593848.2, AL603832.3, AL645922.1, AL645941.2, AL662828.1, AL662852.6, AL662899.1, AL662899.2, AL662899.3, AL669918.1, AL672043.1, AL672142.1, AL691442.1, AL713999.1, AL772284.2, AL807752.6, AL8077 52.7, AL844853.2, AL845331.2, AL845464.1, AL928654.4, AL929554.1, AL929561.7, ALAD, ALAS1, ALAS2, ALB, ALCAM, ALDH16A1, ALDH18A1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH1L1, ALDH1L2, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH4A1, ALDH5A1 、ALDH6A1、ALDH7A1、ALDH8A1、ALDH9A1、ALDOA、ALDOB、ALDOC、ALG1、ALG10、ALG10B、 ALG11、ALG12、ALG13、ALG14、ALG1L、ALG1L2、ALG2、ALG3、ALG5、ALG6、ALG8、ALG9、AL K、ALKAL1、ALKAL2、ALKBH1、ALKBH2、ALKBH3、ALKBH4、ALKBH5、ALKBH6、ALKBH7、ALKB H8、ALLC、ALMS1、ALOX12、ALOX12B、ALOX15、ALOX15B、ALOX5、ALOX5AP、ALOXE3、ALPI 、ALPK1、ALPK2、ALPK3、ALPL、ALPP、ALPPL2、ALS2、ALS2CL、ALS2CR12、ALX1、ALX3、ALX4、ALYREF、AMACR、A MBN、AMBP、AMBRA1、AMD1、AMHDD1、AMDHD2、AMELX、AMELY、AMER1、AMER2、AMER3、AMFR、AMH、AMHR2、AMIGO1、 AMIGO2, AMIGO3, AMMECR1, AMMECR1L, AMN, AMN1, AMOT, AMOTL1, AMOTL2, AMPD1, AMPD2, AMPD3, AMPH, AMT, AMTN, AMY1A, AMY1B, AMY1C, AMY2A, AMY2B, AMZ1, AMZ2, ANAPC1, ANAPC10, ANAPC11, ANAPC13, ANAPC15, ANAP C16、ANAPC2、ANAPC4、ANAPC5、ANAPC7、ANG、ANGEL1、ANGEL2、ANGPT1、ANGPT2、ANGPT4、ANGPTL1、ANGPTL2、 ANGPTL3、ANGPTL4、ANGPTL5、ANGPTL6、ANGPTL7、ANGPTL8、ANHX、ANK1、ANK2、ANK3、ANKAR、ANKDD1A、ANKDD 1B、ANKEF1、ANKFN1、ANKFY1、ANKH、ANKHD1、ANKHD1-EIF4EBP3、ANKIB1、ANKK1、ANKLE1、ANKLE2、ANKMY1、A NKMY2、ANKRA2、ANKRD1、ANKRD10、ANKRD11、ANKRD12、ANKRD13A、ANKRD13B、ANKRD13C、ANKRD13D、ANKRD16 、ANKRD17、ANKRD18A、ANKRD18B、ANKRD2、ANKRD20A1、ANKRD20A2、ANKRD20A3、ANKRD20A4、ANKRD20A8P、ANKRD22、ANKRD23、ANKRD24、ANKRD26、ANKRD27、ANKRD28、ANKRD29、ANKRD30A、ANKRD30B、ANKRD30BL、ANKRD31、ANKRD33、ANKRD33B、ANKRD34A、ANKRD34B、ANKRD34C、ANKRD35、ANKRD36、ANKRD36B、ANKRD36C、ANKRD37、ANKRD39、ANKRD40、ANKRD42 、ANKRD44、ANKRD45、ANKRD46、ANKRD49、ANKRD50、ANKRD52、ANKRD53、ANKRD54、ANKRD55、ANKRD6、ANKRD60、ANKRD61、ANKRD62、ANKRD63、ANKRD65、ANKRD66、ANKRD7、ANKRD9 、ANKS1A、ANKS1B、ANKS3、ANKS4B、ANKS6、ANKUB1、ANKZF1、ANLN、ANO1、ANO10、ANO2 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、C12orf54、C12orf56、C12orf57、C12orf60、C12orf65、C12orf66、C12orf71、C12orf73、C12orf74、C12orf75、C12orf76、C13orf42、C14orf105、C14orf119、C14orf132、C14orf159、C14orf166、C14orf177、C14orf178、C14orf180、C14orf2、C14orf28、C14orf37、C14orf39、C14orf79、C14orf80、C14orf93、C15orf38-AP3S2、C15orf39、C15orf40、C15orf41、C15orf48、C15orf52、C15orf53、C15orf59、C15orf61、C15orf62、C15orf65、C16orf45、C16orf46、C16orf52、C16orf54、C16orf58、C16orf59、C16orf62、C16orf70、C16orf71、C16orf72、C16orf74、C16orf78、C16orf82、C16orf86、C16orf87、C16orf89、C16orf90、C16orf91、C16orf92、C16orf95、C16orf96、C17orf100、C17orf105、C17orf107、C17orf113、C17orf47、C17orf49、C17orf50、C17orf51、C17orf53、C17orf58、C17orf62、C17orf64、C17orf67、C17orf74、C17orf75、C17orf78、C17orf80、C17orf97、C17orf98、C17orf99、C18orf21、C18orf25、C18orf32、C18orf54、C18orf63、C18orf8、C19orf12、C19orf18、C19orf24、C19orf25、C19orf33、C19orf35、C19orf38、C19orf44、C19orf47、C19orf48、C19orf53、C19orf54、C19orf57、C19orf60、C19orf66、C19orf67、C19orf68、C19orf70、C19orf71、C19orf73、C19orf81、C19orf84、C1D、C1GALT1、C1GALT1C1、C1GALT1C1L、C1orf100、C1orf105、C1orf109、C1orf112、C1orf115、C1orf116、C1orf122、C1orf123、C1orf127、C1orf131、C1orf141、C1orf146、C1orf158、C1orf159、C1orf162、C1orf167、C1orf174、C1orf185、C1orf186、C1orf189、C1orf194、C1orf198、C1orf21、C1orf210、C1orf216、C1orf226、C1orf228、C1orf232、C1orf27、C1orf35、C1orf43、C1orf50、C1orf52、C1orf53、C1orf54、C1orf56、C1orf61、C1orf64、C1orf68、C1orf74、C1orf87、 、C1orf94、C1QA、C1QB、C1QBP、C1QC、C1QL1、C1QL2、C1QL3、C1QL4、C1QTNF1、C1QTNF12、C1QTNF2、C1QTNF3、C1QTNF3-AMACR、C1QTNF4、C1QTNF5、C1QTNF6、C1QTNF7、C1QTNF8 、C1QTNF9、C1QTNF9B、C1R、C1RL、C1S、C2、C20orf141、C20orf144、C20orf173、C20orf194、C20orf196、C20orf202、C20orf204、C20orf24、C20orf27、C20orf85、C20orf96、C21orf140、C21orf2、C21orf33、C21orf58、C21orf59、C21orf62、C21orf91、C22orf15、C22orf23、C22orf31、C22orf39、C22orf42、C22orf46、C2CD2、C2CD2L、C2CD3、C2CD4A、C2CD4B、C2CD4C、C2CD4D、C2CD5、C2CD6、C2orf15、C2orf16、C2orf40、C2orf42、C2orf49 ,C2orf50,C2orf54,C2orf66,C2orf68,C2orf69,C2orf70,C2orf71,C2orf72,C2orf73,C2orf74,C2orf76,C2orf78,C2orf80,C2orf81,C2orf82,C2orf83,C2orf88,C2orf91,C3,C3AR1,C3orf14,C3orf18,C3orf20,C3orf22,C3orf30,C3orf33,C3orf35,C3orf36,C3orf38,C3orf49,C3orf52,C3orf56 、C3orf58、C3orf62、C3orf67、C3orf70、C3orf80、C3orf84、C3orf85、C4A、C4B、C4B_2、C4BPA、C4BPB、C4orf17、C4orf19、C4orf22、C4orf26、C4orf3、C4 orf32、C4orf33、C4orf36、C4orf45、C4orf46、C4orf47、C4orf48、C4orf50、C4orf51、C5、C5AR1、C5AR2、C5orf15、C5orf22、C5orf24、C5orf30、C5orf34、 C5orf38, C5orf42, C5orf46, C5orf47, C5orf49, C5orf51, C5orf52, C5orf56, C5orf58, C5orf60, C5orf63, C5orf67, C6, C6orf10, C6orf106, C6orf118, C6orf120, C6orf132, C6orf136, C6orf141, C6orf15, C6orf163, C6orf201, C6orf203, C6orf222, C6orf223, C6orf226, C6orf229, C6orf47, C6orf48, C 6orf52、C6orf58、C6orf62、C6orf89、C7、C7、C7orf25、C7orf26、C7orf31、C7orf33、C7orf34、C7orf43、C7orf49、C7orf50、C7orf55-LUC7L2、C7orf57、C7orf61、C7orf72、C7orf73、C7orf77、C8A、C8B、C8G、C8orf22、C8orf33、C8orf34、C8orf37、C8orf4、C8orf44、C8orf44-SGK3、C8orf46、C8orf48、C8orf58、C8orf59、C8orf74、C8orf76、C8orf82、C8orf86、C8orf88、C8orf89、C9、C9orf116、C9orf129、C9orf131、C9orf135、C9orf152、C9orf153、C9orf16、C9orf172、C9orf24、C9orf3、C9orf40、C9orf43、C9orf47、C9orf50、C9orf57、C9orf64、C9orf66、C9orf72、C9orf78、C9orf84、C9orf85、C9orf92、CA1、CA10、CA11、CA12、CA13、CA14、CA2、CA3、 、CA4、CA5A、CA5B、CA6、CA7、CA8、CA9、CAAP1、CAB39、CAB39L、CABIN1、CABLES1、CABLES2、CABP1、CABP2、CABP4、CABP5、CABP7、CABS1、CABYR、CACFD1、CACHD1、CACNA1A 、CACNA1B、CACNA1C、CACNA1D、CACNA1E、CACNA1F、CACNA1G、CACNA1H、CACNA1I、CACNA1S、CACNA2D1、CACNA2D2、CACNA2D3、CACNA2D4、CACNB1、CACNB2、CACNB3、CACNB4、CACNG 1、CACNG2、CACNG3、CACNG4、CACNG5、CACNG6、CACNG7、CACNG8、CACTIN、CACUL1、CACY BP、CAD、CADM1、CADM2、CADM3、CADM4、CADPS、CADPS2、CAGE1、CALB1、CALB2、CALCA、C ALCB、CALCOCO1、CALCOCO2、CALCR、CALCRL、CALD1、CALHM1、CALHM2、CALHM3、CALM1、 CALM2、CALM3、CALML3、CALML4、CALML5、CALML6、CALN1、CALR、CALR3、CALU、CALY、CAM K1、CAMK1D、CAMK1G、CAMK2A、CAMK2B、CAMK2D、CAMK2G、CAMK2N1、CAMK2N2、CAMK4、CA MKK1, CAMKK2, CAMKMT, CAMKV, CAMLG, CAMP, CAMSAP1, CAMSAP2, CAMSAP3, CAMTA1, CA MTA2、CAND1、CAND2、CANT1、CANX、CAP1、CAP2、CAPG、CAPN1、CAPN10、CAPN11、CAPN12 、CAPN13、CAPN14、CAPN15、CAPN2、CAPN3、CAPN5、CAPN6、CAPN7、CAPN8、CAPN9、CAPNS1 、CAPNS2、CAPRIN1、CAPRIN2、CAPS、CAPS2、CAPSL、CAPZA1、CAPZA2、CAPZA3、CAPZB、CARD10、CARD11、CARD14、CARD16、CARD17、CARD18、CARD19、CARD6、CARD8、CARD9、CARF、CARHSP1、CARM1、CARMIL1、CARMIL2、CARMIL3、CARNMT1、CARNS1、CARS、CARS2、CARTPT、CASC1、CASC10、CASC3、CASC4、CASD1、CASK、CASKIN1、CASKIN2、CASP1、CASP10、CASP12、CASP14、CASP2、CASP3、CASP4、CASP5、CASP6、CASP7、CASP8、CASP8AP2、CASP9、CASQ1、CASQ2、CASR、CASS4、CAST、CASTOR1、CASTOR2、CASZ1、CAT、CATIP、CATSPER1、CATSPER2、CATSPER3、CATSPER4、CATSPERB、CATSPERD、CATSPERE、CATSPERG、CATSPERZ、CAV1、CAV2、CAV3、CAVIN1、CAVIN2、CAVIN3、CAVIN4、CBARP、CBFA2T2、CBFA2T3、CBFB 、CBL、CBLB、CBLC、CBLL1、CBLN1、CBLN2、CBLN3、CBLN4、CBR1、CBR3、CBR4、CBS、CBSL、CBWD1、CBWD2、CBWD3、CBWD5、CBWD6、CBX1、CBX2、CBX3、CBX4、CBX5、CBX6、CBX7、CBX8、CBY1、CBY3、CC2D1A、CC2D1B、CC2D2A、CC2D2B、CCAR1、CCAR2、CCBE1、CCDC102A 、CCDC102B、CCDC103、CCDC105、CCDC106、CCDC107、CCDC110、CCDC112、CCDC113、CCDC114、CCDC115、CCDC116、CCDC117、CCDC12、CCDC120、CCDC121、CCDC122、CCDC124、CCDC125、CCDC126、CCDC127、CCDC129、CCDC13、CCDC130、CCDC134、CCDC136、CCDC137、CCDC138、CCDC14、CCDC140、CCDC141、CCDC142、CCDC144A、CCDC144NL、CCDC146、CCDC148、CCDC149、CCDC15、CCDC150、CCDC151、CCDC152、CCDC153、CCDC154、CCDC155、CCDC157、CCDC158、CCDC159、CCDC160、CCDC163、CCDC166、CCDC167、CCDC168、CCDC169、CCDC169-SOHLH2、CCDC17、CCDC170、CCDC171、CCDC172、CCDC173、CCDC174、CCDC175、CCDC177、CCDC178、CCDC179、CCDC18、CCDC180、CCDC181、CCDC182、CCDC183、CCDC184、CCDC185、CCDC186、CCDC187、CCDC188、CCDC189、CCDC190、CCDC191、CCDC192、CCDC194、CCDC195、CCDC196、CCDC197、CCDC22、CCDC24、CCDC25、CCDC27、CCDC28A、CCDC28B、CCDC3、CCDC30 、CCDC32、CCDC33、CCDC34、CCDC36、CCDC38、CCDC39、CCDC40、CCDC42、CCDC43、CCDC47、CCDC50、CCDC51、CCDC54、CCDC57、CCDC58、CCDC59、CCDC6、CCDC60、CCDC61、CCDC62 、CCDC63、CCDC65、CCDC66、CCDC68、CCDC69、CCDC7、CCDC70、CCDC71、CCDC71L、CCDC73、CCDC74A、CCDC74B、CCDC77、CCDC78、CCDC 8、CCDC80、CCDC81、CCDC82、CCDC83、CCDC84、CCDC85A、CCDC85B、CCDC85C、CCDC86、CCDC87、CCDC88A、CCDC88B、CCDC88C、CCDC89 ,CCDC9,CCDC90B,CCDC91,CCDC92,CCDC93,CCDC94,CCDC96,CCDC97,CCER1,CCER2,CCHCR1,CCIN,CCK,CCKAR,CCKBR,CCL1,CCL11,CCL13,CCL14,CCL15,CCL15-CCL14,CCL16,CCL17,CCL18,CCL19,CCL2,CCL20,CCL21,CCL22,CCL23,CCL24,CCL25,CCL26,CCL27,CCL28,CCL3,CCL3L1,CCL3L3,CCL4,CCL4L2,CCL5,CCL7,CCL8,CCM2,CCM2L,CCNA1,CCNA2,CCNB1,CCNB1IP1,CC NB2、CCNB3、CCNC、CCND1、CCND2、CCND3、CCNDBP1、CCNE1、CCNE2、CCNF、CCNG1、CCNG2、CCNH、CCNI、CCNI2、CCNJ、CCNJL、CCNK、CCNL1、CCNL2、CCNO、CCNT1、CCNT2、CCNY、CCNYL1、CCP110、CCPG 1. 、CD14、CD151、CD160、CD163、CD163L1、CD164、CD164L2、CD177、CD180、CD19、CD1A、CD1B、CD1C、CD1D、CD1E、CD2、CD200、CD200R1、CD200R1L、CD2 07、CD209、CD22、CD226、CD24、CD244、CD247、CD248、CD27、CD274、CD276、CD28、CD2AP、CD2BP2、CD300A、CD300C、CD300E、CD300LB、CD300LD、CD30LD 0LF、CD300LG、CD302、CD320、CD33、CD34、CD36、CD37、CD38、CD3D、CD3E、CD3EAP、CD3G、CD4、CD40、CD40LG、CD44、CD46、CD47、CD48、CD5、CD52、CD5 3、CD55、CD58、CD59、CD5L、CD6、CD63、CD68、CD69、CD7、CD70、CD72、CD74、CD79A、CD79B、CD80、CD81、CD82、CD83、CD84、CD86、CD8A、CD8B、CD9、CD9 3、CD96、CD99、CD99L2、CDA、CDADC1、CDAN1、CDC123、CDC14A、CDC14B、CDC16、CDC20 、CDC20B、CDC23、CDC25A、CDC25B、CDC25C、CDC26、CDC27、CDC34、CDC37、CDC37L1、CDC40、CDC42、CDC42BPA、CDC42BPB、CDC42BPG、CDC42EP1、CDC42 EP2、CDC42EP3、CDC42EP4、CDC42EP5、CDC42SE1、CDC42SE2、CDC45、CDC5L、CDC6、CDC7、CDC73、CDCA2、CDCA3、CDCA4、CDCA5、CDCA7、CDCA7L、CDCA8、C DCP1、CDCP2、CDH1、CDH10、CDH11、CDH12、CDH13、CDH15、CDH16、CDH17、CDH18、CDH19、CDH2、CDH20、CDH22、CDH23、CDH24、CDH26、CDH3、CDH4、CDH5、CDH1 DH6、CDH7、CDH8、CDH9、CDHR1、CDHR2、CDHR3、CDHR4、CDHR5、CDIP1、CDIPT、CDK1、CDK10、CDK11A、CDK11B、CDK12、CDK13、CDK14、CDK15、CDK16、CDK17 、CDK18、CDK19、CDK2 、CDK20、CDK2AP1、CDK2AP2、CDK3、CDK4、CDK5、CDK5R1、CDK5R2、CDK5RAP1、CDK5RAP2 ,CDK5RAP3,CDK6,CDK7,CDK8,CDK9,CDKAL1,CDKL1,CDKL2,CDKL3,CDKL4,CDKL5,CDKN1A,CDKN1B,CDKN1C,CDKN2A,CDKN2AIP,CDKN2AIPNL,CDKN2B,CDKN2C,CDKN2D,CDKN3,CDNF,CDO1,CDON,CDPF1,CDR1,CDR2,CDR2L,CDRT1,CDRT15,CDRT15L2,CDRT4,CDS1,CDS2,CDSN,CDT1,CDV3,CDX1,CDX2,CDX4,CDY1,CDY1B,CDY2A,CDY2B,CDYL 、CDYL2、CEACAM1、CEACAM16、CEACAM19、CEACAM20、CEACAM21、CEACAM3、CEACAM4、CEACAM5、CEACAM6、CEA CAM7、CEACAM8、CEBPA、CEBPB、CEBPD、CEBPE、CEBPG、CEBPZ、CEBPZOS、CECR2、CEL、CELA1、CELA2A、CELA2B、 CELA3A、CELA3B、CELF1、CELF2、CELF3、CELF4、CELF5、CELF6、CELSR1、CELSR2、CELSR3、CEMIP、CEMP1、CEND 1、CENPA、CENPB、CENPBD1、CENPC、CENPE、CENPF、CENPH、CENPI、CENPJ、CENPK、CENPL、CENPM、CENPN、CENPO 、CENPP、CENPQ、CENPS、CENPS-CORT、CENPT、CENPU、CENPV、CENPVL1、CENPVL2、CENPV L3、CENPW、CENPX、CEP104、CEP112、CEP120、CEP126、CEP128、CEP131、CEP135、CEP152 CEP162, CEP164, CEP170, CEP170B, CEP19, CEP192, CEP250, CEP290, CEP295, CEP295NL, CEP350, CEP41, CEP44, CEP55, CEP57, CEP57L1, CEP63, CEP68, CEP70, CEP72, CEP76, CEP78, CEP83, CEP85, CEP85L, CEP89, CEP95, CEP97, CEPT1, CER1, CERCAM, CERK 、CERKL、CERS1、CERS2、CERS3、CERS4、CERS5、CERS6、CES1、CES2、CES3、CES4A、CES5A、CETN1、CETN2、CETN3、CETP、CFAP100、CFAP126、CFAP157、CFAP161、CFAP20、CFAP206、CFAP221、CFAP36、CFAP43、CFAP44、CFAP45、CFAP46、CFAP47、CFAP52、CFAP53、CFAP54、CFAP57、CFAP58、CFAP61、CFAP65、CFAP69、CFAP70、CFAP73、CFAP74、CFAP77、CFAP97、CFAP99、CFB、CFC1、CFC1B、CFD、CFDP1、CFH、CFHR1、CFHR2、CFHR3、CFHR4、CFHR5、CFI、CFL1、CFL2、CFLAR、CFP、CFTR、CGA、CGB1、CGB2、CGB3、CGB5、CGB7、CGB8、CGGBP1、CGN、CGNL1、CGREF1、CGRRF1、CH25H、CHAC1、CHAC2、CHAD、CHADL、CHAF1A、CHAF1B、CHAMP1、CHAT、CHCHD1、CHCHD10、CHCHD2、CHCHD3、CHCHD4、CHCHD5、CHCHD6、CHCHD7、CHD1、CHD1L、CHD2、CHD3、CHD4、CHD5、CHD6、CHD7、CHD8、CHD9、CHDH、CHEK1、CHEK2、CHERP、CHFR、CHGA、CHGB、CHI3L1、CHI3L2、CHIA、CHIC1、CHIC2、CHID1、CHIT1、CHKA、CHKB、CHKB-CPT1B、CHL1、CHM、CHML、CHMP1A、CHMP1B、CHMP2A、CHMP2B、CHMP3、CHMP4A、CHMP4B、CHMP4C、CHMP5、CHMP6、CHMP7、CHN1、CHN2、CHODL、CHORDC1、CHP1、CHP2、CHPF、CHPF2、CHPT1、CHRAC1、CHRD、CHRDL1、CHRDL2、CHRFAM7A、CHRM1、CHRM2、CHRM3、CHRM4、CHRM5、CHRNA1、CHRNA10、CHRNA2、CHRNA3、CHRNA4、CHRNA5、CHRNA6、CHRNA7、CHRNA9、CHRNB1、CHRNB2、CHRNB3、CHRNB4、CHRND、CHRNE、CHRNG、CHST1、CHST10、CHST11、CHST12、CHST13、CHST14、CHST15、CHST2、CHST3、CHST4、CHST5、CHST6、CHST7、CHST8、CHST9、CHSY1、CHSY3、CH TF18、CHTF8、CHTOP、CHUK、CHURC1、CHURC1-FNTB、CIAO1、CIAPIN1、CIART、CIB1、CIB2、CIB3、CIB4、CIC、CIDEA、CIDEB、CIDEC、CIITA、CILP、CILP2、CINP、CIP C、CIR1、CIRBP、CISD1、CISD2、CISD3、CISH、CIT、CITED1、CITED2、CITED4、CIZ1、CKAP2、CKAP2L、CKAP4、CKAP5、CKB、CKLF、CKLF-CMTM1、CKM、CKMT1A、CKMT1B 、CKMT2、CKS1B、CKS2、CLASP1、CLASP2、CLASRP、CLC、CLCA1、CLCA2、CLCA4、CLCC1、CLCF1、CLCN1、CLCN2、CLCN3、CLCN4、CLCN5、CLCN6、CLCN7、CLCNKA、CLCNKB、 、CLDN1、CLDN10、CLDN11、CLDN12、CLDN14、CLDN15、CLDN16、CLDN17、CLDN18、CLDN19 、CLDN2、CLDN20、CLDN22、CLDN23、CLDN24、CLDN25、CLDN3、CLDN34、CLDN4、CLDN5、CLDN6、CLDN7、CLDN8、CLDN9、CLDND1、CLDND2、 CLEC10A、CLEC11A、CLEC12A、CLEC12B、CLEC14A、CLEC16A、CLEC17A、CLEC18A、CLEC18B、CLEC18C、CLEC19A、CLEC1A、CLEC1B、CLE C20A、CLEC2A、CLEC2B、CLEC2D、CLEC2L、CLEC3A、CLEC3B、CLEC4A、CLEC4C、CLEC4D、CLEC4E、CLEC4F、CLEC4G、CLEC4M、CLEC5A、CLEC6A、CLEC7A、CLEC9A、CLECL1、CLGN、CLHC1、CLIC1、CLIC2、CLIC3、CLIC4、CLIC5、CLIC6、CLINT1、CLIP1、CLIP2、CLIP3、CLIP4 , CLK1, CLK2, CLK3, CLK4, CLLU1, CLLU1OS, CLMN, CLMP, CLN3, CLN5, CLN6, CLN8, CLNK, CLNS1A, CLOCK, CLP1, CLPB, CLPP, CLPS, CLPSL1, CLPSL2, CL PTM1, CLPTM1L, CLPX, CLRN1, CLRN2, CLRN3, CLSPN, CLSTN1, CLSTN2, CLSTN3, CLTA, CLTB, CLTC, CLTCL1, CLU, CLUAP1, CLUH, CLUL1, CLVS1, CLVS2, C LYBL、CMA1、CMAS、CMBL、CMC1、CMC2、CMC4、CMIP、CMKLR1、CMPK1、CMPK2、CMSS1、CMTM1、CMTM2、CMTM3、CMTM4、CMTM5、CMTM6、CMTM7、CMTM8、CMTR1、C MTR2, CMYA5, CNBD1, CNBD2, CNBP, CNDP1, CNDP2, CNEP1R1, CNFN, CNGA1, CNGA2, CNGA3, CNGA4, CNGB1, CNGB3, CNIH1, CNIH2, CNIH3, CNIH4, CNKSR1, CNKSR2, CNKSR3, CNMD, CNN1, CNN2, CNN3, CNNM1, CNNM2, CNNM3, CNNM4, CNOT1, CNOT10, CNOT11, CNOT2, CNOT3, CNOT4, CNOT6, CNOT6L, CNOT7, CNOT8 , CNOT9, CNP, CNPPD1, CNPY1, CNPY2, CNPY3, CNPY4, CNR1, CNR2, CNRIP1, CNST, CNTD1, CNTD2, CNTF, CNTFR, CNTLN, CNTN1, CNTN2, CNTN3, CNTN4, CNT N5、CNTN6、CNTNAP1、CNTNAP2、CNTNAP3、CNTNAP3B、CNTNAP4、CNTNAP5、CNTRL、CNTROB、COA1、COA3、COA4、COA5、COA6、COA7、COASY、COBL、COBLL1、C OCH、COG1、COG2、COG3、COG4、COG5、COG6、COG7、COG8、COIL、COL10A1、COL11A1、COL11A2、COL12A1、COL13A1、COL14A1、COL15A1、COL16A1、COL17A1 、COL18A1、COL19A1、COL1A1、COL1A2、COL20A1、COL21A1、COL22A1、COL23A1、COL24A1 、COL25A1、COL26A1、COL27A1、COL28A1、COL2A1、COL3A1、COL4A1、COL4A2、COL4A3、COL4A3BP、COL4A4、COL4A5、COL4A6、COL5A1、COL5A2、COL5A3、COL6A1、COL6A2、COL6A3、COL6A5、COL6A6、COL7A1、COL8A1、COL8A2、COL9A1、COL9A2、COL9A3、COLCA2、COLEC10 、COLEC11、COLEC12、COLGALT1、COLGALT2、COLQ、COMMD1、COMMD10、COMMD2、COMMD3、COMMD3-BMI1、COMMD4、COMMD5、COMMD6、COMMD7、COMMD8、COMMD9、COMP、COMT、COMTD1、COPA、COPB1、COPB2、COPE、COPG1、COPG2、COPRS、COPS2、COP S3、COPS4、COPS5、COPS6、COPS7A、COPS7B、COPS8、COPS9、COPZ1、COPZ2、COQ10A、COQ10B、COQ2、COQ3、COQ4、COQ5、C OQ6、COQ7、COQ8A、COQ8B、COQ9、CORIN、CORO1A、CORO1B、CORO1C、CORO2A、CORO2B、CORO6、CORO7、CORO7-PAM16、CORT [COTL1] COX10 [COX11] COX14 COX6A2、COX6B1、COX6B2、COX6C、COX7A1、COX7A2、COX7A2L、COX7B、COX7B2、COX7C、COX8A、COX8C、CP、CPA1、CPA2、CP A3、CPA4、CPA5、CPA6、CPAMD8、CPB1、CPB2、CPD、CPE、CPEB1、CPEB2、CPEB3、CPEB4、CPED1、CPLX1、CPLX2、CPLX3、CPL x4 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F1A2, EEF1AKMT1, EEF1AKMT2, EEF1AKMT3, EEF1B2, EEF1D, EEF1E1, EEF1E1-BLOC1S5 EEF1G、EEF2、EEF2K、EEF2KMT、EEFSEC、EEPD1、EFCAB1、EFCAB10、EFCAB11、EFCAB12、E FCAB13, EFCAB14, EFCAB2, EFCAB3, EFCAB5, EFCAB6, EFCAB7, EFCAB8, EFCAB9, EFCC1 EFEMP1、EFEMP2、EFHB、EFHC1、EFHC2、EFHD1、EFHD2、EFL1、EFNA1、EFNA2、EFNA3、EFNA4、EFNA5、EFNB1、EFNB2、EFNB3、EFR3A、E FR3B、EFS、EFTUD2、EGF、EGFL6、EGFL7、EGFL8、EGFLAM、EGFR、EGLN1、EGLN2、EGLN3、EGR1、EGR2、EGR3、EGR4、EHBP1、EHBP1L1、E HD1、EHD2、EHD3、EHD4、EHF、EHHADH、EHMT1、EHMT2、EI24、EID1、EID2、EID2B、EID3、EIF1、EIF1AD、EIF1AX、EIF1AY、EIF1B、EIF 2A、EIF2AK1、EIF2AK2、EIF2AK3、EIF2AK4、EIF2B1、EIF2B2、EIF2B3、EIF2B4、EIF2B5、EIF2D、EIF2S1、EIF2S2、EIF2S3、EIF3A、E IF3B、EIF3C、EIF3CL、EIF3D、EIF3E、EIF3F、EIF3G、EIF3H、EIF3I、EIF3J、EIF3K、EIF3L、EIF3M、EIF4A1、EIF4A2、EIF4A3、EIF4 B、EIF4E、EIF4E1B、EIF4E2、EIF4E3、EIF4EBP1、EIF4EBP2、EIF4EBP3、EIF4ENIF1、EIF4G1、EIF4G2、EIF4G3、EIF4H、EIF5、EIF5 A、EIF5A2、EIF5AL1、EIF5B、EIF6、EIPR1、ELAC1、ELAC2、ELANE、ELAVL1、ELAVL2、ELAVL3、ELAVL4、ELF1、ELF2、ELF3、ELF4、ELF 5、ELFN1、ELFN2、ELK1、ELK3、ELK4、ELL、ELL2、ELL3、ELMO1、ELMO2、ELMO3、ELMOD1、ELMOD2、ELMOD3、ELMSAN1、ELN、ELOA、ELOA2 、ELOA3、ELOA3B、ELOA3C、ELOA3D、ELOB、ELOC、ELOF1、ELOVL1、ELOVL2、ELOV L3、ELOVL4、ELOVL5、ELOVL6、ELOVL7、ELP1、ELP2、ELP3、ELP4、ELP5、ELP6、E LSPBP1、EMB、EMC1、EMC10、EMC2、EMC3、EMC4、EMC6、EMC7、EMC8、EMC9、EMCN、 EMD、EME1、EME2、EMG1、EMID1、EMILIN1、EMILIN2、EMILIN3、EML1、EML2、EML3 、EML4、EML5、EML6、EMP1、EMP2、EMP3、EMSY、EMX1、EMX2、EN1、EN2、ENAH、ENA M、ENC1、ENDOD1、ENDOG、ENDOU、ENDOV、ENG、ENGASE、ENHO、ENKD1、ENKUR、EN O1、ENO2、ENO3、ENO4、ENOPH1、ENOSF1、ENOX1、ENOX2、ENPEP、ENPP1、ENPP2、 ENPP3、ENPP4、ENPP5、ENPP6、ENPP7、ENSA、ENTHD1、ENTPD1、ENTPD2、ENTPD3、 ENTPD4、ENTPD5、ENTPD6、ENTPD7、ENTPD8、ENY2、EOGT、EOMES、EP300、EP400 、EPAS1、EPB41、EPB41L1、EPB41L2、EPB41L3、EPB41L4A、EPB41L4B、EPB41L5 、EPB42、EPC1、EPC2、EPCAM、EPDR1、EPG5、EPGN、EPHA1、EPHA10、EPHA2、EPHA 3、EPHA4、EPHA5、EPHA6、EPHA7、EPHA8、EPHB1、EPHB2、EPHB3、EPHB4、EPHB6、E PHX1、EPHX2、EPHX3、EPHX4、EPM2A、EPM2AIP1、EPN1、EPN2、EPN3、EPO、EPOP、 EPOR, EPPIN, EPPIN-WFDC6, EPPK1, EPRS, EPS15, EPS15L1, EPS8, EPS8L1, EPS 8L2、EPS8L3、EPSTI1、EPX、EPYC、EQTN、ERAL1、ERAP1、ERAP2、ERAS、ERBB2、E RBB3、ERBB4、ERBIN、ERC1、ERC2、ERCC1、ERCC2、ERCC3、ERCC4、ERCC5、ERCC6、ERCC6L、ERCC6L2、ERCC8、EREG、ERF、 ERFE, ERG, ERG28, ERGIC1, ERGIC2, ERGIC3, ERH, ERI1, ERI2, ERI3, ERICH1, ERICH2, ERICH3, ERICH4, E RICH5、ERICH6、ERICH6B、ERLEC1、ERLIN1、ERLIN2、ERMAP、ERMARD、ERMN、ERMP1、ERN1、ERN2、ERO1A、ERO1 B, ERP27, ERP29, ERP44, ERRFI1, ERV3-1, ERVFRD-1, ERVMER34-1, ERVV-1, ERVV-2, ERVW-1, ESAM, ESCO1, ESCO2、ESD、ESF1、ESM1、ESPL1、ESPN、ESPNL、ESR1、ESR2、ESRP1、ESRP2、ESRRA、ESRRB、ESRRG、ESS2、ESX1 、ESYT1、ESYT2、ESYT3、ETAA1、ETDA、ETDB、ETDC、ETF1、ETFA、ETFB、ETFBKMT、ETFD H、ETFRF1、ETHE1、ETNK1、ETNK2、ETNPPL、ETS1、ETS2、ETV1、ETV2、ETV3、ETV3L、ETV 4、ETV5、ETV6、ETV7、EVA1A、EVA1B、EVA1C、EVC、EVC2、EVI2A、EVI2B、EVI5、EVI5L、 EVL、EVPL、EVPLL、EVX1、EVX2、EWSR1、EXD1、EXD2、EXD3、EXO1、EXO5、EXOC1、EXOC1L 、EXOC2、EXOC3、EXOC3L1、EXOC3L2、EXOC3L4、EXOC4、EXOC5、EXOC6、EXOC6 B、EXOC7、EXOC8、EXOG、EXOSC1、EXOSC10、EXOSC2、EXOSC3、EXOSC4、EXOSC5 、EXOSC6、EXOSC7、EXOSC8、EXOSC9、EXPH5、EXT1、EXT2、EXTL1、EXTL2、EXTL 3、EYA1、EYA2、EYA3、EYA4、EYS、EZH1、EZH2、EZR、F10、F11、F11R、F12、F13A 1, F13B, F2, F2R, F2RL1, F2RL2, F2RL3, F3, F5, F7, F8, F8A1, F8A2, F8A3, F9, FA2H, FAAH, FAAH2, FAAP100, FAAP20, FAAP24, FABP1, FABP12, FABP2, FAB P3, FABP4, FABP5, FABP6, FABP7, FABP9, FADD, FADS1, FADS2, FADS3, FADS6, FAF1, FAF2, FAH, FAHD1, FAHD2A, FAHD2B, FAIM, FAIM2, FAM102A, FAM102B 、FAM103A1、FAM104A、FAM104B、FAM105A、FAM106A、FAM107A、FAM107B、FA M109A、FAM109B、FAM110A、FAM110B、FAM110C、FAM110D、FAM111A、FAM111B 、FAM114A1、FAM114A2、FAM117A、FAM117B、FAM118A、FAM118B、FAM120A、FA M120AOS、FAM120B、FAM120C、FAM122A、FAM122B、FAM122C、FAM124A、FAM12 4B、FAM126A、FAM126B、FAM129A、FAM129B、FAM129C、FAM131A、FAM131B、FA M131C、FAM133A、FAM133B、FAM135A、FAM135B、FAM136A、FAM13A、FAM13B、F AM13C、FAM149A、FAM149B1、FAM151A、FAM151B、FAM153A、FAM153B、FAM153 C、FAM155A、FAM155B、FAM156A、FAM156B、FAM159A、FAM159B、FAM160A1、FA M160A2、FAM160B1、FAM160B2、FAM161A、FAM161B、FAM162A、FAM162B、FAM163A、FAM163B、FAM166A、FAM166B、FAM167A、FAM167B、FAM168A、FAM168B、FAM169A、FAM169B、FAM170A、FAM170B、FAM171A1、FAM171A2、FAM171B、FAM172A、FAM173A、FAM173B、FAM174A、FAM174B、FAM177A1、FAM177B、FAM178B、FAM180A、FAM180B、FAM181A、FAM181B、FAM182B、FAM183A、FAM184A、FAM184B、FAM185A、FAM186A、FAM186B、FAM187A、FAM187B、FAM189A1 FAM189A2, FAM189B, FAM192A, FAM193A, FAM193B, FAM196A, FAM196B, FAM198A, FAM198B, FAM199X, FAM19A1, FAM19A2, FAM19A3, FAM19A4, FAM19A5, FAM200A, FAM200B, FAM204A, FAM205A, FAM205C, FAM206A, FAM207A, FAM208A, FAM208B, FAM2 09A, FAM209B, FAM20A, FAM20B, FAM20C, FAM210A, FAM210B, FAM212A, FAM212B, FAM213A, FAM213B, FAM214A, FAM214B, FAM216A, FAM216B, FAM217A, FAM217B, FAM218A, FAM219A, FAM219B, FAM220A, FAM221A, FAM221B, FAM222A, FAM222B, FAM22 7A, FAM227B, FAM228A, FAM228B, FAM229A, FAM229B, FAM230A, FAM231A, FAM231B, FAM231C, FAM231D, FAM234A, FAM234B, FAM236A, FAM236B, FAM236C, FAM236D, FAM237A, FAM237B, FAM240A, FAM240B, FAM24A, FAM24B, FAM25A, FAM25C, FAM25G FAM26D, FAM26E, FAM26F, FAM32A, FAM35A, FAM3A, FAM3B, FAM3C, FAM3D, FAM43A, FAM43B, FAM45A, FAM46A, FAM46B, FAM46C, FAM46D, FAM47A, FAM47B, FAM47C, FAM47E, FAM47E-STBD1, FAM49A, FAM49B, FAM50A, FAM50B, FAM53A, FAM53B, FAM53C FAM57A, FAM57B, FAM58A, FAM60A, FAM69A, FAM69B, FAM69C, FAM71A, FAM71B, FAM71C, FAM71D, FAM71E1, FAM71E2, FAM71F1, FAM71F2, FAM72A, FAM72 B、FAM72C、FAM72D、FAM76A、FAM76B、FAM78A、FAM78B、FAM81A、FAM81B、FAM 83A、FAM83B、FAM83C、FAM83D、FAM83E、FAM83F、FAM83G、FAM83H、FAM84A、F AM84B、FAM86B1、FAM86B2、FAM86C1、FAM89A、FAM89B、FAM8A1、FAM90A1、F AM90A26、FAM91A1、FAM92A、FAM92B、FAM95C、FAM96A、FAM96B、FAM98A、FAM 98B、FAM98C、FAM9A、FAM9B、FAM9C、FAN1、FANCA、FANCB、FANCC、FANCD2、FA NCD2OS、FANCE、FANCF、FANCG、FANCI、FANCL、FANCM、FANK1、FAP、FAR1、FAR 2、FARP1、FARP2、FARS2、FARSA、FARSB、FAS、FASLG、FASN、FASTK、FASTKD1 、FASTKD2、FASTKD3、FASTKD5、FAT1、FAT2、FAT3、FAT4、FATE1、FAU、FAXC、F AXDC2、FBF1、FBL、FBLIM1、FBLL1、FBLN1、FBLN2、FBLN5、FBLN7、FBN1、FBN2 、FBN3、FBP1、FBP2、FBRS、FBRSL1、FBXL12、FBXL13、FBXL14、FBXL15、FBXL1 6、FBXL17、FBXL18、FBXL19、FBXL2、FBXL20、FBXL22、FBXL3、FBXL4、FBXL5 、FBXL6、FBXL7、FBXL8、FBXO10、FBXO11、FBXO15、FBXO16、FBXO17、FBXO18、 FBXO2、FBXO21、FBXO22、FBXO24、FBXO25、FBXO27、FBXO28、FBXO3、FBXO30、 FBXO31、FBXO32、FBXO33、FBXO34、FBXO36、FBXO38、FBXO39、FBXO4、FBXO40 , FBXO41, FBXO42, FBXO43, FBXO44, FBXO45, FBXO46, FBXO47, FBXO48, FBXO5, FBXO6, FBXO7, FBXO8, FBXO9, FBXW10, FBXW11, FBXW12, FBXW2, FBXW4, FBXW5, FBXW7, FBXW8, FBXW9, FCAMR, FCAR, FCER1A, FCER1G, FCER2, FCF1, FCGBP, FCGR1A, FCGR1B, FCGR2A, FCGR2B, FCGR2C, FCGR3A, FCGR3B, FCGRT, FCHO1, FCHO2, FCHSD1, FCHSD2, FCMR, FCN1 、FCN2、FCN3、FCRL1、FCRL2、FCRL3、FCRL4、FCRL5、FCRL6、FCRLA、FCRLB、FDCSP、FDFT1、FDPS、FDX1、FDX2、FDXACB1、FDXR、FE CH、FEM1A、FEM1B、FEM1C、FEN1、FER、FER1L5、FER1L6、FERD3L、FERMT1、FERMT2、FERMT3、FES、FETUB、FEV、FEZ1、FEZ2、FEZF1、 FEZF2、FFAR1、FFAR2、FFAR3、FFAR4、FGA、FGB、FGD1、FGD2、FGD3、FGD4、FGD5、FGD6、FGF1、FGF10、FGF11、FGF12、FGF13、FGF14 、FGF16、FGF17、FGF18、FGF19、FGF2、FGF20、FGF21、FGF22、FGF23、FGF3、FGF4、FGF5、FGF6、FGF7、FGF8、FGF9、FGFBP1、FGFBP2 FGFBP3, FGFR1, FGFR1OP, FGFR1OP2, FGFR2, FGFR3, FGFR4, FGFRL1, FGG, FGGY, FGL1, FGL2, F GR, FH, FHAD1, FHDC1, FHIT, FHL1, FHL2, FHL3, FHL5, FHOD1, FHOD3, FIBCD1, FIBIN, FIBP, FICD FIG4, FIGLA, FIGN, FIGNL1, FIGNL2, FILIP1, FILIP1L, FIP1L1, FIS1, FITM1, FITM2, FIZ1, FJ X1, FKBP10, FKBP11, FKBP14, FKBP15, FKBP1A, FKBP1B, FKBP1C, FKBP2, FKBP3, FKBP4, FKBP5, F KBP6, FKBP7, FKBP8, FKBP9, FKBPL, FKRP, FKTN, FLAD1, FLCN, FLG, FLG2, FLI1, FLII, FLNA, FLN B. FLNC, FLOT1, FLOT2, FLRT1, FLRT2, FLRT3, FLT1, FLT3, FLT3LG, FLT4, FLVCR1, FLVCR2, FLYW CH1, FLYWCH2, FMC1, FMN1, FMN2, FMNL1, FMNL2, FMNL3, FMO1, FMO2, FMO3, FMO4, FMO5, FMOD, FM R1, FMR1NB, FN1, FN3K, FN3KRP, FNBP1, FNBP1L, FNBP4, FNDC1, FNDC10, FNDC11, FNDC3A, FNDC3 B. FNDC4, FNDC5, FNDC7, FNDC8, FNDC9, FNIP1, FNIP2, FNTA, FN TB, FO681492.1, FO681542.1, FOCAD, FOLH1, FOLR1, FOLR2, FOL R3、FOPNL、FOS、FOSB、FOSL1、FOSL2、FOXA1、FOXA2、FOXA3、FOX B1, FOXB2, FOXC1, FOXC2, FOXD1, FOXD2, FOXD3, FOXD4, FOXD4L1 、FOXD4L3、FOXD4L4、FOXD4L5、FOXD4L6、FOXE1、FOXE3、FOXF1、FOXF2、FOXG1、FOXH1、FOXI1、FOXI2、FOXI3、FOXJ1、FOXJ2、FOXJ3、FOXK1、FOXK2、FOXL1、FOXL2、FOXL2NB、FOX XM1、FOXN1、FOXN2、FOXN3、FOXN4、FOXO1、FOXO3、FOXO4、FOXO6、FOXP1、FOXP2、FOXP3、FOXP4、FOXQ1、FOXR1、FOXR2、FOXRED1、FOXRED2、FOXS1、FP236240.1、FP565260.1 P565260.2, FP565260.3, FP565260.4, FP565260.6, FP565260.7, FP565324.1, FP565324.2, FPGS, FPGT, FPGT-TNNI3K, FPR1, FPR2, FPR3, FRA10AC1, FRAS1, FRAT1, FRAT2, FREM1, FREM2, FREM3, FRG1, FRG2, FRG2B, FRG2C, FRK, FRMD1, FRMD3, FRMD4A, FRMD4B, FRMD5, FRMD6, FRMD7, FRMD8, FRMPD1, FRMPD2, FRMPD3, FRMPD4, FRRS1, FRRS1L, FRS2 、FRS3、FRY、FRYL、FRZB、FSBP、FSCB、FSCN1、FSCN2、FSCN3、FSD1、FSD1L、FSD2、FSHB、FSHR、FSIP1、FSIP2、FST、FSTL1、FSTL3、FSTL4、FSTL5、FTCD、FTCDNL1、FTH1、FTH L17、FTL、FTMT、FTO、FTSJ1、FTSJ3、FUBP1、FUBP3、FUCA1、FUCA2、FUK、FUNDC1、FUNDC2、FUOM、FURIN、FUS、FUT1、FUT10、FUT11、FUT2、FUT3、FUT4、FUT5、FUT6、FUT7、FUT 8、FUT9、FUZ、FXN、FXR1、FXR2、FXYD1、FXYD2、FXYD3、FXYD4、FXYD5、FXYD6、FXYD6-FXYD2、FXYD7、FYB1、FYB2、FYCO1、FYN、FYTTD1、FZD1、FZD10、FZD2、FZD3、FZD4 5. 、GABPA、GABPB1、GABPB2、GABRA1、GABRA2、GABRA3、GABRA4、GABRA5、GABRA6、GABRB1 、GABRB2、GABRB3、GABRD、GABRE、GABRG1、GABRG2、GABRG3、GABRP、GABRQ、GABRR1、GABRR2、GABRR3、GAD1、GAD2、GADD45A、GADD45B、GADD45G、GADD45GIP1、GADL1、GAGE1、G AGE10、GAGE12B、GAGE12C、GAGE12D、GAGE12E、GAGE12F、GAGE12G、GAGE12H、GAGE12J、GAGE13、GAGE2A、GAGE2E、GAK、GAL、GAL3ST1、GAL3ST2、GAL3ST3、GAL3ST4、GALC、GALE 、GALK1、GALK2、GALM、GALNS、GALNT1、GALNT10、GALNT11、GALNT12、GALNT13、GALNT 14、GALNT15、GALNT16、GALNT17、GALNT18、GALNT2、GALNT3、GALNT4、GALNT5、GALNT 6、GALNT7、GALNT8、GALNT9、GANLNTL5、GALTL6、GALP、GALR1、GALR2、GALR3、GALT、G AMT、GAN、GANAB、GANC、GAP43、GAPDH、GAPDHS、GAPT、GAPVD1、GAR1、GAREM1、GAREM2、 GARNL3、GARS、GART、GAS1、GAS2、GAS2L1、GAS2L2、GAS2L3、GAS6、GAS7、GAS8、GAST、 GATA1、GATA2、GATA3、GATA4、GATA5、GATA6、GATAD1、GATAD2A、GATAD2B、GATB、GATC、 GATD1、GATM、GATS、GBA、GBA2、GBA3、GBE1、GBF1、GBGT1、GBP1、GBP2、GBP3、GBP4、GB P5、GBP6、GBP7、GBX1、GBX2、GC、GCA、GCAT、GCC1、GCC2、GCDH、GCFC2、GCG、GCGR、GCH1 、GCHFR、GCK、GCKR、GCLC、GCLM、GCM1、GCM2、GCN1、GCNA、GCNT1、GCNT2、GCNT3、GCNT4、GCNT7、GCOM1、GC SAM、GCSAML、GCSH、GDA、GDAP1、GDAP1L1、GDAP2、GDE1、GDF1、GDF10、GDF11、GDF15、GDF2、GDF3、GDF5、GD F5OS、GDF6、GDF7、GDF9、GDI1、GDI2、GDNF、GDPD1、GDPD2、GDPD3、GDPD4" MIN4、GEMIN5、GEMIN6、GEMIN7、GEMIN8、GEN1、GET4、GFAP、GFER、GFI1、GFI1B、GFM1、GFM2、GFOD1、GFOD2 、GFPT1、GFPT2、GFRA1、GFRA2、GFRA3、GFRA4、GFRAL、GFY、GGA1、GGA2、GGA3、GGACT 、GGCT、GGCX、GGH、GGN、GGNBP2、GGPS1、GGT1、GGT2、GGT5、GGT6、GGT7、GGTLC1、GGTLC2、GGTLC 3、GH1、GH2、GHDC、GHITM、GHR、GHRH、GHRHR、GHRL、GHSR、GID4、GID8、GIF、GIGYF1、GIGYF2、GI MAP1、GIMAP1-GIMAP5、GIMAP2、GIMAP4、GIMAP5、GIMAP6、GIMAP7、GIMAP8、GIMD1、GIN1、GINM 1、GINS1、GINS2、GINS3、GINS4、GIP、GIPC1、GIPC2、GIPC3、GIPR、GIT1、GIT2、GJA1、GJA10、GJA 3、GJA4、GJA5、GJA8、GJA9、GJB1、GJB2、GJB3、GJB4、GJB5、GJB6、GJB7、GJC1、GJC2、GJC3、GJD2 、GJD3、GJD4、GJE1、GK、GK2、GK3P、GK5、GKAP1、GKN1、GKN2、GLA、GLB1、GLB1L、GLB1L2、GLB1L3 、GLCCI1、GLCE、GLDC、GLDN、GLE1、GLG1、GLI1、GLI2、GLI3、GLI4、GLIPR1、GLIPR1L1、GLIPR1L 2、GLIPR2、GLIS1、GLIS2、GLIS3、GLMN、GLMP、GLO1、GLOD4、GLOD5、GLP1R、GLP2R、GLRA1、GLRA2 、GLRA3、GLRA4、GLRB、GLRX、GLRX2、GLRX3、GLRX5、GLS、GLS2、GLT1D1、GLT6D1、GLT8D1、GLT8D2、GLTP、GLTPD2、GLUD1、GLUD2、G LUL、GLYAT、GLYATL1、GLYATL1P3、GLYATL2、GLYATL3、GLYCTK、GLYR1、GM2A、GMCL1、GMDS、GMEB1、GMEB2、GMFB、GMFG、GMIP、GML 、GMNC、GMNN、GMPPA、GMPPB、GMPR、GMPR2、GMPS、GNA11、GNA12、GNA13、GNA14、GNA1 5、GNAI1、GNAI2、GNAI3、GNAL、GNAO1、GNAQ、GNAS、GNAT1、GNAT2、GNAT3、GNAZ、GNB1 、GNB1L、GNB2、GNB3、GNB4、GNB5、GNE、GNG10、GNG11、GNG12、GNG13、GNG14、GNG2、GNG3、GNG4、GNG5、GNG7、GNG8、GNGT1、GNGT 2、GNL1、GNL2、GNL3、GNL3L、GNLY、GNMT、GNPAT、GNPDA1、GNPDA2、GNPNAT1、GNPTAB、GNPTG、GNRH1、GNRH2、GNRHR、GNS、GOLGA1 、GOLGA2、GOLGA3、GOLGA4、GOLGA5、GOLGA6A、GOLGA6B、GOLGA6C、GOLGA6D、GOLGA6L1、GOLGA6L10、GOLGA6L2、GOLGA6L22、GOLGA6L4、GOLGA6L6、GOLGA6L7P、GOLGA6L9、GOLGA7 ,GOLGA7B,GOLGA8A,GOLGA8B,GOLGA8F,GOLGA8G,GOLGA8H,GOLGA8J,GOLGA8K,GOLGA8M,GOLGA8N,GOLGA8O,GOLGA8Q,GOLGA8R,GOLGA8S,GOLGA8T,GOLGB1,GOLIM4,GOLM1,GOLPH3,GOLPH3L,GOLT1A,GOLT1B,GON4L,GON7,GOPC,GORAB,GORASP1,GORASP2,GOSR1,GOSR2,GOT1,GOT1L1,GOT2,GP1BA,GP1BB,GP2,GP5,GP6,GP9,GPA33,GPAA1,GPALPP1,GPAM,GPANK1,GPAT2,GPAT3,GPAT4,GPATCH1,GPATCH11,GPATCH2,GPATCH2L 、GPATCH3、GPATCH4、GPATCH8、GPBAR1、GPBP1、GPBP1L1、GPC1、GPC2、GPC3、GPC4、GPC5、GPC6、GPCPD1、GPD1、GPD1L、GPD2、GPER1、GPHA2、GPHB5、GPHN、GPI、GPIHBP1、GPKOW、GPLD1、GPM6A、GPM6B、GPN1、GPN2、GPN3、GPNMB、GPR1、GPR101、GPR107、GPR108、GPR119、GPR12、GPR132、GPR135、GPR137、GPR137B、GPR137C、GPR139、GPR141、GPR142 、GPR143、GPR146、GPR148、GPR149、GPR15、GPR150、GPR151、GPR152、GPR153、GPR155 、GPR156、GPR157、GPR158、GPR160、GPR161、GPR162、GPR17、GPR171、GPR173、GPR174 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4-39、IGHV4-4、IGHV4-59、IGHV4-61、IGHV4OR15-8、IGHV5-51、IG HV6-1, IGHV7-81, IGIP, IGKC, IGKJ1, IGKJ2, IGKJ3, IGKJ4, IGKJ5 、IGKV1-12、IGKV1-16、IGKV1-17、IGKV1-27、IGKV1-33、IGKV1-37、IGKV1-39、IGKV1-5 、IGKV1-6、IGKV1-8、IGKV1-9、IGKV1D-12、IGKV1D-13、IGKV1D-16、IGKV1D-17、IGKV1D-33、IGKV1D-37、IGKV1D-39、IGKV1D-42、IGKV1D-43、IGKV1D-8、IGKV1OR2-108、IGKV2-24、IGKV2-28、IGKV2-30、IGKV2-40、IGKV2D-24、IGKV2D-26、IGKV2D-28、IGKV2D-29、IGKV2D-30、IGKV2D-40、IGKV3-11、IGKV3-15、IGKV3-20、IGKV3-7、IGKV3D-11、IGKV3D-15、IGKV3D-20、IGKV3D-7、IGKV3OR2-268、IGKV4-1、IGKV5-2、IGKV6-21、IGKV6D-21、IGKV6D-41、IGLC1、IGLC2、IGLC3、IGLC7、IGLJ1、IGLJ2、IGLJ3、IGLJ4、IGLJ5、IGLJ6、IGLJ7 、IGLL1、IGLL5、IGLON5、IGLV10-54、IGLV11-55、IGLV1-36、IGLV1-40、IGLV 1-44、IGLV1-47、IGLV1-50、IGLV1-51、IGLV2-11、IGLV2-14、IGLV2-18、IGL V2-23, ILV2-33, ILV2-8, ILV3-1, ILV3-10, ILV3-12, ILV3-16, ILV3-19, ILV3-21, ILV3-22, ILV3-25, ILV3-27, ILV3-32, ILV3-9, ILV4 -3、IGLV4-60、IGLV4-69、IGLV5-37、IGLV5-45、IGLV5-48、IGLV5-52、IGLV6 -57、IGLV7-43、IGLV7-46、IGLV8-61、IGLV9-49、IGSF1、IGSF10、IGSF11、IGS F21, IGSF22, IGSF23, IGSF3, IGSF5, IGSF6, IGSF8, IGSF9, IGSF9B, IHH, IK, IKBIP, IKBKB, IKBKE, IKBKG, IKZF1, IKZF2, IKZF3, IKZF4, IKZF5, IL10, IL10 RA、IL10RB、IL11、IL11RA、IL12A、IL12B、IL12RB1、IL12RB2、IL13、IL13RA1 、IL13RA2、IL15、IL15RA、IL16、IL17A、IL17B、IL17C、IL17D、IL17F、IL17RA 、IL17RB、IL17RC、IL17RD、IL17RE、IL17REL、IL18、IL18BP、IL18R1、IL18RA P、IL19、IL1A、IL1B、IL1F10、IL1R1、IL1R2、IL1RAP、IL1RAPL1、IL1RAPL2、IL 1RL1、IL1RL2、IL1RN、IL2、IL20、IL20RA、IL20RB、IL21、IL21R、IL22、IL22R A1、IL22RA2、IL23A、IL23R、IL24、IL25、IL26、IL27、IL27RA、IL2RA、IL2RB、I L2RG、IL3、IL31、IL31RA、IL32、IL33、IL34、IL36A、IL36B、IL36G、IL36RN、I L37、IL3RA、IL4、IL4I1、IL4R、IL5、IL5RA、IL6、IL6R、IL6ST、IL7、IL7R、IL9、IL9R, ILDR1, ILDR2, ILF2, ILF3, ILK, ILKAP, ILVBL, IMMP1L, IMMP2L, I MMT、IMP3、IMP4、IMPA1、IMPA2、IMPACT、IMPAD1、IMPDH1、IMPDH2、IMP、 G1、IMPG2、INA、INAFM1、INAFM2、INAVA、INCA1、INCENP、INF2、ING1、ING2、ING3、IN G4、ING5、INHA、INHBA、INHBB、INHBC、INHBE、INIP、INMT、INMT-MINDY4、INO80、INO8 0B、INO80B-WBP1、INO80C、INO80D、INO80E、INPP1、INPP4A、INPP4B、INPP5A、INPP5B INPP5D、INPP5E、INPP5F、INPP5J、INPP5K、INPPL1、INS、INSC、INSIG1、INSIG2、INS -IGF2、INSL3、INSL4、INSL5、INSL6、INSM1、INSM2、INSR、INSRR、INTS1、INTS10、IN TS11、INTS12、INTS13、INTS14、INTS2、INTS3、INTS4、INTS5、INTS6、INTS6L、INTS7、 INTS8、INTS9、INTU、INVS、IP6K1、IP6K2、IP6K3、IPCEF1、IPMK、IPO11、IPO13、IPO4、 IPO5、IPO7、IPO8、IPO9、IPP、IPPK、IQANK1、IQCA1、IQCA1L、IQCB1、IQCC、IQCD、IQCE 、IQCF1、IQCF2、IQCF3、IQCF5、IQCF6、IQCG、IQCH、IQCJ、IQCJ-SCHIP1、IQCK、IQCM、 IQGAP1、IQGAP2、IQGAP3、IQSEC1、IQSEC2、IQSEC3、IQUB、IREB2、IRF1、IRF2、IRF2B P1, IRF2BP2, IRF2BPL, IRF3, IRF4, IRF5, IRF6, IRF7, IRF8, IRF9, IRGC, IRGM, IRGQ 、IRS1、IRS2、IRS4、IRX1、IRX2、IRX3、IRX4、IRX5、IRX6、ISCA1、ISCA2、ISCU、ISG15 、ISG20、ISG20L2、ISL1、ISL2、ISLR、ISLR2、ISM1、ISM2、ISOC1、ISOC2、ISPD、IST1 ISX, ISY1, ISY1-RAB43, ISYNA1, ITCH, ITFG1, ITFG2, ITGA1, ITGA10, ITGA11, ITG A2、ITGA2B、ITGA3、ITGA4、ITGA5、ITGA6、ITGA7、ITGA8、ITGA9、ITGAD、ITGAE、ITGAL 、ITGAM、ITGAV、ITGAX、ITGB1、ITGB1BP1、ITGB1BP2、ITGB2、ITGB3、ITGB3BP、ITGB4 ITGB5, ITGB6, ITGB7, ITGB8, ITGBL1, ITIH1, ITIH2, ITIH3, ITIH4, ITIH5, ITIH6, I TK、ITLN1、ITLN2、ITM2A、ITM2B、ITM2C、ITPA、ITPK1、ITPKA、ITPKB、ITPKC、ITPR1、I TPR2、ITPR3、ITPRIP、ITPRIPL1、ITPRIPL2、ITSN1、ITSN2、IVD、IVL、IVNS1ABP、IWS1 、IYD、IZUMO1、IZUMO1R、IZUMO2、IZUMO3、IZUMO4、JADE1、JADE2、JADE3、JAG1、JAG2 、JAGN1、JAK1、JAK2、JAK3、JAKMIP1、JAKMIP2、JAKMIP3、JAM2、JAM3、JAML、JARID2、JAZF 1、JCAD、JCHAIN、JDP2、JKAMP、JMJD1C、JMJD4、JMJD6、JMJD7、JMJD7-PLA2G4B、JMJD8、JM Y, JOSD1, JPH2, JPH3, JPH4, JPT1, JPT2, JRK, JRKL, JSRP1, JTB, JUN, JUNB. JUND、JUP、KAAG1、KALRN、KANK1、KANK2、KANK3、KANK4、KANSL1、KANSL1L、KANSL2、KANSL3 、KANTR、KARS、KAT14、KAT2A、KAT2B、KAT5、KAT6A、KAT6B、KAT7、KAT8、KATNA1、KATNAL1、KATNAL2、KATNB1、KATNBL1、KAZALD1、KAZN、KBTBD11、KBTBD11-OT1、KBTBD12、KBTBD13、KBTBD2、KBTBD3、KBTBD4、KBTBD6 BTBD7、KBTBD8、KCMF1、KCNA1、KCNA10、KCNA2、KCNA3、KCNA4、KCNA5、KCNA7、KCNAB1、KCNAB2、KCNAB3、KCNB1、KCNB2、KCNC1、KCNC2、KCNC3、KCNC4、KCND1、KCND2、KCND3、KCNE1、KCNE1B、KCNE2、KCNE3、KCNE4、KCNE5 、KCNF1、KCNG1、KCNG2、KCNG3、KCNG4、KCNH1、KCNH2、KCNH3、KCNH4、KCNH5、KCNH6、KCNH7、KCNH8、KCNIP1、KCNIP2、KCNIP3、KCN IP4、KCNJ1、KCNJ10、KCNJ11、KCNJ12、KCNJ13、KCNJ14、KCNJ15、KCNJ16、KCNJ18、KCNJ2、KCNJ3、KCNJ4、KCNJ5、KCNJ6、KCNJ8、KCNJ NJ9、KCNK1、KCNK10、KCNK12、KCNK13、KCNK15、KCNK16、KCNK17、KCNK18、KCNK2、KCNK3、KCNK4、KCNK5、KCNK6、KCNK7、KCNK9、KCNK NMA1、KCNMB1、KCNMB2、KCNMB3、KCNMB4、KCNN1、KCNN2、KCNN3、KCNN4、KCNQ1、KCNQ2、KCNQ3、KCNQ4、KCNQ5、KCNRG、KCNS1、KCNS2 、KCNS3、KCNT1、KCNT2、KCNU1、KCNV1、KCNV2、KCP、KCTD1、KCTD10、KCTD11、KCTD12、KCTD13、KCTD14、KCTD15、KCTD16、KCTD17、KCTD18、KCTD19、KCTD2、 KCTD20、KCTD21、KCTD3、KCTD4、KCTD5、KCTD6、KCTD7、KCTD8、KCTD9、KDELC1、KDELC2、KDELR1、KDELR2、KDELR3、KDF1、KDM1A、KDM1B、KDM2A、KDM2B、KDM 3A、KDM3B、KDM4A、KDM4B、KDM4C、KDM4D、KDM4E、KDM4F、KDM5A、KDM5B、KDM5C、KDM5D、KDM6A、KDM6B、KDM7A、KDM8、KDR、KDSR、KEAP1、KEL、KERA、KF45957 0.1、KHDC1、KHDC1L、KHDC3L、KHDRBS1、KHDRBS2、KHDRBS3、KHK、KHNYN、KHSRP、KIAA0040、KIAA0100、KIAA0141、KIAA0232、KIAA0319、KIAA0319L、KIAA0 355、KIAA0368、KIAA0391、KIAA0408、KIAA0513、KIAA0556、KIAA0586、KIAA0753、KIAA0825、KIAA0895、KIAA0895L、KIAA0907、KIAA0930、KIAA1024、KIAA0907 IAA1024L、KIAA1107、KIAA1109、KIAA1143、KIAA1147、KIAA1161、KIAA1191、KIAA1210、KIAA1211、KIAA1211L、KIAA1217、KIAA1257、KIAA1324、KIAA13 24L, KIAA1328, KIAA1456, KIAA1468, KIAA1522, KIAA1524, KIAA1549, KIAA1549L, KIAA1551, KIAA1586, KIAA1614, KIAA1644, KIAA1671, KIAA1683, KIAA1755, KIAA1841, KIAA1958, KIAA2012, KIAA2013, KIAA2026, KIDINS220, KIF11, KIF12, KIF13A, KIF13B, KIF14, KIF15, KIF16B, KIF17, KIF18A, KIF 18B, KIF19, KIF1A, KIF1B, KIF1BP, KIF1C, KIF20A, KIF20B, KIF21A, KIF21B, KIF22, KIF23, KIF24, KIF25, KIF26A, KIF26B, KIF27, KIF2A, KIF2B, KIF2C, KIF3A, KIF3B, KIF3C, KIF4A, KIF4B, KIF5A, KIF5B, KIF5C, KIF6, KIF7, KIF9, KIFAP3, KIFC1, KIFC2 KIFC3, KIN, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DL5B, KIR2DP1, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DL1, KIR3DL2, KIR3DL3, KIR3DP1, KIR3DS1, KIR3DX1, KIRREL1, KIRREL2, KIRREL3, KISS1, KISS1R, KIT, KITLG, KIZ, KL 、KLB、KLC1、KLC2、KLC3、KLC4、KLF1、KLF10、KLF11、KLF12、KLF13、KLF14、 KLF15、KLF16、KLF17、KLF18、KLF2、KLF3、KLF4、KLF5、KLF6、KLF7、KLF8、K LF9、KLHDC1、KLHDC10、KLHDC2、KLHDC3、KLHDC4、KLHDC7A、KLHDC7B、KLHD C8A、KLHDC8B、KLHDC9、KLHL1、KLHL10、KLHL11、KLHL12、KLHL13、KLHL14、K LHL15, KLHL17, KLHL18, KLHL2, KLHL20, KLHL21, KLHL22, KLHL23, KLHL24, KLHL25, KLHL26, KLHL28, KLHL29, KLHL3, KLHL30, KLHL31, KLHL32, KLHL3 3、KLHL34、KLHL35、KLHL36、KLHL38、KLHL4、KLHL40、KLHL41、KLHL42、KLH L5、KLHL6、KLHL7、KLHL8、KLHL9、KLK1、KLK10、KLK11、KLK12、KLK13、KLK14 、KLK15、KLK2、KLK3、KLK4、KLK5、KLK6、KLK7、KLK8、KLK9、KLKB1、KLLN、KLRB1、KLRC1 、KLRC2、KLRC3、KLRC4、KLRC4-KLRK1、KLRD1、KLRF1、KLRF2、KLRG1、KLRG2、KLRK1、KMO 、KMT2A、KMT2B、KMT2C、KMT2D、KMT2E、KMT5A、KMT5B、KMT5C、KNCN、KNDC1、KNG1、KNL1 、BUTTON1、KNSTRN、KNTC1、KP420437.1、KP420437.2、KP420437.3、KP420439.1、KP4204 40.1、KP420440.2、KP420440.3、KP420440.4、KP420440.5、KP420440.6、KP420440. 7、KP420440.8、KP420440.9、KP420441.1、KP420441.2、KP420441.3、KP420441.4、KP 420441.5、KP420442.2、KP420442.3、KP420443.1、KP420444.1、KP420444.2、KP420 444.3、KP420444.4、KP420444.5、KP420444.6、KP420444.7、KP420446.1、KP420446.2、KPNA1、KPNA2、KPNA3、KPNA4、KPNA5、KPNA6、KPNA7、KPNB1、KPRP、KPTN、KRAS、KRBA1、KRBA2、KRBOX1、KRBOX 4、KRCC1、KREMEN1、KREMEN2、KRI1、KRIT1、KRR1、KRT1、KRT10、KRT12、KRT13、KRT14、KRT15、KRT16、KRT17、KR T18、KRT19、KRT2、KRT20、KRT222、KRT23、KRT24、KRT25、KRT26、KRT27、KRT28、KRT3、KRT31、KRT32、KRT33A、K RT33B、KRT34、KRT35、KRT36、KRT37、KRT38、KRT39、KRT4、KRT40、KRT5、KRT6A、KRT6B、KRT6C、KRT7、KRT71、KR T72、KRT73、KRT74、KRT75、KRT76、KRT77、KRT78、KRT79、KRT8、KRT80、KRT81、KRT82、KRT83、KRT84、KRT85、KR T86、KRT9、KRTAP10-1、KRTAP10-10、KRTAP10-11、KRTAP10-12、KRTAP10-2、KRTAP10-3、KRTAP10-4、KRTAP10 -5、KRTAP10-6、KRTAP10-7、KRTAP10-8、KRTAP10-9、KRTAP1-1、KRTAP11-1、KRTAP12-1、KRTAP12-2、KRTAP12 -3、KRTAP12-4、KRTAP1-3、KRTAP13-1、KRTAP13-2、KRTAP13-3、KRTAP13-4、KRTAP1-4、KRTAP1-5、KRTAP15-1. 、KRTAP16-1、KRTAP17-1、KRTAP19-1、KRTAP19-2、KRTAP19-3、KRTAP19-4、KRTAP19-5、KRTAP19-6、KRTAP19-7、KRTAP19-8、KRTAP20 -1、KRTAP20-2、KRTAP20-3、KRTAP20-4、KRTAP2-1、KRTAP21-1、KRTAP21-2、KRTAP21-3、KRTAP2-2、KRTAP22-1、KRTAP22-2、KRTAP2-3 、KRTAP23-1、KRTAP2-4、KRTAP24-1、KRTAP25-1、KRTAP26-1、KRTAP27-1、KRTAP29-1、KRTAP3-1、KRTAP3-2、KRTAP3-3、KRTAP4-1、KRTAP4-11、KRTAP4-12、KRTAP4-16、KRTAP4-2 、KRTAP4-3、KRTAP4-4、KRTAP4-5、KRTAP4-6、KRTAP4-7、KRTAP4-8、KRTAP4-9、KRTAP5-1、KRTAP5-10、KRTAP5 -11、KRTAP5-2、KRTAP5-3、KRTAP5-4、KRTAP5-5、KRTAP5-6、KRTAP5-7、KRTAP5-8、KRTAP5-9、KRTAP6-1、KRTAP 6-2、KRTAP6-3、KRTAP7-1、KRTAP8-1、KRTAP9-1、KRTAP9-2、KRTAP9-3、KRTAP9-4、KRTAP9-6、KRTAP9-7、KRTA P9-8、KRTAP9-9、KRTCAP2、KRTCAP3、KRTDAP、KSR1、KSR2、KTI12、KTN1、KU645196.1、KU645196.2、KU645196.3 、KU645196.4、KU645196.5、KU645196.6、KU645196.7、KU645196.8、KU645196.9、KU645197.1、KU645197.2 、KU645197.3、KU645197.4、KU645197.5、KU645198.1、KXD1、KY、KYAT1、KYAT3、KYNU、L1CAM、L1TD1、L2HGDH 、L34079.1、L3HYPDH、L3MBTL1、L3MBTL2、L3MBTL3、L3MBTL4、LACC1、LACRT、LACTB、LACTB2、LACTBL1、LAD1、LAG3、LAGE3、LAIR1、LAIR2、LALBA、LAMA1、LAMA2、LAMA4、LAMA5、LAMB1、LAMB1 、LAMC2、LAMC3、LAMP1、LAMP2、LAMP3、LAMP5、LAMTOR1、LAMTOR2、LAMTOR3、LAMTOR4、LAMTOR5、LANCL1、LANCL2、LANCL3、LAP3、LAPTM4A、LAPTM4B、LAPTM5、LARGE1、LARGE2 、LARP1、LARP1B、LARP4、LARP4B、LARP6、LARP7、LARS、LARS2、LAS1L、LASP1、LAT、L AT2、LATS1、LATS2、LAX1、LAYN、LBH、LBHD1、LBP、LBR、LBX1、LBX2、LCA5、LCA5L、LCA T、LCE1A、LCE1B、LCE1C、LCE1D、LCE1E、LCE1F、LCE2A、LCE2B、LCE2C、LCE2D、LCE3A、LCE3B、LCE3C、LCE3D、LCE3E、LCE4A、LCE5A、LCE6A、LCK、LCLAT1、LCMT1、LCMT2、LCN1、LCN10、LCN12、LCN15、LCN2、LCN6、LCN8、LCN9、LCNL1、LCOR、LCORL、LCP1、LCP2、LCT、LCTL、LDAH、LDB1、LDB2、LDB3、LDHA、LDHAL6A、LDHAL6B、LDHB、LDHC、LDHD、LDLR、LDLRAD1、LDLRAD2、LDLRAD3、LDLRAD4、LDLRAP1、LDOC1、LEAP2、LECT2、LEF1、LEFTY1、LEFTY2、LEKR1、LELP1、LEMD1、LEMD2、LEMD3、LENEP、LENG1、LENG8、LENG9、LEO1、LEP、LEPR、LEPROT、LEPROTL1、LETM1、LETM2、LETMD1、LEUTX、LEXM、LFNG、LGALS1、LGALS12、LGALS13、LGALS14、LGALS16、LGALS2、LGALS3、LGALS3BP、LGALS4、LGALS7、LGALS7B、LGALS8、LGALS9、LGALS9B、LGALS9C、LGALSL、LGI1、LGI2、LGI3、LGI4、LGMN、LGR4、LGR5、LGR6、LGSN、LHB、LHCGR、LHFPL1、LHFPL2、LHFPL3、LHFPL4、LHFPL5、LHFPL6、LHPP、LHX1、LHX2、LHX3、LHX4、LHX5、LHX6、LHX8、LHX9、LIAS、LIF、LIFR、LIG1、LIG3、LIG4、LILRA1、LILRA2、LILRA3、LILRA4、LILRA5、LILRA6、LILRB1、LILRB2、LILRB3 、LILRB4、LILRB5、LIM2、LIMA1、LIMCH1、LIMD1、LIMD2、LIME1、LIMK1、LIMK2、LIMS1 、LIMS2、LIMS3、LIMS4、LIN28A、LIN28B、LIN37、LIN52、LIN54、LIN7A、LIN7B、LIN7C ,LIN9, LINC00094, LINC00116, LINC00282, LINC00672, LINC00675, LINC00694, LINC00854, LINC00890, LINC00959, LINC01125, LINC01556, LINC02210-CRHR1, LINGO1, LINGO2, LINGO3, LINGO4, LINS1, LIPA, LIPC, LIPE, LIPF, LIPG, LIPH, LIPI, LIPJ, LIPK, LIPM, LIPN, LIPT1, LIPT2, LITAF, LIX1, LIX1L, LKAAEAR1, LLGL1, LLGL2, LLPH, LMAN1, LMAN1L, LMAN2, LMAN2L, LMBR1, LMBR1L, LMBRD1, LMBRD2, LMCD1, LMF1, LMF2, LMLN 、LMNA、LMNB1、LMNB2、LMNTD1、LMNTD2、LMO1、LMO2、LMO3、LMO4、LMO7、LMO7DN、LMOD1、LMOD2、LMOD3、LMTK2、LMTK3、LMX1A、LMX1B、LNP1、LNPEP、LNPK、LNX1、LNX2、LO000005.1、LONP1、LONP2、LONRF1、LONRF2、LONRF3、LOR、LOX、LOXHD1、LOXL1、LOXL2、LOXL3、LOXL4、LPA、LPAR1、LPAR2、LPAR3、LPAR4、LPAR5、LPAR6、LPCAT1、LPCAT2、LPCAT3、LPCAT4、LPGAT1、LPIN1、LPIN2、LPIN3、LPL、LPO、LPP、LPXN、LRAT、LRBA、LRCH1、LRCH2、LRCH3、LRCH4、LRCOL1、LRFN1、LRFN2、LRFN3、LRFN4、LRFN5、LRG1、LRGUK、LRIF1、LRIG1、LRIG2、LRIG3、LRIT1、LRIT2、LRIT3、LRMDA、LRMP、LRP1、LRP10、LRP11、LRP12、LRP1B、LRP2、LRP2BP、LRP3、LRP4、LRP5、LRP5L、LRP6、LRP8、LRPAP1、LRPPRC、LRR1、LRRC1、LRRC10、LRRC10B、LRRC14、LRRC14B、LRRC15、LRRC17、LRRC18、LRRC19、LRRC2、LRRC20、LRRC23、LRRC24、LRRC25、LRRC26、LRRC27、LRRC28、LRRC29、LRRC3、LRRC30、LRRC31、LRRC32、LRRC34、LRRC36、LRRC37A、LRRC37A2、LRRC37A3、LRRC37B、LRRC38、LRRC39、LRRC3B、LRRC3C、LRRC4、LRRC40、LRRC41、LRRC42、LRRC43、LRRC45、LRRC46、LRRC47、LRRC49、LRRC4B、LRRC4C、LRRC52、LRRC53、LRRC55、LRRC56、LRRC57、LRRC58、LRRC59、LRRC6、LRRC61、LRRC63、LRRC66、LRRC69、LRRC7、LRRC70、LRRC71、LRRC72、LRRC73、LRRC74A、LRRC74B、LRRC75A、LRRC75B、LRRC8A、LRRC8B、LRRC8C、LRRC8D、LRRC8E、LRRC9、LRRCC1、LRRD1、LRRFIP1、LRRFIP2、LRRIQ1、LRRIQ 3、LRRIQ4、LRRK1、LRRK2、LRRN1、LRRN2、LRRN3、LRRN4、LRRN4CL、LRRTM1、LRRTM2、LRRTM3、LRRTM4、LRSAM1、LRT M1、LRTM2、LRTOMT、LRWD1、LSAMP、LSG1、LSM1、LSM10、LSM11、LSM12、LSM14A、LSM14B、LSM2、LSM3、LSM4、LSM5、L SM6、LSM7、LSM8、LSMEM1、LSMEM2、LSP1、LSR、LSS、LST1、LTA、LTA4H、LTB、LTB4R、LTB4R2、LTBP1、LTBP2、LTBP3、 LTBP4、LTBR、LTC4S、LTF、LTK、LTN1、LTV1、LUC7L、LUC7L2、LUC7L3、LUM、LURAP1、LURAP1L、LUZP1、LUZP2、LUZP 4、LUZP6、LVRN、LXN、LY6D、LY6E、LY6G5B、LY6G5C、LY6G6C、LY6G6D、LY6G6E、LY6G6F、LY6H、LY6K、LY6L、LY75、LY 75-CD302、LY86、LY9、LY96、LYAR、LYG1、LYG2、LYL1、LYN、LYNX1、LYPD1、LYPD2、LYPD3、LYPD4、LYPD5、LYPD6、LY PD6B、LYPD8、LYPLA1、LYPLA2、LYPLAL1、LYRM1、LYRM2、LYRM4、LYRM7、LYRM9、LYSMD1、LYSMD2、LYSMD3、LYSMD4、 、LYST、LYVE1、LYZ、LYZL1、LYZL2、LYZL4、LYZL6、LZIC、LZTFL1 、LZTR1、LZTS1、LZTS2、LZTS3、M1AP、M6PR、MAATS1、MAB21L1、MA B21L2、MAB21L3、MACC1、MACF1、MACROD1、MACROD2、MAD1L1、MAD2L1、MAD2L1BP、MAD2L2、MADCAM1、MADD、MAEA、MAEL、MAF、MAF1 MAGE、MAFB、MAFF、MAFG、MAFK、MAG、MAGEA1、MAGEA10、MAGEA11、MAGEA12、MAGEA2、MAGEA2B、MAGEA3、MAGEA4、MAGEA4、MAGEA4、MAGEA4 MAGEB1、MAGEB10、MAGEB16、MAGEB17、MAGEB18、MAGEB2、MAGEB3、MAGEB4、MAGEB5、MAGEB6EC1、MAGEB6P1 MAGEC2. MAGEL2、MAGI1、MAGI2、MAGI3、MAGIX、MAGOH、MAGOHB、MAGT1、MAIP1、MAJIN、MAK、MAK16、MAL 、MAL2、MALL、MALRD1、MALSU1、MALT1、MAMDC2、MAMDC4、MAML1、MAML2、MAML3、MAMLD1、MAMSTR、 MAN1A1、MAN1A2、MAN1B1、MAN1C1、MAN2A1、MAN2A2、MAN2B1、MAN2B2、MAN2C1、MANBA、MANBAL、MANEA、MANEAL、MANF、MANSC1、MANSC4、MAOA、MAOB、MAP10、MAP1A、MAP1B、MAP1LC3A、MAP1LC3B、MAP1LC3B2、MAP1LC3C、MAP1S、MAP2、MAP2K1、MAP2K2、MAP2K3、MAP2K4、MAP2K5、MAP2K6、MAP2K7、MAP3K1、MAP3K10、MAP3K11、MAP3K12、MAP3K13、MAP3K14、MAP3K15、MAP3K19、MAP3K2、MAP3K20、MAP3K21、MAP3K3、MAP3K4、MAP3K5、MAP3K6、MAP3K7、MAP3K7CL、MAP3K8、MAP3K9、MAP4、MAP4K1、MAP4K2、MAP4K3、MAP4K4、MAP4K5、MAP6、MAP6D1、MAP7、MAP7D1、MAP7D2、MAP7D3、MAP9、MAPK1、MAPK10、MAPK11、MAPK12、MAPK13、MAPK14、MAPK15、MAPK1IP1L、MAPK3、MAPK4、MAPK6、MAPK7、MAPK8、MAPK8IP1、MAPK8IP2、MAPK8IP3、MAPK9、MAPKAP1、MAPKAPK2、MAPKAPK3、MAPKAPK5、MAPKBP1、MAPRE1、MAPRE2、MAPRE3、MAPT、MARC1、MARC2、MARCH1、MARCH10、MARCH11、MARCH2、MARCH3、MARCH4、MARCH5、MARCH6、MARCH7、MARCH8、MARCH9、MARCKS、MARCKSL1、MARCO、MARF1、MARK1、MARK2、MARK3、MARK4、MARS、MARS2、MARVELD1、MARVELD2、MARVELD3、MAS1、MAS1L、MASP1、MASP2、MAST1、MAST2、MAST3、MAST4、MASTL、MAT1A、MAT2A、MAT2B、MATK、MATN1、MATN2、MATN3、MATN4、MATR3、MAU2、MAVS、MAX、MAZ、MB、MB21D1、MB21D2、MBD1 、MBD2、MBD3、MBD3L1、MBD3L2、MBD3L2B、MBD3L3、MBD3L4、MBD3L5、MBD4、MBD5、MBD6 、MBIP、MBL2、MBLAC1、MBLAC2、MBNL1、MBNL2、MBNL3、MBOAT1、MBOAT2、MBOAT4、MBOAT7、MBP、MBTD1、MBTPS1、MBTPS 2, MC1R, MC2R, MC3R, MC4R, MC5R, MCAM, MCAT, MCC, MCCC1, MCCC2, MCCD1, MCEE, MCEMP1, MCF2, MCF2L, MCF2L2, MCFD2 MCHR1, MCHR2, MCIDAS, MCL1, MCM10, MCM2, MCM3AP, MCM4, MCM5, MCM6, MCM7, MCM8, MCM9, MCMBP, MCMDC2, MC OLN1, MCOLN2, MCOLN3, MCPH1, MCRIP1, MCRIP2, MCRS1, MCTP1, MCTP2, MCTS1, MCU, MCUB, MCUR1, MDC1, MDFI, MDFIC. MDFIC2, MDGA1, MDGA2, MDH1, MDH1B, MDH2, MDK, MDM1, MDM2, MDM4, MDN1, MDP1, MDS2, ME1, ME2, ME3, MEA1, MEAF6.M ECOM, MECP2, MECR, MED1, MED10, MED11, MED12, MED12L, MED13, MED13L, MED14, MED14OS, MED15, MED16, MED17, MED 18. MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED28, MED29, MED30, MED31, MED4, MED6, MED 7. MED8, MED9, MEDAG, MEF2A, MEF2B, MEF2C, MEF2D, MEFV, MEGF10, MEGF11, MEGF6, MEGF8, MEGF9, MEI1, MEI4, MEIG1 、MEIKIN、MEIOB、MEIOC、MEIS1、MEIS2、MEIS3、MELK、MELTF、MEMO1、MEN1、ME OX1、MEOX2、MEP1A、MEP1B、MEPCE、MEPE、MERTK、MESD、MESP1、MESP2、MEST、ME T、METAP1、METAP1D、METAP2、METRN、METRNL、METTL1、METTL11B、METTL12、M ETTL13、METTL14、METTL15、METTL16、METTL17、METTL18、METTL21A、METTL21 C、METTL22、METTL23、METTL24、METTL25、METTL26、METTL27、METTL2A、METT L2B、METTL3、METTL4、METTL5、METTL6、METTL7A、METTL7B、METTL8、METTL9、M EX3A、MEX3B、MEX3C、MEX3D、MFAP1、MFAP2、MFAP3、MFAP3L、MFAP4、MFAP5、MF F、MFGE8、MFHAS1、MFN1、MFN2、MFNG、MFRP、MFSD1、MFSD10、MFSD11、MFSD12、M FSD13A、MFSD14A、MFSD14B、MFSD14C、MFSD2A、MFSD2B、MFSD3、MFSD4A、MFSD 4B、MFSD5、MFSD6、MFSD6L、MFSD7、MFSD8、MFSD9、MGA、MGAM、MGAM2、MGARP、MG AT1、MGAT2、MGAT3、MGAT4A、MGAT4B、MGAT4C、MGAT4D、MGAT5、MGAT5B、MGEA5 、MGLL、MGME1、MGMT、MGP、MGRN1、MGST1、MGST2、MGST3、MIA、MIA3、MIA-RAB4B 、MIB1、MIB2、MICA、MICAL1、MICAL2、MICAL3、MICALCL、MICALL1、MICALL2、M ICB、MICU1、MICU2、MICU3、MID1、MID1IP1、MID2、MIDN、MIEF1、MIEF2、MIEN1、 MIER1、MIER2、MIER3、MIF、MIF4GD、MIGA1、MIGA2、MIIP、MILR1、MINDY1、MIN DY2、MINDY3、MINDY4、MINDY4B、MINK1、MINOS1、MINOS1-NBL1、MINPP1、MIOS、MIOX、MIP、MIPEP、MIPOL1、MIS12、MIS18A、MIS18BP1、MISP、MISP3、MITD1、MITF、MIXL1、MKI67、MKKS、MKL1、MKL2、MK LN1、MKNK1、MKNK2、MKRN1、MKRN2、MKRN2OS、MKRN3、MKS1、MKX、MLANA、MLC1、MLEC、MLF1、MLF2、MLH1、MLH3、MLIP、MLK L, MLLT1, MLLT10, MLLT11, MLLT3, MLLT6, MLN, MLNR, MLPH, MLST8, MLX, MLXIP, MLXIPL, MLYCD, MMAA, MMAB, MMACHC, MMADHC, MMD, MMD2, MME, MMEL1, MMGT1, MMP1, MMP10, MMP11, MMP12, MMP13, MMP14, MMP15, MMP16, MMP17, MMP19, MMP2 MMP20, MMP21, MMP23B, MMP24, MMP24-AS1, MMP25, MMP26, MMP27, MMP28, MMP3, MMP7, MMP8, MMP9, MMRN1, MMRN2, MMS19, MMS22L, MN1, MNAT1, MND1, MNDA, MNS1, MNT, MNX1, MOAP1, MOB1A, MOB1B, MOB2, MOB3A, MOB 3B、MOB3C、MOB4、MOBP、MOCOS、MOCS1、MOCS2、MOCS3、MOG、MOGAT1、MOGAT2、MOGAT3、MOGS、MOK、MON1A、MO N1B、MON2、MORC1、MORC2、MORC3、MORC4、MORF4L1、MORF4L2、MORN1、MORN2、MORN3、MORN4、MORN5、MOS、MOS PD1、MOSPD2、MOSPD3、MOV10、MOV10L1、MOXD1、MPC1、MPC1L、MPC2、MPDU1、MPDZ、MPEG1、MPG、MPHOSPH10、 MPHOSPH6、MPHOSPH8、MPHOSPH9、MPI、MPIG6B、MPL、MPLKIP、MPND、MPO、MPP1、MPP2、MPP3、MPP4、MPP5、MPP 6, MPP7, MPPE1, MPPED1, MPPED2, MPRIP, MPST, MPV17, MPV17L, MPV17L2, MPZ, MPZL1, MPZL2, MPZL3, MR1, MRAP, MRAP2, MRAS, MRC1, MRC2, MRE11, MREG, MRFAP1, MRFAP1L1, MRGBP, MRGPRD, MRGPRE, MRGPRF, MRGPRG 、MRGPRX1、MRGPRX2、MRGPRX3、MRGPRX4、MRI1、MRLN、MRM1、MRM2、MRM3、MR NIP、MRO、MROH1、MROH2A、MROH2B、MROH5、MROH6、MROH7、MROH7-TTC4、MROH 8、MROH9、MRPL1、MRPL10、MRPL11、MRPL12、MRPL13、MRPL14、MRPL15、MRPL1 6、MRPL17、MRPL18、MRPL19、MRPL2、MRPL20、MRPL21、MRPL22、MRPL23、MRPL 24、MRPL27、MRPL28、MRPL3、MRPL30、MRPL32、MRPL33、MRPL34、MRPL35、MRP L36、MRPL37、MRPL38、MRPL39、MRPL4、MRPL40、MRPL41、MRPL42、MRPL43、MR PL44、MRPL45、MRPL46、MRPL47、MRPL48、MRPL49、MRPL50、MRPL51、MRPL52、 MRPL53、MRPL54、MRPL55、MRPL57、MRPL58、MRPL9、MRPS10、MRPS11、MRPS12 MRP S27、MRPS28、MRPS30、MRPS31、MRPS33、MRPS34、MRPS35、MRPS36、MRPS5、MRPS6、MRPS7、MRPS9、MRRF、MRS2、MRTO4、MRVI1、MS4A1 、MS4A10、MS4A12、MS4A13、MS4A14、MS4A15、MS4A2、MS4A3、MS4A4A、MS4A4E、MS4A5、MS 4A6A、MS4A6E、MS4A7、MS4A8、MSANTD1、MSANTD2、MSANTD3、MSANTD3-TMEFF1、MSANTD4 MSC, MSGN1, MSH2, MSH3, MSH4, MSH5, MSH5-SAPCD1, MSH6, MSI1, MSI2, MSL1, MSL2 MSL3, MSLN, MSLNL, MSMB, MSMO1, MSMP, MSN, MSR1, MSRA, MSRB1, MSRB2, MSRB3, MSS51, MST1, MST1R, MS TN, MSTO1, MSX1, MSX2, MT1A, MT1B, MT1E, MT1F, MT1G, MT1H, MT1HL1, MT1M, MT1X, MT2A, MT3, MT4, MTA1 TA2, MTA3, MTAP, MT-ATP6, MT-ATP8, MTBP, MTCH1, MTCH2, MTCL1, MT-CO1, MT-CO2, MT-CO3, MTCP1, MT-CY B、MTDH、MTERF1、MTERF2、MTERF3、MTERF4、MTF1、MTF2、MTFMT、MTFP1、MTFR1、MTFR1L、MTFR2、MTG1、MTG2 、MTHFD1、MTHFD1L、MTHFD2、MTHFD2L、MTHFR、MTHFS、MTHFSD、MTIF2、MTIF3、MTM1、MTMR1、MTMR10、MTMR11、MTMR12、MTMR14、MTMR2、MTMR3、MTMR4、MTMR6、MTMR7、MTMR8、MTMR9、MT-ND1、MT-ND2、MT-ND3、MT-ND4、MT-ND4L、MT-ND5、MT-ND6、MTNR1A、MTNR1B、MTO1、MTOR、MTPAP、MTPN、MTR、MTRF1、MTRF1L、MTRNR2L1、MTRNR2L10、MTRNR2L11、MTRNR2L12、MTRNR2L13、MTRNR2L3、MTRNR2L4、MTRNR2L5、MTRNR2L6、MTRNR2L7、MTRNR2L8、MTRR、MTSS1、MTSS1L、MTTP、MTURN、MTUS1、MTUS2、MTX1、MTX2、MTX3、MUC1、MUC12、MUC13、MUC15、MUC16、MUC17、MUC2、MUC20、MUC21、MUC22、MUC3A、MUC4、MUC5AC、MUC5B、MUC6、MUC7、MUCL1、MUL1、MUM1、MUM1L1、MUS81、MUSK、MUSTN1、MUT、MUTYH、MVB12A、MVB12B、MVD、MVK、MVP、MX1、MX2、MXD1、MXD3、MXD4、MXI1、MXRA5、MXRA7、MXRA8、MYADM、MYADML2、MYB、MYBBP1A、MYBL1、MYBL2、MYBPC1、MYBPC2、MYBPC3、MYBPH、MYBPHL 、MYC、MYCBP、MYCBP2、MYCBPAP、MYCL、MYCN、MYCT1、MYD88、MYDGF、MYEF2、MYEOV、MYF5、MYF6、MYH1、MYH10、MYH11、MYH13、MYH14、MYH15、MYH2、MYH3、MYH4、MYH6、MYH7 MYH7B、MYH8、MYH9、MYL1、MYL10、MYL12A、MYL12B、MYL2、MYL3、MYL4、MYL5、MYL6B、MYL6 7、MYL9、MYLIP、MYLK、MYLK2、MYLK3、MYLK4、MYLPF、MYMK、MYMX、MYNN、MYO10、MYO15A、MYO15B MYO16、MYO18A、MYO18B、MYO19、MYO1A、MYO1B、MYO1C、MYO1D、MYO1E、MYO1F、MYO1G、MYO1H、MYO 3A、MYO3B、MYO5A、MYO5B、MYO5C、MYO6、MYO7A、MYO7B、MYO9A、MYO9B、MYOC、MYOCD、MYOCOS、MYO D1、MYOF、MYOG、MYOM1、MYOM2、MYOM3、MYOT、MYOZ1、MYOZ2、MYOZ3、MYPN、MYPOP、MYRF、MYRFL、M YRIP. BP2L2、N4BP3、N6AMT1、A10、A11、A15、A16、A20、A25、A30、A35、A38、A4 0、NAA50、NAA60、NAA、NAME2、NAMEDL1、NASD2、NAB1、NAB2、NABP1、NABP2、NACA、NACA2 、NACAD、NACC1、NACC2、NADK、NADK2、NADSYN1、NAE1、NAF1、NAGA、NAGK、NAGLU、NAGP A、NAGS、NAIF1、NAIP、NALCN、NAMPT、NANOG、NANOGNB、NANOGP8、NANOS1、NAN OS2、NANOS3、NANP、NANS、NAP1L1、NAP1L2、NAP1L3、NAP1L4、NAP1L5、NAPA、NA PB、NAPEPLD、NAPG、NAPRT、NAPSA、NARF、NARFL、NARS、NARS2、NASP、NAT1、NA T10、NAT14、NAT16、NAT2、NAT6、NAT8、NAT8B、NAT8L、NAT9、NATD1、NAV1、NAV2 、NAV3、NAXD、NAXE、NBAS、NBDY、NBEA、NBEAL1、NBEAL2、NBL1、NBN、NBPF1、NB PF10、NBPF11、NBPF12、NBPF14、NBPF15、NBPF19、NBPF20、NBPF26、NBPF3、NBP F4、NBPF6、NBPF9、NBR1、NCALD、NCAM1、NCAM2、NCAN、NCAPD2、NCAPD3、NCAPG 、NCAPG2、NCAPH、NCAPH2、NCBP1、NCBP2、NCBP2-AS2、NCBP2L、NCBP3、NCCRP1、 NCDN、NCEH1、NCF1、NCF2、NCF4、NCK1、NCK2、NCKAP1、NCKAP1L、NCKAP5、NCKA P5L、NCKIPSD、NCL、NCLN、NCMAP、NCOA1、NCOA2、NCOA3、NCOA4、NCOA5、NCOA6、 NCOA7、NCOR1、NCOR2、NCR1、NCR2、NCR3、NCR3LG1、NCS1、NCSTN、NDC1、NDC80 、NDE1、NDEL1、NDFIP1、NDFIP2、NDN、NDNF、NDOR1、NDP、NDRG1、NDRG2、NDRG3、 NDRG4、NDST1、NDST2、NDST3、NDST4、NDUFA1、NDUFA10、NDUFA11、NDUFA12、N DUFA13、NDUFA2、NDUFA3、NDUFA4、NDUFA4L2、NDUFA5、NDUFA6、NDUFA7、NDUFA 8、NDUFA9、NDUFAB1、NDUFAF1、NDUFAF2、NDUFAF3、NDUFAF4、NDUFAF5、NDUFA F6、NDUFAF7、NDUFAF8、NDUFB1、NDUFB10、NDUFB11、NDUFB2、NDUFB3、NDUFB4、NDUFB5、NDUFB6、NDUFB7、NDUFB8、NDUFB9、NDUFC1、NDUFC2、NDUFC2-KCTD14、NDUFS1、NDUFS2、NDUFS3、NDUFS4、NDUFS5、NDUFS6、NDUFS7、NDUFS8、NDUFV1、NDUFV2、NDUFV3、NEB、NEBL、NECAB1、NECAB2、NECAB3、NECAP1、NECAP2、NECTIN1、NECTIN2、NECTIN3、NECTIN4、NEDD1、NEDD4、NEDD4L、NEDD8、NEDD8-MDP1、NEDD9、NEFH、NEFL、NEFM、NEGR1、NEIL1、NEIL2、NEIL3、NEK1、NEK10、NEK11、NEK2、NEK3、NEK4、NEK5、NEK6、NEK7、NEK8、NEK9、NELFA、NELFB、NELFCD、NELFE、NELL1、NELL2、NEMF、NEMP1、NEMP2、NENF、NEO1、NEPRO、NES、NET1、NETO1、NETO2、NEU1、 、NEU2、NEU3、NEU4、NEURL1、NEURL1B、NEURL2、NEURL3、NEURL4、NEUROD1、NEUROD2、NEUROD4、NEUROD6、NEUROG1、NEUROG2、NEUROG3、NEXMIF、NEXN、NF1、NF2、NFAM1、NFASC、NFAT5、NFATC1、NFATC2、NFATC2IP、NFATC3、NFATC4、NFE2、NFE2L1、NFE2L2、NFE2L3 、NFE4、NFIA、NFIB、NFIC、NFIL3、NFIX、NFKB1、NFKB2、NFKBIA、NFKBIB、NFKBID、NFKBI E、NFKBIL1、NFKBIZ、NFRKB、NFS1、NFU1、NFX1、NFXL1、NFYA、NFYB、NFYC、NGB、NGDN、NG EF, NGF, NGFR, NGLY1, NGRN, NHEJ1, NHLH1, NHLH2, NHLRC1, NHLRC2, NHLRC3, NHLRC4, NHP2, NHS, NHSL1, NHSL2, NICN1, NID1, NID2, NIF3L1, NIFK, NIM1K, NIN, NINJ1, NINJ2, N INL、NIP7、NIPA1、NIPA2、NIPAL1、NIPAL2、NIPAL3、NIPAL4、NIPBL、NIPSNAP1、NIPSNA P2、NIPSNAP3A、NIPSNAP3B、NISCH、NIT1、NIT2、NKAIN1、NKAIN2、NKAIN3、NKAIN4、NKAP 、NKAPL、NKD1、NKD2、NKG7、NKIRAS1、NKIRAS2、NKPD1、NKRF、NKTR、NKX1-1、NKX1-2、NK NKX2-1 6-2、NKX6-3、NLE1、NLGN1、NLGN2、NLGN3、NLGN4X、NLGN4Y、NLK、NLN、NLRC3、NLRC4、NLRC5、NLRP1、NLRP10、NLRP11、NLRP12、NLRP13、NLRP14、NLRP2、NLRP2B、NLRP3、NLRP4、NLRP5、NLRP6、N LRP7、NLRP8、NLRP9、NLRX1、NMB、NMBR、NMD3、NME1、NME1-NME2、NME2、NME3、NME4、NME5、NME6、NME7、NME8、NME9、NMI、NMNAT1、NMNAT2、NMNAT3、NMRAL1、NMRK1、NMRK2、NMS、NMT1、NMT2、NMU 、NMUR1、NMUR2、NNAT、NNMT、NNT、NOA1、NOB1、NOBOX、NOC2L、NOC3L、NOC4L、NOCT、NOD1、NOD2、NODAL、NOG、NOL10、NOL11、NOL12、NOL3、NOL4、NOL4L、NOL6、NOL7、NOL8、NOL9、NOLC1、NOM1、NO 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R11G2、OR11H1、OR11H12、OR11H2、OR11H4、OR11H6、OR11H7、OR11L1、OR12D1、OR12D2、OR12D3、OR13A1、OR13C2、OR13C3、OR13C4、OR13C5、OR13C7、OR13C8 、OR13C9、OR13D1、OR13F1、OR13G1、OR13H1、OR13J1、OR14A16、OR14A2、OR14C36、OR14I1、OR14J1、OR14K1、OR1A1、OR1A2、OR1B1、OR1C1、OR1D2、OR1D5、OR15 R1E1、OR1E2、OR1F1、OR1G1、OR1I1、OR1J1、OR1J2、OR1J4、OR1K1、OR1L1、OR1L3、OR1L4、OR1L6、OR1L8、OR1M1、OR1N1、OR1N2、OR1P1、OR1Q1、OR1S1、OR1S2OR2A1, OR2A12, OR2A14, OR2A2, OR2A25, OR2A4, OR2A42, OR2A5, OR2A7, OR2AE1, OR2AG1, OR2AG2, OR2AJ1, OR2AK2, OR2AP1, OR2AT4, OR2B11, OR2B2, OR2B3, OR2B6 OR2C1, OR2C3, OR2D2, OR2D3, OR2F1, OR2F2, OR2G2, OR2G3, OR2G6, OR2H1, OR2H2, OR2J1, OR2J2, OR2J3, OR2K2, OR2L13, OR2L2, OR2L3, OR2L5, OR2L8, OR2M2, OR2M 3、OR2M4、OR2M5、OR2M7、OR2S2、OR2T1、OR2T10、OR2T11、OR2T12、OR2T2、OR2T27、 OR2T29、OR2T3、OR2T33、OR2T34、OR2T35、OR2T4、OR2T5、OR2T6、OR2T7、OR2T8、OR 2V1, OR2V2, OR2W1, OR2W3, OR2Y1, OR2Z1, OR3A1, OR3A2, OR3A3, OR4A15, OR4A16, OR4A47, OR4A5, OR4A8, OR4B1, OR4C11, OR4C12, OR4C13, OR4C15, OR4C16, OR4C3 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、PAX4、PAX5、PAX6、PAX7、PAX8、PAX9、PAXBP1、PAXIP1、PAXX、PBDC1、PBK、PBLD、PBOV1、PBRM1、PBX1、PBX2、PBX3、PBX4、PBXIP1、PC、PCBD1、PCBD2、PCBP1、PCBP2、PCBP3、PCBP4、PCCA、PCCB、PCDH1、PCDH10、PCDH11X、PCDH11Y、PCDH12、PCDH15、PCDH17、PCDH18、PCDH19、PCDH20、PCDH7、PCDH8、PCDH9、PCDHA1、PCDHA10、PCDHA11、PCDHA12、PCDHA13、PCDHA2、PCDHA3、PCDHA4、PCDHA5、PCDHA6、PCDHA7、PCDHA8、PCDHA9、PCDHAC1 、PCDHAC2、PCDHB1、PCDHB10、PCDHB11、PCDHB12、PCDHB13、PCDHB14、PCDHB15、PCDHB16、PCDHB2、PCDHB3、PCDHB4、PCDHB5、PCDHB6、PCDHB7、PCDHB8、PCDHB9、PCDHGA1、PCDHGA10、PCDHGA11、PCDHGA12、PCDHGA2、PCDHGA3、PCDHGA4、PCDHGA5、PCDHGA6、PCDHGA7、PCDHGA8、PCDHGA9、PCDHGB1、PCDHGB2、PCDHGB3、PCDHGB4、PCDHGB5、PCDHGB6、PCDHGB7、PCDHGC3、PCDHGC4、PCDHGC5、PCED1A、PCED1B、PCF11、PCGF1、PCGF2、PCGF3、PCGF5、PCGF6、PCID2、PCIF1、PCK1、PCK2、PCLAF、PCLO、PCM1、PCMT1、PCMTD1、PCMTD2、PCNA、PCNP、PCNT、PCNX1、PCNX2、PCNX3、PCNX4、PCOLCE、PCOLCE2、PCOTH、PCP2、PCP4、PCP4L1、PCSK1、PCSK1N、PCSK2、PCSK4、PCSK5、PCSK6、PCSK7、PCSK9、PCTP、PCYOX1、PCYOX1L、PCYT1A、PCYT1B、PCYT2、PDAP1、PDC、PDCD1、PDCD10、PDCD11、PDCD1LG2、PDCD2、PD 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Claims

[Claim 1] The need to find a bifunctional compound that is a protein-degrading agent useful as a therapeutic agent.

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