Molecular GLUE degrader compounds and uses thereof

Abstract

Described herein are molecular glue degrader compounds that bind to both a target protein and a RING E3 Ubiquitin Ligase, as well as related compositions and methods of use, e.g., for degradation of the target protein and / or the treatment of a disease, disorder, or condition.

Description

[0001] MOLECULAR GLUE DEGRADER COMPOUNDS AND USES THEREOF

[0002] CLAIM OF PRIORITY

[0003] This application claims priority to U.S. Application No. 63 / 638163, filed on April 24, 2024, and U.S. Application No. 63 / 640584, filed on April 30, 2024. The disclosure of each of the foregoing applications is incorporated herein by reference in its entirety.

[0004] STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

[0005] The subject matter of this application was made with government support under Grant CA240981 awarded by the National Institutes of Health and Grant 2127788 awarded by the National Science Foundation. The government has certain rights in the invention.

[0006] FIELD OF THE DISCLOSURE

[0007] Described herein are molecular glue degrader compounds that bind to both a target protein and a RING E3 Ubiquitin Ligase, as well as related compositions and methods of use, e.g., for degradation of the target protein and / or the treatment of a disease, disorder, or condition.

[0008] BACKGROUND

[0009] Proteasome-mediated degradation of unneeded or damaged proteins plays an important role in maintaining regular cellular functions, such as cell survival, proliferation and growth. In particular, the Ubiquitin-Proteasome Pathway (UPP) is central to multiple cellular processes, and if defective or imbalanced, leads to pathogenesis of a variety of diseases. Targeted protein degradation (TPD) has arisen as a powerful therapeutic modality for eliminating classically undruggable disease-causing proteins through ubiquitination and proteasome-mediated degradation. Two major approaches for TPD include heteromolecular glue Proteolysis Targeting Chimeras (PROTACs) or molecular glue degraders, each which result in the ubiquitination and degradation of the target protein in a proteasomal dependent manner. While much is understood about PROTAC structure and mechanism, the mechanism of action of certain molecular glue degrader compounds is less clear. As such, there is a need for a deeper understanding of the chemical design principles for converting protein-targeting ligands into molecular glue degraders and related methods of use thereof. SUMMARY

[0010] The present disclosure features molecular glue degrader compounds, as well as pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers thereof, capable of inducing degradation of a target protein. In one aspect, the present disclosure features a molecular glue degrader compound comprising: (i) a Target Ligand capable of binding to a target protein; and (ii) a RINGE3 Ligase Binder capable of binding to a RING E3 ubiquitin ligase. In an embodiment, the molecular glue degrader compound further comprises a bridge domain linking the Target Ligand and the RING E3 Ligase Binder. In another embodiment, the molecular glue degrader compound does not comprise a bridge domain linking the Target Ligand and the RING E3 Ligase Binder, i.e., the Target Ligand and the RING E3 Ligase Binder are directly bound to one another. In an embodiment, the molecular glue degrader compounds have the structure of Formula (I): f - \

[0011] Target Ligand RING E3 Ligase Binder - - - ' (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein (i) the Target Ligand is capable of binding to a target protein; (ii) Bridge is absent or a linker; and (iii) the RING E3 Ligase Binder is capable of binding to a RING E3 ubiquitin ligase (e.g., RNF126 or BCA2). In an embodiment, the RING E3 Ligase Binder binds to RNF126 E3 ubiquitin ligase, BCA2 E3 ubiquitin ligase, LRSAM1 E3 ubiquitin ligase, RNF40 E3 ubiquitin ligase, MID2 E3 ubiquitin ligase, RNF219 E3 ubiquitin ligase, or RNF14 E3 ubiquitin ligase. In an embodiment, the RING E3 Ligase Binder binds to RNF126 E3 ubiquitin ligase. In an embodiment, the RING E3 Ligase Binder binds to a cysteine residue within a RING E3 ubiquitin ligase. In an embodiment, the RING E3 Ligase Binder covalently binds to a cysteine residue within a RING E3 ubiquitin ligase. In an embodiment, the RING E3 Ligase Binder binds to a non-catalytic cysteine residue within RNF126 (e.g., C32). In an embodiment, the RING E3 Ligase Binder binds to BCA2 E3 ubiquitin ligase. In an embodiment, the RING E3 Ligase Binder binds to LRSAM1 E3 ubiquitin ligase. In an embodiment, the RING E3 Ligase Binder binds to MID2 E3 ubiquitin ligase. In an embodiment, the RING E3 Ligase Binder binds to RNF40 E3 ubiquitin ligase. In an embodiment, the RING E3 Ligase Binder binds to RNF219 E3 ubiquitin ligase. In an embodiment, the RING E3 Ligase Binder binds to RNF14 E3 ubiquitin ligase. In an embodiment, the RING E3 Ligase Binder comprises an electrophilic moiety (e.g., C2-10 alkenylene moiety). In an embodiment, the RING E3 Ligase Binder comprises a comprises a cinnamamide moiety or a fumarate moiety.

[0012] In an embodiment, the target protein selected from a tyrosine kinase, a serine / threonine kinase, a bromodomain-containing protein, an epigenetic protein, and a misfolded protein. In an embodiment, the target protein is selected from AR, BCL-2 / BCL, BCL-XL, BCR-ABL, BRD2, BRD3, BRD4, BRD9, BRDT, BTK, BUB1, BUB1B, c-ABL, CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11B, CDK12, CDK13, CDK14, CDK15, CDK16, CDK17, CDK18, CDK19, CDK20, CHEK1, CKS1B, CKS2, CSNK1A1, CSNK1E, CTNNB1, DSTYK, EEF2K, ER, ETNK1, FASTKD5, HRAS, ITPKB, KRAS, LRKK2, MAPKAPK2 (MK2), MARK2, MAP3K2, MELK, MYC, MYCN, NEK6, NRAS, PANK2, PANK3, PDE5, PHKA1, PHKA2, PKN2, PLK1, PTK6, RI0K2, SKP2, SMARCA2, SMARCA4, STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6, TK1, TTK, and UCK2, or a mutant, isoform, or fragment thereof. For example, the target protein may be AR or a mutant or isoform thereof, e.g., AR H874Y, AR F876L, AR T877A, AR W741L / C, AR-V1, AR- V2, AR-V3, AR-V4, AR-V5, AR-V6, AR-V7, AR-V9, or ARv567es. For example, the target protein may be KRAS or a mutant or isoform thereof, e.g., KRAS4A, KRAS4B, KRAS G12A, KRAS G12C, KRAS G12D, KRAS G12S, KRAS G12V, or KRASG13D. In another example, the target protein may be AR or a mutant or isoform thereof, e.g., AR H874Y, AR F876L, AR T877A, or AR W741L / C.

[0013] In another aspect, the present disclosure features molecular glue degrader compounds having the structure of Formula (II): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0014] X is O or S;

[0015] Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7; Target Ligand

[0016] R1is

[0017] L1is a linker selected from the group of alkyl, heteroalkyl, C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I);

[0018] Target Ligand comprises a moiety capable of binding to a target protein;

[0019] R2is selected from the group consisting of hydrogen and Ci-6 alkyl; or

[0020] R1and R2together with the atoms to which they are attached form a 5- to 10-membered heteroaryl or a 3 - to 12-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9;

[0021] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl;

[0022] R4and R?are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;

[0023] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0024] R6aand R6b, together with the atoms to which they are attached, form an oxo group;

[0025] R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl;

[0026] — L Target Ligand

[0027] R8is

[0028] L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R15is independently selected from hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0029] RBis hydrogen or C1-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, or 4.

[0030] In an embodiment, the molecular glue degrader compounds have the structure of Formula (Lb): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein X is O or S; Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10-membered heteroaryl, a 3- to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl; L2is a linker substituted with 0-4 occurrences of R9; Target Ligand comprises a moiety capable of binding to a target protein; R2aand R2bare each independently hydrogen, C1-6 alkyl, and C3-8 cycloalkyl; R3aand R3bare each independently selected from the group consisting of hydrogen, - OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, Ci-6 haloalkoxyl, and C3- 8 cycloalkyl; or R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci- 6 haloalkyl, and C1-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0031] In another aspect, the present disclosure features a method of treating a target disease, disorder, or condition (e.g., a protein-mediated disorder, disease, or condition) in a patient comprising administering to the patient any of the compounds described herein, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. In an embodiment, the disorder is selected from a respiratory disorder, a proliferative disorder, an autoimmune disorder, an autoinflammatory disorder, an inflammatory disorder, a neurological disorder, and an infectious disease or disorder. In an embodiment, the disorder is a proliferative disorder. In an embodiment, the proliferative disorder is cancer.

[0032] Another embodiment is a method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of described herein, or a pharmaceutically acceptable salt thereof.

[0033] Another embodiment is a pharmaceutical composition comprising any of the compounds described herein, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable carrier.

[0034] Another embodiment is a method of treating a respiratory disorder, a proliferative disorder, an autoimmune disorder, an autoinflammatory disorder, an inflammatory disorder, a neurological disorder, and an infectious disease or disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof. In an embodiment, the disorder is a proliferative disorder. In an embodiment, the proliferative disorder is cancer.

[0035] Another embodiment is the use of a compound described herein, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof in the preparation of a medicament for treating a respiratory disorder, a proliferative disorder, an autoimmune disorder, an autoinfl ammatory disorder, an inflammatory disorder, a neurological disorder, and an infectious disease or disorder in a subject in need thereof. Exemplary embodiments of the present disclosure are described in further detail herein, including in the Drawings, Description, Examples, and Claims.

[0036] DETAILED DESCRIPTION

[0037] Described herein are compounds and related pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof useful as molecular glue degrader compounds. The compounds contain both a Target Ligand domain for binding to a target protein and a RING E3 Ligase Binder domain for recruitment of a RING E3 ubiquitin ligase domain to provide for degradation of the target protein. The present disclosure further features compositions of molecular glue degrader compounds as well as methods of preparation and use thereof.

[0038] Molecular Glue Degrader Compounds

[0039] The present disclosure features a molecular glue degrader compound having the structure of Formula (I):

[0040] ( 'l ( —

[0041] Target Ligand - 1 Bridge ! - RING E3 Ligase Binder

[0042] ' - 'v z' - - - ' (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein: (i) the Target Ligand is capable of binding to a target protein; (ii) Bridge is absent or a linker; and (iii) the RING E3 Ligase Binder is capable of binding to a RING E3 ubiquitin ligase (e.g., RNF126 or BCA2). In an embodiment, the Target Ligand is a small molecule capable of binding a target protein, e.g., in a non-covalent manner. In an embodiment, Bridge is absent. In an embodiment, Bridge is a linker, e.g., a linker described herein. In an embodiment, the RING E3 Ligase Binder is capable of covalently binding to a RING E3 ubiquitin ligase. In an embodiment, the RING E3 Ligase Binder comprises an electrophilic moiety, e.g., a C2-10 alkenylene moiety. In an embodiment, the RING E3 Ligase Binder is capable of binding to a cysteine residue within the RING E3 ubiquitin ligase, e.g., a non-catalytic cysteine residue within the RING E3 ubiquitin ligase.

[0043] In an embodiment, the molecular glue degrader compounds have the structure of Formula (II): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: X is O or S; Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7; R1is ; L1is a linker selected from the group of alkyl, heteroalkyl, C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloalkyl- NRB-C(0)-CO-4 heteroalkylene*-, -C2-5 cycloalkyLNRB-C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I); Target Ligand comprises a moiety capable of binding to a target protein; R2is selected from the group consisting of hydrogen and Ci-6 alkyl; or R1and R2together with the atoms to which they are attached form a 5 - to 10-membered heteroaryl or a 3 - to 12-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxy alkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; R7are each independently selected from the group consisting of- OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; R8is — IS Target Ligand

[0044] ; L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene-*, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R15is independently selected from hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; RBis hydrogen or C1-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, or 4.

[0045] In an embodiment, the molecular glue degrader compounds have a structure of Formula (II-a): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: X is O or S; Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10-membered heteroaryl, a 3- to 12- membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl, optionally substituted with one

[0046] Target Ligand or more R7; R1is ; L1is a linker selected from the group of alkyl, heteroalkyl, C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I); Target Ligand comprises a moiety capable of binding to a target protein; R2is selected from the group consisting of hydrogen and Ci-6 alkyl; or R1and R2together with the atoms to which they are attached form a 5- to 10-membered heteroaryl or a 3- to 12- membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl; R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; R8is ; L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene-*, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R13, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R15is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; RBis hydrogen or Ci-6 alkyl; and p is 0, 1, 2, 3, or 4.

[0047] In an embodiment, the molecular glue degrader compounds have the structure of Formula (II-b): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein X is O or S; Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10-membered heteroaryl, a 3- to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl; L2is a linker substituted with 0-4 occurrences of R9; Target Ligand comprises a moiety capable of binding to a target protein; R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; R3aand R3bare each independently selected from the group consisting of hydrogen, - OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3- 8 cycloalkyl; or R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci- 6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0048] In an embodiment, the molecular glue degrader compounds have the structure of Formula (III): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: X is O or S; Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7; Target Ligand comprises a moiety capable of binding to a target protein; L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene-*, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, C1-6 alkyl, and C1-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; R7are each independently selected from the group consisting of- OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R15is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; RBis hydrogen or Ci-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, or 4.

[0049] As generally described herein for compounds of Formula (II), (III), and subformulas therein, Ring A is selected from the group consisting of aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each of which is optionally substituted with one or more R7.

[0050] As generally described herein for compounds of Formula (II)-(III), Ring A is selected from the group consisting of aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each of which is optionally substituted with one or more R7.

[0051] In some embodiments, Ring A is selected from the group consisting of 6- to 10- membered aryl, a 5- to 10-membered heteroaryl, a 3 - to 12-membered cycloalkyl, and a 3- to 12- membered heterocycloalkyl, each of which is optionally substituted with one or more R7.

[0052] In some embodiments, Ring A is a monocyclic ring, e.g., monocyclic cycloalkyl, monocyclic heterocyclyl, monocyclic aryl, or monocyclic heteroaryl. The monocyclic ring may be saturated, partially unsaturated, or fully unsaturated (e.g., aromatic).

[0053] In some embodiments, Ring A is a bicyclic ring, e.g., bicyclic cycloalkyl, bicyclic heterocyclyl, bicyclic aryl, or bicyclic heteroaryl. The bicyclic ring may be saturated, partially unsaturated, or fully unsaturated (e.g., aromatic). In some embodiments, Ring A is a bicyclic ring comprising a fused, bridged, or spiro ring system.

[0054] In some embodiments, Ring A is an aryl or heteroaryl ring, optionally substituted with 1- 4 occurrences of R7. In some embodiments, Ring A is a monocyclic aryl ring. In some embodiments, Ring A is a bicyclic aryl ring. In some embodiments, Ring A is a 6- to 10- membered aryl ring (e.g., phenyl). In some embodiments, Ring A is a 6-membered aryl ring.

[0055] In some embodiments, Ring A is an 8-membered aryl ring. In some embodiments, Ring A is a 10-membered aryl ring. In some embodiments, Ring A is phenyl.

[0056] In some embodiments, Ring A is an aryl ring, fused with a heterocycloalkyl ring. In some embodiments, Ring A is an aryl ring, optionally substituted with two or more R7, wherein two R7on adjacent atoms together with the atoms to which they are attached form an optionally substituted heterocycloalkyl ring. In some embodiments, Ring A is an aryl ring, optionally substituted with two or more R7, wherein two R7on adjacent atoms together with the atoms to which they are attached form an optionally substituted heterocycloalkyl ring containing 1 or 2 O or N atoms. In some embodiments, Ring A is an aryl ring, optionally substituted with two or more R7, wherein two R7on adjacent atoms together with the atoms to which they are attached form an optionally substituted heterocycloalkyl ring containing 1 oxygen atom. In some embodiments, Ring A is an aryl ring, optionally substituted with two or more R7, wherein two R7on adjacent atoms together with the atoms to which they are attached form an optionally substituted heterocycloalkyl ring containing 2 O or N atoms.

[0057] In some embodiments, Ring A is a heteroaryl ring. In some embodiments, Ring A is a monocyclic heteroaryl ring. In some embodiments, Ring A is a bicyclic heteroaryl ring. In some embodiments, Ring A is a 5- to 10-membered heteroaryl ring. In some embodiments, Ring A is a 5-membered heteroaryl ring (e.g., thiophenyl). In some embodiments, Ring A is a 6-membered heteroaryl ring (e.g., pyridyl). In some embodiments, Ring A is a heteroaryl ring containing O, S, or N. In some embodiments, Ring A is a monocyclic heteroaryl ring containing one O or S atom.

[0058] In some embodiments, Ring A is a heterocycloalkyl ring. In some embodiments, Ring A is a monocyclic heterocycloalkyl ring. In some embodiments, Ring A is a bicyclic heterocycloalkyl ring. In some embodiments, Ring A is a 3 - to 12-membered heterocycloalkyl ring. In some embodiments, Ring A is a heterocycloalkyl ring, wherein the ring is fused, bridged, or spiro. In some embodiments, Ring A is a heterocycloalkyl ring, containing 1, 2, or 3 heteroatoms. In some embodiments, Ring A is a heterocycloalkyl ring, containing 1, 2, or 3 N, O, or S atoms. In some embodiments, Ring A is a heterocycloalkyl ring, containing 1, 2, or 3 N atoms. In some embodiments, Ring A is a monocyclic heterocycloalkyl ring, containing 1 or 2 N atoms. In some embodiments, Ring A is a heterocycloalkyl ring, optionally fused to an aryl ring. In some embodiments, Ring A is a heterocycloalkyl ring, containing at least one O and one N atom. In some embodiments, Ring A is a bicyclic spiro heterocycloalkyl ring.

[0059] In some embodiments, Ring A is a cycloalkyl ring. In some embodiments, Ring A is a monocyclic or bicyclic cycloalkyl ring. In some embodiments, Ring A is a monocyclic cycloalkyl ring. In some embodiments, Ring A is a 3- to 12-membered cycloalkyl ring. In some embodiments, Ring A is a 5-membered cycloalkyl ring. In some embodiments, Ring A is a cycloalkyl ring, optionally containing one double bond.

[0060] 5

[0061] 10

[0062]

[0063] As generally described herein, X is O or S. In some embodiments, X is O. In some embodiments, X is S.

[0064] — Target Ligand

[0065] As generally described herein, R1is , wherein L1is a linker

[0066] (e.g., a linker as described herein), and the Target Ligand comprises a moiety capable of binding to a target protein.

[0067] As generally described herein, L1is a linker selected from the group of alkyl, heteroalkyl, C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRD-C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I). In some embodiments, L1is a linker selected from the group of C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R1?, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I).

[0068] In some embodiments, L1is selected from -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB- C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein

[0069] * denotes the point of attachment of L1to the Target Ligand in Formula (I).

[0070] In some embodiments, L1is alkyl, optionally substituted with one or more R15. In some embodiments, L1is heteroalkyl, optionally substituted with one or more R15. In some embodiments, L1is C2-5 cycloalkyl, optionally substituted with one or more R15In some embodiments, L1is -C2-5 cycloalkyl-NRB-*, optionally substituted with one or more R15, wherein

[0071] * denotes the point of attachment of L1to the Target Ligand in Formula (I). In some embodiments, L1is -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I). In some embodiments, L1is -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I). In some embodiments, L1is -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O- *, optionally substituted with one or more R13, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I).

[0072] In some embodiments, L1is -C4 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, optionally substituted with one or more R1?, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I). In some embodiments, L1is -C4 cycloalkyl-NRB-C(O)-Ci alkylene-O-*, optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I). In some embodiments, L1is -C4 cycloalkyl-NRB-C(O)-CH2-O- *, optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I). In some embodiments, L1is -cyclobutyl-NRB-C(O)-CH2-O-*, optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I). In some embodiments, L1is -cyclobutyl-NH-C(O)-CH2-O-*, optionally substituted with one or more R1?, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I).

[0073] As generally described herein, R2is selected from the group consisting of hydrogen and Ci-6 alkyl; or R1and R2together with the atoms to which they are attached form a heteroaryl or a heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9.

[0074] In some embodiments, R2is hydrogen. In some embodiments, R2is Ci-6 alkyl. In some embodiments, R2is Ci alkyl (e.g., CH3, methyl). In some embodiments, R2is C2 alkyl (e.g., ethyl). In some embodiments, R2is C3 alkyl (e.g., propyl). In some embodiments, R2is C4 alkyl (e.g., butyl). In some embodiments, R2is C5 alkyl (e.g., pentyl). In some embodiments, R2is Ce alkyl (e.g., hexyl). In some embodiments, R2is hydrogen, methyl, or ethyl. In some embodiments, R2is hydrogen or CH3.

[0075] In some embodiments, R1and R2together with the atoms to which they are attached form a heteroaryl or a heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 5- to 10-membered heteroaryl or a 3- to 12-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 5 - to 8-membered heteroaryl or a 3- to 9-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 5- to 6-membered heteroaryl or a 5- to 8-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 5-membered heteroaryl or a 6- membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 5- to 10-membered heteroaryl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 5-membered heteroaryl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 6-membered heteroaryl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 7-membered heteroaryl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 8-membered heteroaryl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 9-membered heteroaryl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 10-membered heteroaryl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 5- to 8-membered heteroaryl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 5 - to 6-membered heteroaryl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a pyridyl ring, substituted with one R8, and optionally substituted with 1-4 occurrences of R9.

[0076] In some embodiments, R1and R2together with the atoms to which they are attached form a 3- to 12-membered heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 3 - to 9-membered heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 5- to 8-membered heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 3 -membered heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 4-membered heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 5- membered heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 6-membered heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 7-membered heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 8-membered heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. In some embodiments, R1and R2together with the atoms to which they are attached form a 9-membered heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9.

[0077] In some embodiments, R1and R2together with the atoms to which they are attached form a monocyclic or bicyclic heterocycloalkyl ring. In some embodiments, R1and R2together with the atoms to which they are attached form a monocyclic heterocycloalkyl ring. In some embodiments, R1and R2together with the atoms to which they are attached form a bicyclic heterocycloalkyl ring. In some embodiments, R1and R2together with the atoms to which they are attached form a 6- or 7-membered heterocycloalkyl ring (e.g. piperazinyl). In some embodiments, R1and R2together with the atoms to which they are attached form a heterocycloalkyl ring, comprising 1, 2, or 3 heteroatoms. In some embodiments, R1and R2together with the atoms to which they are attached form a heterocycloalkyl ring, comprising 2 or 3 heteroatoms. In some embodiments, R1and R2together with the atoms to which they are attached form a heterocycloalkyl ring, comprising 2 N atoms. In some embodiments, R1and R2together with the atoms to which they are attached form a heterocycloalkyl ring, comprising 2 N atoms and one or more O atoms.

[0078] In some embodiments, R1and R2together with the atoms to which they are attached form a fused, bridged, or spiro heterocycloalkyl ring. In some embodiments, R1and R2together with the atoms to which they are attached form a fused bicyclic heterocycloalkyl ring. In some embodiments, R1and R2together with the atoms to which they are attached form a fused bicyclic heterocycloalkyl ring, comprising 1, 2, or 3 heteroatoms. Tn some embodiments, R1and R2together with the atoms to which they are attached form a fused bicyclic heterocycloalkyl ring, comprising 2 N atoms. In some embodiments, R1and R2together with the atoms to which they are attached form a bridged heterocycloalkyl ring. In some embodiments, R1and R2together with the atoms to which they are attached form a bridged heterocycloalkyl ring, comprising 1, 2, or 3 heteroatoms. In some embodiments, R1and R2together with the atoms to which they are attached form a bridged heterocycloalkyl ring, comprising 2 heteroatoms. In some embodiments, R1and R2together with the atoms to which they are attached form a bridged heterocycloalkyl ring, comprising 2 N atoms. In some embodiments, R1and R2together with the atoms to which they are attached form a spiro heterocycloalkyl ring. In some embodiments, R1and R2together with the atoms to which they are attached form a spiro heterocycloalkyl ring, comprising 1, 2, or 3 heteroatoms. In some embodiments, R1and R2together with the atoms to which they are attached form a spiro heterocycloalkyl ring, comprising 2 or 3 heteroatoms. In some embodiments, R1and R2together with the atoms to which they are attached form a spiro heterocycloalkyl ring, comprising 2 N atoms. In some embodiments, R1and R2together with the atoms to which they are attached form a spiro heterocycloalkyl ring, comprising 2 N atoms and one or more O atoms.

[0079] In some embodiments, R1and R2together with the atoms to which they are attached form some embodiments, R1and R2together with the atoms to which they are attached form a heterocycloalkyl ring selected from: . In some embodiments, R1and R2together with the atoms to which they are attached form a heterocycloalkyl ring selected from: In some embodiments, R1and R2together with the atoms to which they are attached form a heterocycloalkyl ring selected from: some embodiments, R1and R2together with the atoms to which they are attached form a heterocycloalkyl ring selected from: As generally described herein, R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl. In an embodiment, R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, and Ci-6 alkyl. In an embodiment, R3aand R3bare each independently selected from the group consisting of hydrogen and Ci-6 alkyl. In an embodiment, R3aand R3bare each independently hydrogen.

[0080] In an embodiment, R3ais selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl. In an embodiment, R3ais selected from hydrogen, -OH, halogen, and Ci-6 alkyl. In an embodiment, R3ais selected from hydrogen and Ci-6 alkyl. In an embodiment, R3ais hydrogen. In an embodiment, R3ais -OH. In an embodiment, R3ais halogen. In an embodiment, R3ais Ci-6 alkyl. In an embodiment, R3ais Ci- 6 alkoxyl. In an embodiment, R3ais Ci-6 hydroxyalkyl. In an embodiment, R3ais Ci-6 haloalkyl. In an embodiment, R3ais Ci-6 haloalkoxyl. In an embodiment, R3ais C3-8 cycloalkyl.

[0081] In an embodiment, R3bis selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl. In an embodiment, R3bis selected from hydrogen, -OH, halogen, and Ci-6 alkyl. In an embodiment, R3bis selected from hydrogen and Ci-6 alkyl. In an embodiment, R3bis hydrogen. In an embodiment, R3bis -OH. In an embodiment, R3bis halogen. In an embodiment, R3bis Ci-6 alkyl. In an embodiment, R3bis Ci- 6 alkoxyl. In an embodiment, R3bis Ci-6 hydroxyalkyl. In an embodiment, R3bis Ci-6 haloalkyl. In an embodiment, R3bis Ci-6 haloalkoxyl. In an embodiment, R3bis C3-8 cycloalkyl.

[0082] As generally described herein, R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl. In an embodiment, R4and R are each independently selected from the group consisting of hydrogen, -OH, halogen, and Ci-6 alkyl. In an embodiment, R4and R5are each independently selected from the group consisting of hydrogen, halogen, and Ci-6 alkyl. In an embodiment, R4and R5are each independently selected from the group consisting of hydrogen and Ci-6 alkyl. In an embodiment, R4and R5are each independently hydrogen.

[0083] In an embodiment, R4is selected from the group consisting of hydrogen, -OH, halogen, - CN, Ci-6 alkyl, and Ci-6 haloalkyl. In an embodiment, R4is selected from the group consisting of hydrogen, -OH, halogen, and Ci-6 alkyl. In an embodiment, R4is selected from the group consisting of hydrogen, halogen, and Ci-6 alkyl. In an embodiment, R4is selected from the group consisting of hydrogen and Ci-6 alkyl. In an embodiment, R4is hydrogen. In an embodiment, R4is -OH. In an embodiment, R4is halogen. In an embodiment, R4is -CN. In an embodiment, R4is Ci-6 alkyl. In an embodiment, R4is Ci-6 haloalkyl.

[0084] In an embodiment, R5is selected from the group consisting of hydrogen, -OH, halogen, - CN, Ci-6 alkyl, and Ci-6 haloalkyl. In an embodiment, R5is selected from the group consisting of hydrogen, -OH, halogen, and Ci-6 alkyl. In an embodiment, R?is selected from the group consisting of hydrogen, halogen, and Ci-6 alkyl. In an embodiment, R5is selected from the group consisting of hydrogen and Ci-6 alkyl. In an embodiment, R5is hydrogen. In an embodiment, R5is -OH. In an embodiment, R5is halogen. In an embodiment, R is -CN. In an embodiment, R is Ci-6 alkyl. In an embodiment, R5is Ci-6 haloalkyl.

[0085] As generally described herein, R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group. In an embodiment, R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl. In an embodiment, R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, and Ci-6 alkyl. In an embodiment, R6aand R6bare each independently selected from the group consisting of hydrogen and Ci-6 alkyl. In an embodiment, R6aand R6bare each independently hydrogen. In an embodiment, R6aand R6b, together with the atoms to which they are attached, form an oxo group.

[0086] In some embodiments, R6ais hydrogen. In some embodiments, R6ais -OH. In some embodiments, R6ais halogen. In some embodiments, R6ais -Cl. In some embodiments, R6ais -F. In some embodiments, R6ais -Br. In some embodiments, R6ais -I. In some embodiments, R6ais Ci-6 alkyl. In some embodiments, R6ais -CH3. In some embodiments, R6ais -Me. In some embodiments, R6ais -Et. In some embodiments, R6ais propyl. In some embodiments, R6ais Ci-6 alkoxyl. In some embodiments, R6ais -OMe. In some embodiments, R6ais -OEt. In some embodiments, R6ais Ci-6 hydroxyalkyl. In some embodiments, R6ais Ci-6 haloalkyl. In some embodiments, R6ais -CF3. In some embodiments, R6ais -CFH2. In some embodiments, R6ais - CF2H. In some embodiments, R6ais Ci-6 haloalkoxyl. In some embodiments, R6ais -OCF3. In some embodiments, R6ais C3-8 cycloalkyl. In some embodiments, R6ais cyclopropyl. In some embodiments, R6ais cyclobutyl. In some embodiments, R6ais cyclopentyl. In some embodiments, R6ais cyclohexyl.

[0087] In some embodiments, R6bis hydrogen. In some embodiments, R6bis -OH. In some embodiments, R6bis halogen. In some embodiments, R6bis -Cl. In some embodiments, R6bis -F. In some embodiments, R6bis -Br. In some embodiments, R6bis -I. In some embodiments, R6bis Ci-6 alkyl. In some embodiments, R6bis -CH3. In some embodiments, R6bis -Me. In some embodiments, R6bis -Et. In some embodiments, R6bis propyl. In some embodiments, R6bis C1-6 alkoxyl. In some embodiments, R6bis -OMe. In some embodiments, R6bis -OEt. In some embodiments, R6bis C1-6 hydroxyalkyl. In some embodiments, R6bis C1-6 haloalkyl. In some embodiments, R6bis -CF3. In some embodiments, R6bis -CFH2. In some embodiments, R6bis - CF2H. In some embodiments, R6bis C1-6 haloalkoxyl. In some embodiments, R6bis -OCF3. In some embodiments, R6bis C3-8 cycloalkyl. In some embodiments, R6bis cyclopropyl. In some embodiments, R6bis cyclobutyl. In some embodiments, R6bis cyclopentyl. In some embodiments, R6bis cyclohexyl.

[0088] As generally described herein, R7are each independently selected from the group consisting of -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl. In an embodiment, each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, and Ci-6 haloalkyl. In an embodiment, each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkoxyl, and Ci-6 haloalkyl. In an embodiment, each R7is independently selected from the group consisting of halogen, Ci-6 alkoxyl, and Ci-6 haloalkyl.

[0089] In an embodiment, R7is -OH. In an embodiment, R7is halogen. In an embodiment, R7is -Cl. In an embodiment, R7is -F. In an embodiment, R7is -Br. In an embodiment, R7is -I. In an embodiment, R7is Ci-6 alkyl. In an embodiment, R7is -CH3. In an embodiment, R7is -Et. In an embodiment, R7is Ci-6 alkoxyl (e.g., -OCH3). In an embodiment, R7is -OCH3. In an embodiment, R7is Ci-6 haloalkyl (e.g., -CF3). In an embodiment, R7is -CF3. In an embodiment, R7is Ci-6 haloalkoxyl.

[0090] Target Ligand

[0091] As generally described herein, R8is wherein L2is as described herein, and the Target Ligand comprises a moiety capable of binding to a target protein (e.g., a Target Ligand as described herein). As generally described herein, L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene-*, -C(0)-Co-4 heteroalkylene-*, and -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is absent. In an embodiment, L2is a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene-*, -C(0)-Co-4 heteroalkylene-*, and -C(0)-Co-4 alkylene- O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I).

[0092] In an embodiment, L2is selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene-*, -C(0)-Co-4 heteroalkylene-*, and -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R13, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is selected from the group of -C(0)-Co-4 alkylene-*, -C(0)-Co-4 heteroalkylene- *, and -C(0)-Co-4 alkylene-O-*, wherein each heteroalkylene and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is selected from -C(0)-Co-4 heteroalkylene-* and -C(0)-Co-4 alkylene-O-*, wherein each heteroalkylene and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is -C(0)-Co-4 alkylene-O-*, wherein the alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I).

[0093] In an embodiment, L2is alkyl, optionally substituted with one or more R13. In an embodiment, L2is methylene, optionally substituted with one or more R13. In an embodiment, L2is ethylene, optionally substituted with one or more R13. In an embodiment, L2is propylene, optionally substituted with one or more R13. In an embodiment, L2is butylene, optionally substituted with one or more R15. In an embodiment, L2is heteroalkyl, optionally substituted with one or more R15.

[0094] In an embodiment, L2is -C(0)-Co-4 alkylene-*, wherein the alkylene is optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is -C(O)-*, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). Tn an embodiment, L2is -C(O)-Ci-4 alkylene-*, wherein the alkylene is optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is -C(O)-Ci alkylene-*, wherein the alkylene is optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is -C(O)-C2 alkylene-*, wherein the alkylene is optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is -C(O)-C3 alkylene-*, wherein the alkylene is optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is -C(O)-C4 alkylene-*, wherein the alkylene is optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I).

[0095] In an embodiment, L2is -C(0)-Co-4 heteroalkylene-*, wherein the heteroalkylene is optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is -C(O)-Ci-4 heteroalkylene-*, wherein the heteroalkylene is optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is -C(O)- Ci heteroalkylene-*, wherein the heteroalkylene is optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is -C(O)-C2 heteroalkylene-*, wherein the heteroalkylene is optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is -C(O)-Cs heteroalkylene-*, wherein the heteroalkylene is optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is -C(O)-C4 heteroalkylene-*, wherein the heteroalkylene is optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I).

[0096] In an embodiment, L2is -C(0)-Co-4 alkylene-O-*, wherein the alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is -C(O)-O-*, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is -C(O)-Ci-4 alkylene-O-*, wherein the alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is -C(O)-Ci alkylene-O-*, wherein the alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is -C(O)-C(R15a)(R15b)-O-*, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is -C(0)-CH2-0-*, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I).

[0097] In an embodiment, L2is -C(O)-C2 alkylene-O-*, wherein the alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is -C(O)-Cs alkylene-O-*, wherein the alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). In an embodiment, L2is -C(O)-C4 alkylene-O-*, wherein the alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I).

[0098] As generally described herein, each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3.8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring.

[0099] In some embodiments, each R9is independently selected from the group consisting of - OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl. In some embodiments, R9is -OH. In some embodiments, R9is halogen. In some embodiments, R9is -Cl. In some embodiments, R9is -F. In some embodiments, R9is -Br. In some embodiments, R9is -I. In some embodiments, R9is Ci-6 alkyl (e.g., methyl, ethyl, propyl). In some embodiments, R9is - CH3. In some embodiments, R9is -Me. In some embodiments, R9is -Et. In some embodiments, R9is propyl. In some embodiments, R9is Ci-6 alkoxyl. In some embodiments, R9is -OMe. In some embodiments, R9is -OEt. In some embodiments, R9is Ci-6 haloalkyl. In some embodiments, R9is -CF3. In some embodiments, R9is -CFH2. In some embodiments, R9is - CF2H. In some embodiments, R9is Ci-6 haloalkoxyl. In some embodiments, R9is -OCF3. In some embodiments, two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo. In some embodiments, two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl. In some embodiments, two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-6 cycloalkyl. In some embodiments, two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3 cycloalkyl. In some embodiments, two R9on the same carbon atom together with the same carbon atom to which they are attached form a C4 cycloalkyl. In some embodiments, two R9on the same carbon atom together with the same carbon atom to which they are attached form a C5 cycloalkyl. In some embodiments, two R9on the same carbon atom together with the same carbon atom to which they are attached form a Ce cycloalkyl. In some embodiments, two R9on the same carbon atom together with the same carbon atom to which they are attached form a C7 cycloalkyl. In some embodiments, two R9on the same carbon atom together with the same carbon atom to which they are attached form a Cs cycloalkyl. In some embodiments, two R9on the same carbon atom together with the same carbon atom to which they are attached form an oxo.

[0100] In some embodiments, two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl. In some embodiments, two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-5 cycloalkyl. In some embodiments, two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3 cycloalkyl. In some embodiments, two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C4 cycloalkyl. In some embodiments, two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C5 cycloalkyl. In some embodiments, two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a G, cycloalkyl. In some embodiments, two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C7 cycloalkyl. In some embodiments, two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a Cs cycloalkyl. In some embodiments, two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring. As generally described herein, each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl. In some embodiments, each R10is independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, and C1-6 alkoxyl. In some embodiments, each R10is independently selected from the group consisting of hydrogen, -OH, and C1-6 alkyl. In some embodiments, each R10is independently selected from the group consisting of hydrogen and C1-6 alkyl.

[0101] In some embodiments, R10is hydrogen. In some embodiments, R10is -OH. In some embodiments, R10is halogen. In some embodiments, R10is -Cl. In some embodiments, R10is -F. In some embodiments, R10is -Br. In some embodiments, R10is -I. In some embodiments, R10is C1-6 alkyl. In some embodiments, R10is -CH3. In some embodiments, R10is -Me. In some embodiments, R10is -Et. In some embodiments, R10is propyl. In some embodiments, R10is C1-6 alkoxyl. In some embodiments, R10is -OMe. In some embodiments, R10is -OEt. In some embodiments, R10is C1-6 hydroxyalkyl. In some embodiments, R10is C1-6 haloalkyl. In some embodiments, R10is -CF3. In some embodiments, R10is -CFH2. In some embodiments, R10is - CF2H. In some embodiments, R10is C1-6 haloalkoxyl. In some embodiments, R10is -OCF3. In some embodiments, R10is C3-8 cycloalkyl. In some embodiments, R10is cyclopropyl. In some embodiments, R10is cyclobutyl. In some embodiments, R10is cyclopentyl. In some embodiments, R10is cyclohexyl.

[0102] As generally described herein, R11is selected from the group consisting of -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and Ci-6 haloalkoxyl. In some embodiments, R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, and Ci-6 haloalkyl. In some embodiments, R11is selected from the group consisting of -OH, halogen, and Ci-6 alkyl. In some embodiments, R11is selected from the group consisting of -OH and Ci-6 alkyl.

[0103] In some embodiments, R11is -OH. In some embodiments, R11is halogen. In some embodiments, R11is -Cl. In some embodiments, R11is -F. In some embodiments, R11is -Br. In some embodiments, R11is -I. In some embodiments, R11is Ci-6 alkyl. In some embodiments, R11is -CH3. In some embodiments, R11is -Me. In some embodiments, R11is -Et. In some embodiments, R11is propyl. In some embodiments, R11is Ci-6 alkoxyl. In some embodiments, R11is -OMe. In some embodiments, R11is -OEt. In some embodiments, R11is Ci-6 haloalkyl. In some embodiments, R11is -CF3. In some embodiments, R11is -CFH2. In some embodiments, R11is -CF2H. In some embodiments, R11is Ci-6 haloalkoxyl. In some embodiments, R11is -OCF3.

[0104] As generally described herein, R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, and C1-6 haloalkyl. In some embodiments, R12is hydrogen, halogen, or Ci-6 alkyl. In some embodiments, R12is hydrogen or C1-6 alkyl.

[0105] In some embodiments, R12is hydrogen. In some embodiments, R12is halogen. In some embodiments, R12is -Cl. In some embodiments, R12is -F. In some embodiments, R12is -Br. In some embodiments, R12is -I. In some embodiments, R12is Ci-6 alkyl. In some embodiments, R12is -CH3. In some embodiments, R12is -Me. In some embodiments, R12is -Et. In some embodiments, R12is propyl. In some embodiments, R12is Ci-6 alkoxyl. In some embodiments, R12is -OMe. In some embodiments, R12is -OEt. In some embodiments, R12is Ci-6 hydroxyalkyl. In some embodiments, R12is Ci-6 haloalkyl. In some embodiments, R12is -CF3. In some embodiments, R12is -CFH2. In some embodiments, R12is -CF2H.

[0106] As generally described herein, each R13is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl. In some embodiments, each R13is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl.

[0107] In some embodiments, R13is hydrogen. In some embodiments, R13is -OH. In some embodiments, R13is halogen. In some embodiments, R13is -Cl. In some embodiments, R13is -F. In some embodiments, R13is -Br. In some embodiments, R13is -I. In some embodiments, R13is Ci-6 alkyl. In some embodiments, R13is -CH3. In some embodiments, R13is -Me. In some embodiments, R13is -Et. In some embodiments, R13is propyl. In some embodiments, R13is Ci-6 alkoxyl. In some embodiments, R13is -OMe. In some embodiments, R13is -OEt. In some embodiments, R13is Ci-6 hydroxyalkyl. In some embodiments, R13is Ci-6 haloalkyl. In some embodiments, R13is -CF3. In some embodiments, R13is -CFH2. In some embodiments, R13is - CF2H. In some embodiments, R13is Ci-6 haloalkoxyl. In some embodiments, R13is -OCF3. In some embodiments, R13is C3-8 cycloalkyl.

[0108] As generally described herein, each R15is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl. In some embodiments, each R15is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl. In some embodiments, each R15is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, and Ci-6 haloalkyl. In some embodiments, each R13is independently selected from hydrogen, -OH, and Ci-6 alkyl. In some embodiments, each R15is independently selected from hydrogen and Ci-6 alkyl.

[0109] In some embodiments, R15is hydrogen. In some embodiments, R15is -OH. In some embodiments, R15is halogen. In some embodiments, R13is -Cl. In some embodiments, R15is -F. In some embodiments, R15is -Br. In some embodiments, R15is -I. In some embodiments, R15is Ci-6 alkyl (e.g., methyl, ethyl, propyl). In some embodiments, R15is -CH3. In some embodiments, R15is -Me. In some embodiments, R13is -Et. In some embodiments, R13is propyl. In some embodiments, R15is Ci-6 alkoxyl. In some embodiments, R15is -OMe. In some embodiments, R15is -OEt. In some embodiments, R15is Ci-6 hydroxyalkyl. In some embodiments, R15is C1-6 haloalkyl. In some embodiments, R15is -CF3. In some embodiments, R15is -CFH2. In some embodiments, R15is -CF2H. In some embodiments, R15is Ci-6 haloalkoxyl. In some embodiments, R15is -OCF3. In some embodiments, R15is C3-8 cycloalkyl.

[0110] As generally described herein, R15aand R15bare independently selected from hydrogen, - OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3- s cycloalkyl. In some embodiments, R13aand R13bare independently selected from hydrogen, - OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl. In some embodiments, R15aand R15bare independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, and Ci-6 haloalkyl. In some embodiments, R15aand R15bare independently selected from hydrogen, -OH, and Ci-6 alkyl. In some embodiments, R13aand R15bare independently selected from hydrogen and Ci-6 alkyl. In some embodiments, R13aand R13bare both hydrogen.

[0111] In some embodiments, R15ais hydrogen. In some embodiments, R15ais -OH. In some embodiments, R15ais halogen. In some embodiments, R15ais -Cl. In some embodiments, R15ais - F. In some embodiments, R15ais -Br. In some embodiments, R15ais -I. In some embodiments, R15ais Ci-6 alkyl (e.g., methyl, ethyl, propyl). In some embodiments, R13ais -CH3. In some embodiments, R15ais -Me. In some embodiments, R15ais -Et. In some embodiments, R15ais propyl. In some embodiments, R15ais Ci-6 alkoxyl. In some embodiments, R15ais -OMe. In some embodiments, R15ais -OEt. In some embodiments, R15ais Ci-6 hydroxyalkyl. In some embodiments, R15ais Ci-6 haloalkyl. In some embodiments, R15ais -CF3. In some embodiments, R1?ais -CFH2. In some embodiments, R15ais -CF2H. In some embodiments, R15ais C1-6 haloalkoxyl. In some embodiments, R15ais -OCF3. In some embodiments, R15ais C3-8 cycloalkyl.

[0112] In some embodiments, R15bis hydrogen. In some embodiments, R15bis -OH. In some embodiments, R13bis halogen. In some embodiments, R1?bis -Cl. In some embodiments, R15bis - F. In some embodiments, R15bis -Br. In some embodiments, R15bis -I. In some embodiments, R15bis Ci-6 alkyl (e.g., methyl, ethyl, propyl). In some embodiments, R15bis -CH3. In some embodiments, R15bis -Me. In some embodiments, R15bis -Et. In some embodiments, R13bis propyl. In some embodiments, R15bis C1-6 alkoxyl. In some embodiments, R15bis -OMe. In some embodiments, R13bis -OEt. In some embodiments, R15bis C1-6 hydroxyalkyl. In some embodiments, R15bis Ci-6 haloalkyl. In some embodiments, R15bis -CF3. In some embodiments, R15bis -CFH2. In some embodiments, R15bis -CF2H. In some embodiments, R13bis C1-6 haloalkoxyl. In some embodiments, R1?bis -OCF3. In some embodiments, R1?bis C3-8 cycloalkyl.

[0113] As generally described herein, RBis hydrogen or C1-6 alkyl. In some embodiments, RBis hydrogen. In some embodiments, RBis Ci-6 alkyl. In some embodiments, RBis C1.3 alkyl. In some embodiments, RBis -CH3. In some embodiments, RBis -Et. In some embodiments, RBis propyl. In some embodiments, RBis butyl.

[0114] As generally described herein, m is 0, 1, or 2. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 0 or 1.

[0115] As generally described herein, n is 0, 1, or 2. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 0 or 1.

[0116] As generally described herein, o is 0, 1, or 2. In some embodiments, o is 0. In some embodiments, 0 is 1. In some embodiments, o is 2. In some embodiments, 0 is 0 or 1.

[0117] As generally described herein, p is 0, 1, 2, 3, or 4. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, p is 3. In some embodiments, p is 4. In some embodiments, p is 0, 1, 2, or 3. In some embodiments, p is 0, 1, or 2. In some embodiments, p is 1, 2, 3, or 4. In some embodiments, p is 1, 2, or 3.

[0118] As generally described herein, q is selected from 0, 1, 2, 3, or 4. In some embodiments, q is 0, 1, 2, or 3. In some embodiments, q is 0, 1, or 2. In some embodiments, q is 0 or 1. 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 an embodiment, X is O. In an embodiment, X is S. In an embodiment, R2ais hydrogen. In an embodiment, R2ais methyl. In an embodiment, R2bis hydrogen. In an embodiment, R2bis methyl. In an embodiment, each of R3aand R3bis independently hydrogen or Ci-6 alkyl. In an embodiment, one of R3aand R3bis hydrogen. In an embodiment, each of R3aand R3bare hydrogen. In an embodiment, L2is absent. In an embodiment, L2is a linker. In an embodiment,

[0119] L2is a linker selected from the group of , wherein * denotes where L2connects to the Target Ligand. In an embodiment, R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl. In an embodiment, R8aand R8b, together with the atoms to which they are attached, form an oxo group. In an embodiment, each of R8aand R8bis independently hydrogen or C1-6 alkyl. In an embodiment, R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, C1-6 alkyl, and Ci-6 haloalkyl. In an embodiment, o is 1 or 2. In an embodiment, o is 0.

[0120] In an embodiment, R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, C1-6 alkyl, and C1-6 haloalkyl. In an embodiment, R4and R5are each independently selected from the group consisting of hydrogen, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl. In an embodiment, each of R4and R5is independently hydrogen or Ci-6 alkyl. In an embodiment, m is 1 or 2. In an embodiment, m is 0. In an embodiment, n is 1 or 2. In an embodiment, n is 0. In an embodiment, n is 1. In an embodiment, n is 2. In an embodiment, Ring A is 6- to 10-membered aryl (e.g., phenyl). In an embodiment, Ring A is 5- to 10-membered heteroaryl (e.g., pyridyl). In an embodiment, p is 0, 1, 2, or 3. In an embodiment, L2is absent. In an embodiment, L2is a linker (e.g., a linker described herein).

[0121] In an embodiment, the Target Ligand is a kinase inhibitor, bromodomain inhibitor, or phosphodiesterase inhibitor. In an embodiment, the Target Ligand is capable of binding to CDK4, CDK6, BRD4, PDE5, BCR-ABL, c-ABL, AR, AR-V7, BTK, LRRK2, or SMARCA2. In an embodiment, the Target Ligand is selected from ribociclib, dasatinib, palbociclib, sildenafil, HG- 10-102-01, JQ1, ibrutinib, or a derivative thereof.

[0122] In an embodiment, X is O. In an embodiment, each of R3aand R3bis independently hydrogen or Ci-6 alkyl. In an embodiment, each of R6aand R6bis independently hydrogen or Ci-6 alkyl. In an embodiment, R4and R5are each independently selected from the group consisting of hydrogen, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl. In an embodiment, each of R4and R5is independently hydrogen or Ci-6 alkyl. In an embodiment, m is 1 or 2. In an embodiment, n is 1 or 2. In an embodiment, Ring A is 6- to 10-membered aryl (e.g., phenyl). In an embodiment, Ring A is 5- to 10-membered heteroaryl (e.g., pyridyl). In an embodiment, p is 0, 1, 2, or 3. In an embodiment, L2is absent. In an embodiment, L2is a linker (e.g., a linker described herein). In an embodiment, the Target Ligand is a kinase inhibitor, bromodomain inhibitor, or phosphodiesterase inhibitor. In an embodiment, the Target Ligand is capable of binding to CDK4, CDK6, BRIM, PDE5, BCR-ABL, c-ABL, AR, AR-V7, BTK, LRRK2, or SMARCA2. In an embodiment, the Target Ligand is selected from ribociclib, dasatinib, palbociclib, sildenafil, HG-10-102-01, JQ1, ibrutinib, or a derivative thereof.

[0123] Linkers

[0124] In an embodiment, the molecule glue degrader compound comprises a linker, termed “linker”, “L” or “L2herein. In an embodiment, the linker, L, or L2is absent. In an embodiment, the linker or L is L2. In an embodiment, L2is absent. In an embodiment, L2is a linker selected from the group of alkyl, heteroalkyl, -(Ci-4 alkyl-NR)-, C1-5 cycloalkyl, -(C1-5 cycloalkyl)-NR-, wherein R is hydrogen or C 1-6 alkyl.

[0125] In an embodiment of Formula (II) and related subgenera, R1and R2together with the atoms to which they are attached form a ring, referred to hereinafter as “Ring B”, wherein Ring B is further substituted with R8, and 0-4 occurrences of R9. In an embodiment, Ring B is a heteroaryl or heterocycloalkyl ring. In an embodiment, Ring B is a 5- to 10-membered heteroaryl or a 3- to 12-membered heterocycloalkyl ring.

[0126] Target Ligands

[0127] As generally described herein, the Target Ligand comprises a moiety capable of binding to a target protein.

[0128] In an embodiment, the Target Ligand is a kinase inhibitor, bromodomain inhibitor, or phosphodiesterase inhibitor. In an embodiment, the Target Ligand is capable of binding to CDK4, CDK6, BRIM, PDE5, BCR-ABL, c-ABL, AR, AR-V7, BTK, LRRK2, or SMARCA2. In an embodiment, the Target Ligand is selected from ribociclib, dasatinib, palbociclib, sildenafil, HG-10-102-01, JQ1, ibrutinib, or a derivative thereof. In an embodiment, the Target Ligand wherein R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; R13is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; and q is 0, 1, 2, 3, or 4.

[0129] In an embodiment, the Target Ligand is selected from the group

[0130] In an embodiment, the Target Ligand

[0131] In an embodiment, the Target Ligand is an aryl or heteroaryl ring. In an embodiment, the Target Ligand is an aryl ring (e.g., phenyl). In an embodiment, the Target Ligand is a heteroaryl ring

[0132] (e.g., pyridyl). In an embodiment, the Target Ligand is selected from

[0133] In an embodiment, the molecular glue degrader compounds have the structure of Formula

[0134] (ILc): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: X is O or S; Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10-membered heteroaryl, a 3- to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl; L2is a linker substituted with 0-4 occurrences of R9; Target Ligand comprises a moiety capable of binding to a target protein; R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; R3aand R3bare each independently selected from the group consisting of hydrogen, - OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, Ci-6 haloalkoxyl, and C3- s cycloalkyl; or R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci- 6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0135] In an embodiment, the molecular glue degrader compounds have the structure of Formula (II-d): acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: X is O or S; Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10-membered heteroaryl, a 3- to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl, optionally substituted with one or more R7; Target Ligand comprises a moiety capable of binding to a target protein; R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, C1-6 alkyl, and C1-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0136] In an embodiment, the molecular glue degrader compounds have the structure of Formula

[0137] (II-e): acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: X is O or S; Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10-membered heteroaryl, a 3- to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl, optionally substituted with one or more R7; Target Ligand comprises a moiety capable of binding to a target protein; R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, C1-6 alkyl, and C1-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0138] In an embodiment, the molecular glue degrader compounds have the structure of Formula

[0139] (ILf): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: X is O or S; Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3 - to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl, optionally substituted with one or more R7; R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R10is independently selected from the group consisting of hydrogen, - OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3- 8 cycloalkyl; R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; R13aand R13bare each independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; RBis hydrogen or Ci-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, 4, or 5; and q is 0, 1, 2, 3, or 4.

[0140] In an embodiment, the molecular glue degrader compounds have the structure of Formula

[0141] (II-g): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: X is O or S; R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of- OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; R11is selected from the group consisting of -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl; R12is selected from the group consisting of hydrogen, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, and C1-6 haloalkyl; R13is selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; R15aand R15bare each independently selected from hydrogen, - OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, Ci-6 haloalkoxyl, and C3- 8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, 4, or 5; and q is 0, 1, 2, 3, or 4.

[0142] In an embodiment, the molecular glue degrader compounds have the structure of Formula

[0143] (II-h): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl; each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; R13aand R15bare each independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; n is 0, 1, or 2; p is 0, 1, 2, 3, 4, or 5; and q is 0, 1, 2, 3, or 4.

[0144] In an embodiment, the molecular glue degrader compounds have the structure of Formula (ILi): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein X1and X2are each independently O or S; Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10-membered heteroaryl, a 3- to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl; Target Ligand comprises a moiety capable of binding to a target protein; R2aand R2bare each independently hydrogen, C1-6 alkyl, and C3-8 cycloalkyl; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R3are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of- OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; 0 is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0145] In an embodiment, the molecular glue degrader compounds have the structure of Formula pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein X is O or S; Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10-membered heteroaryl, a 3- to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl, optionally substituted with one or more R7; L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene-*, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (1); Target Ligand comprises a moiety capable of binding to a target protein; R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, C1-6 alkyl, and C1-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, - OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, Ci-6 haloalkoxyl, and C3- 8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; each R15is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0146] In an embodiment, the molecular glue degrader compounds have the structure of Formula (II-k): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein X1and X2are each independently O or S; Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10-membered heteroaryl, a 3- to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl; Target Ligand comprises a moiety capable of binding to a target protein; R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, C1-6 alkyl, and C1-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of- OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl; R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; o is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0147] In an embodiment, the molecular glue degrader compounds have the structure of Formula (II-l): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein X1and X2are each independently O or S; Target Ligand comprises a moiety capable of binding to a target protein; R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, C1-6 alkyl, and C1-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of- OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; o is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0148] In an embodiment, the molecular glue degrader compounds have the structure of Formula (ILm): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein X1and X2are each independently O or S; Target Ligand comprises a moiety capable of binding to a target protein; R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, C1-6 alkyl, and C1-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of- OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl; R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; o is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0149] In an embodiment, the molecular glue degrader compound have the structure of Formula (II-n): acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl; each R7and R11is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10and R13is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; o is 0, 1, or 2; p is 0, 1, 2, 3, 4, or 5; and q is 0, 1, 2, 3, or 4.

[0150] In an embodiment, the molecular glue degrader compound have the structure of Formula

[0151] (II-o): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, C1-6 alkyl, and C1-6 haloalkyl; each R7and R11is independently selected from the group consisting of -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and Ci-6 haloalkoxyl; R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or R8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10and R13is independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, C1-6 hydroxyalkyl, and Ci-6 haloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; o is 0, 1, or 2; p is 0, 1, 2, 3, 4, or 5; and q is 0, 1, 2, 3, or

[0152] 4.

[0153] In an embodiment, the molecular glue degrader compounds have the structure of Formula (II-p): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, C1-6 alkyl, and C1-6 haloalkyl; each R7and R11is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and Ci-6 haloalkoxyl; R7ais selected from the group consisting of hydrogen, Ci-6 alkyl, or C3-8 cycloalkyl; R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10and R13is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; o is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0154] In an embodiment, the molecular glue degrader compounds have the structure of Formula (ILq): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein R2a and R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; R4and R?are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, C1-6 alkyl, and C1-6 haloalkyl; each R7and R11is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl; R7ais selected from the group consisting of hydrogen, Ci-6 alkyl, or C3-8 cycloalkyl; R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or R8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10and R13is independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, C1-6 hydroxyalkyl, and Ci-6 haloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; o is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0155] In an embodiment, the molecular glue degrader compounds have the structure of Formula

[0156] (II-r): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: X is O or S; Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10-membered heteroaryl, a 3- to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl, optionally substituted with one or more R7; L1is a linker selected from the group of alkyl, heteroalkyl, C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R1?, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I); R2is selected from the group consisting of hydrogen and Ci-6 alkyl; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; R7is selected from the group consisting of -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci-6 haloalkyl, and C1-6 haloalkoxyl; R10is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0157] In an embodiment, the molecular glue degrader compounds have the structure of Formula

[0158] (Ill-a): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: X is O or S; Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7; L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene-*, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; R4and R5are each independently selected from the group consisting of hydrogen, - OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the nonadj acent carbon atoms to which they are attached form a bridging ring; R11is selected from the group consisting of -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl; R12is selected from the group consisting of hydrogen, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, and C1-6 haloalkyl; R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3- cycloalkyl; each R15is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; RBis hydrogen or Ci-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0159] In an embodiment, the molecular glue degrader compounds have the structure of Formula (Ill-b): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: X is O or S; Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of- OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; R11is selected from the group consisting of -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl; R12is selected from the group consisting of hydrogen, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, and C1-6 haloalkyl; R13is selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; R15aand R15bare each independently selected from hydrogen, - OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, Ci-6 haloalkoxyl, and C3- 8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0160] In an embodiment, the molecular glue degrader compounds have the structure of Formula (III-c): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: X is O or S; Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of- OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; R11is selected from the group consisting of -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0161] In an embodiment, the molecular glue degrader compounds have the structure of Formula (Ill-d): (Ill-d), or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: X is O or S; L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene-*, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); Target Ligand comprises a moiety capable of binding to a target protein; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of- OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R13is independently selected from hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; RBis hydrogen or C1-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0162] In an embodiment, the molecular glue degrader compounds have the structure of Formula (Hl-e): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: X is O or S; L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene-*, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; R4and R are each independently selected from the group consisting of hydrogen, -OH, halogen, - CN, Ci-6 alkyl, and Ci-6 haloalkyl; R6aand R611are each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; R7are each independently selected from the group consisting of- OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; R11is selected from the group consisting of- OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl; R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, C1-6 hydroxyalkyl, and Ci-6 haloalkyl; R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; each R15is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; RBis hydrogen or Ci-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0163] In an embodiment, the molecular glue degrader compounds have the structure of Formula (III-f): or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: X is O or S; L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene-*, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R1?, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, - CN, Ci-6 alkyl, and Ci-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; R7are each independently selected from the group consisting of- OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; R11is selected from the group consisting of- OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl; R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, C1-6 hydroxyalkyl, and Ci-6 haloalkyl; R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; R15aand R15bare each independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; RBis hydrogen or Ci-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0164] In an embodiment, the molecular glue degrader compounds have the structure of Formula (III-g): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10-membered heteroaryl, a 3- to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl, optionally substituted with one or more R7; L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene-*, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; R4and R5are each independently selected from the group consisting of hydrogen, - OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl; R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, C1-6 haloalkyl, and Ci-6 haloalkoxyl; R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; each R15is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; RBis hydrogen or Ci-6 alkyl; n is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0165] In an embodiment, the molecular glue degrader compound of Formula (I) has the structure having a structure of Formula (Ill-h): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein Ring B is a 5- to 10-membered heteroaryl or a 3- to 12-membered heterocycloalkyl, and each of the Ring A, L2, R4, R5, R6a, R6b, R7, R9, m, p, and q are as defined for Formula (II).

[0166] In an embodiment, the molecular glue degrader compound is a compound selected from Table 1, or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof.

[0167] Table 1: Exemplary molecular glue degrader compounds In some embodiments, the molecular glue degrader compound is Compound 132 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. In some embodiments, the molecular glue degrader compound is Compound 133 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. In some embodiments, the molecular glue degrader compound is Compound 289 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. In some embodiments, the molecular glue degrader compound is Compound 290 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. In some embodiments, the molecular glue degrader compound is Compound 291 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. In some embodiments, the molecular glue degrader compound is Compound 292 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. In some embodiments, the molecular glue degrader compound is Compound 293 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. In some embodiments, the molecular glue degrader compound is Compound 294 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. Target Proteins

[0168] In one aspect, the disclosure provides a molecular glue degrader compound or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which recruit a targeted protein, such as a protein kinase, a phosphodiesterase, or a bromodomain-containing protein to a RING E3 ubiquitin ligase for degradation.

[0169] In an embodiment, the target protein is selected from a tyrosine kinase, a serine / threonine kinase, a bromodomain-containing protein, an epigenetic protein, and a misfolded protein. The target protein may be selected from AR, BCL-2 / BCL, BCL-XL, BCR-ABL, BRD2, BRD3, BRD4, BRD9, BRDT, BTK, BUB1, BUB1B, c-ABL, CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11B, CDK12, CDK13, CDK14, CDK15, CDK16, CDK17, CDK18, CDK19, CDK20, CHEK1, CKS1B, CKS2, CSNK1A1, CSNK1E, CTNNB1, DSTYK, EEF2K, estrogen receptor (ER), ETNK1, FASTKD5, HRAS, ITPKB, KRAS, KRAS4A, KRAS4B, KRAS G12A, KRAS G12C, KRAS G12D, KRAS G12S, KRAS G12V, KRAS G13D, LRKK2, MAPKAPK2 (MK2), MARK2, MAP3K2, MELK, MYC, MYCN, NEK6, NRAS, PANK2, PANK3, PDE5, PHKA1 , PHKA2, PKN2, PLK1, PTK6, RI0K2, SKP2, SMARCA2, SMARCA4, STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6, TK1, TTK, and UCK2. In an embodiment, the target protein is selected from a protein listed in Table 3 below.

[0170] In an embodiment, the target protein is selected from AR-V7, BCL-2 / BCL, BCR-ABL, BRD4, BTK, BUB1, BUB1B, c-ABL, CDK4, CDK11B, CHEK1, CKS1B, CKS2, CSNK1A1, CSNK1E, DSTYK, EEF2K, ETNK1, FASTKD5, ITPKB, KRAS G12D, LRKK2, MARK2, MAP3K2, MELK, NEK6, PANK2, PANK3, PDE5, PHKA1, PHKA2, PKN2, PLK1, RI0K2, SKP2, SMARCA2, TK1, TTK, and UCK2.

[0171] In an embodiment, the target protein is AR. In an embodiment, the target protein is AR- V7. In an embodiment, the target protein is Bcl-2 / Bcl. In an embodiment, the target protein is BCR-ABL. In an embodiment, the target protein is BRD2. In an embodiment, the target protein is BRD2. In an embodiment, the target protein is BRD3. In an embodiment, the target protein is BRD2. In an embodiment, the target protein is BRD4. In an embodiment, the target protein is BRIM. In an embodiment, the target protein is BRD9. In an embodiment, the target protein is BRDT. In an embodiment, the target protein is BTK. In an embodiment, the target protein is BUB1. In an embodiment, the target protein is BUB IB. In an embodiment, the target protein is BRD2. In an embodiment, the target protein is BUB1. In an embodiment, the target protein is BRD2. In an embodiment, the target protein is CKD1. In an embodiment, the target protein is BRD2. In an embodiment, the target protein is CKD2. In an embodiment, the target protein is BRD2. In an embodiment, the target protein is CKD3. In an embodiment, the target protein is c- ABL. In an embodiment, the target protein is CDK4. In an embodiment, the target protein is c- ABL. In an embodiment, the target protein is CDK5. In an embodiment, the target protein is c- ABL. In an embodiment, the target protein is CDK6. In an embodiment, the target protein is c- ABL. In an embodiment, the target protein is CDK7. In an embodiment, the target protein is CDK8. In an embodiment, the target protein is CDK8. In an embodiment, the target protein is c- ABL. In an embodiment, the target protein is CDK9. In an embodiment, the target protein is c- ABL. In an embodiment, the target protein is CDK10. In an embodiment, the target protein is CDK9. In an embodiment, the target protein is CDK1 IB. In an embodiment, the target protein is c-ABL. In an embodiment, the target protein is CDK12. In an embodiment, the target protein is c-ABL. In an embodiment, the target protein is CDK13. In an embodiment, the target protein is c-ABL. In an embodiment, the target protein is CDK14. In an embodiment, the target protein is c-ABL. In an embodiment, the target protein is CDK15. In an embodiment, the target protein is c-ABL. In an embodiment, the target protein is CDK16. In an embodiment, the target protein is c-ABL. In an embodiment, the target protein is CDK17. In an embodiment, the target protein is c-ABL. In an embodiment, the target protein is CDK18. In an embodiment, the target protein is c-ABL. In an embodiment, the target protein is CDK19. In an embodiment, the target protein is c-ABL. In an embodiment, the target protein is CDK20. In an embodiment, the target protein is c-ABL. In an embodiment, the target protein is CHEK1. In an embodiment, the target protein is CHEK1. In an embodiment, the target protein is CKS1B. In an embodiment, the target protein is c-ABL. In an embodiment, the target protein is CKS2. In an embodiment, the target protein is CKS2. In an embodiment, the target protein is CSNK1A1. In an embodiment, the target protein is CKS2. In an embodiment, the target protein is CSNK1E. In an embodiment, the target protein is CKS2. In an embodiment, the target protein is CTNNB 1. In an embodiment, the target protein is CSNK1E. In an embodiment, the target protein is DSTYK. In an embodiment, the target protein is EEF2K. In an embodiment, the target protein is estrogen receptor (ER). In an embodiment, the target protein is ETNK1. In an embodiment, the target protein is FASTKD5. In an embodiment, the target protein is HRAS. In an embodiment, the target protein is ITPKB. In an embodiment, the target protein is KRAS. In an embodiment, the target protein is KRAS4A. In an embodiment, the target protein is KRAS4B. In an embodiment, the target protein is KRAS4A. In an embodiment, the target protein is KRAS G12A. In an embodiment, the target protein is KRAS G12B. In an embodiment, the target protein is KRAS G12C. In an embodiment, the target protein is KRAS G12D. In an embodiment, the target protein is KRAS G12S. In an embodiment, the target protein is KRAS G12V. In an embodiment, the target protein is KRAS G13D. In an embodiment, the target protein is LRRK2. In an embodiment, the target protein is MAPKAPK2. In an embodiment, the target protein is MARK2. In an embodiment, the target protein is MAP3K2. In an embodiment, the target protein is MELK. In an embodiment, the target protein is MYC. In an embodiment, the target protein is MYCN. In an embodiment, the target protein is NEK6. In an embodiment, the target protein is NRAS. In an embodiment, the target protein is PANK2. In an embodiment, the target protein is PANK3. In an embodiment, the target protein is PBRM1. In an embodiment, the target protein is PDE5. In an embodiment, the target protein is PHKA1 . In an embodiment, the target protein is PHKA2. In an embodiment, the target protein is PKN2. In an embodiment, the target protein is PLK1. In an embodiment, the target protein is PTK6. In an embodiment, the target protein is RI0K2. In an embodiment, the target protein is RIPK2. In an embodiment, the target protein is SKP2. In an embodiment, the target protein is SMARCA2. In an embodiment, the target protein is SMARCA4. In an embodiment, the target protein is STAT1. In an embodiment, the target protein is STAT2. In an embodiment, the target protein is STAT3. In an embodiment, the target protein is STAT4. In an embodiment, the target protein is STAT5A. In an embodiment, the target protein is STAT5B. In an embodiment, the target protein is STAT6. In an embodiment, the target protein is tau. In an embodiment, the target protein is TBK1. In an embodiment, the target protein is TK1. In an embodiment, the target protein is TTK. In an embodiment, the target protein is UCK2. In an embodiment, the target protein is WDR5. In an embodiment, the target protein is WEE1.

[0172] Definitions

[0173] One embodiment is a compound of any of the formulae described herein, e.g. a compound of Formula (I) and subformula thereof, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, that modulates, e.g., decreases the amount of a targeted protein or protein of interest, e.g., one or more proteins from Table 3.

[0174] Another embodiment is a Formula (I) and subformula thereof, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, that degrades a targeted protein through the ubiquitin-proteasome pathway (UPP).

[0175] The formation of a viable ternary complex among the target protein, the molecular glue degrader compound, and the RING E3 ubiquitin ligase is enabled by the use of targeted molecular glue degraders, relying on two key components, the “Target Ligand” and the “RING E3 Ligase Binder, and, optionally, the joining segment, termed the “Bridge.” In an embodiment, the molecular glue degrader may act as a monovalent degrader, binding to a target protein that then ultimately binds to a RING E3 ubiquitin ligase to facilitate ubiquitination of the target protein and degradation.

[0176] The term “a therapeutically effective amount” of a compound described herein refers to an amount of the compound described herein that will elicit the biological or medical response of a subject, for example, reduction or inhibition of an enzyme or a protein activity, or ameliorate symptoms, alleviate conditions, slow or delay disease progression, or prevent a disease, etc. In one embodiment, the term “a therapeutically effective amount” refers to the amount of the compound described herein that, when administered to a subject, is effective to (1) at least partially alleviate, prevent and / or ameliorate a condition, or a disorder or a disease (i) mediated by a target protein, (ii) associated with activity of a target protein, or (iii) characterized by activity (normal or abnormal) of a target protein; or (2) reduce or inhibit the activity of a target protein; or (3) reduce or inhibit the expression of a target protein. These effects may be achieved for example by reducing the amount of a target protein by degrading of the target protein. In one embodiment, the term “a therapeutically effective amount” refers to the amount of the compound described herein that, when administered to a cell, or a tissue, or a non-cellular biological material, or a medium, is effective to at least partially reduce or inhibit the activity of target protein; or at least partially reduce or inhibit the expression of a target protein, for example by degrading a target protein.

[0177] As used herein, the term cancer refers to a neoplastic disease and includes for instance solid tumors, such as, e.g. sarcomas or carcinomas or blood cancer, such as, e.g. leukemia or myeloma, or cancers of lymphatic system such as lymphoma, or mixed types thereof.

[0178] As used herein, the terms “degrades”, “degrading”, or “degradation” refers to the partial or full breakdown of a target protein by the cellular proteasome system to an extent that reduces or eliminates the biological activity (especially aberrant activity) of target protein. Degradation may be achieved through mediation of a RING E3 ligase, in particular, E3 -ligase complexes comprising the protein RNF126. As used herein, the term “modulation of target protein activity” or “modulating target activity” means the alteration of, especially reduction, suppression or elimination, of target protein’s activity. This may be achieved by degrading the target protein in vivo or in vitro. The amount of target protein degraded can be measured by comparing the amount of target protein remaining after treatment with a compound described herein as compared to the initial amount or level of target protein present as measured prior to treatment with a compound described herein. In an embodiment, at least about 30% of the target protein is degraded compared to initial levels. In an embodiment, at least about 40% of the target protein is degraded compared to initial levels. In an embodiment, at least about 50% of the target protein is degraded compared to initial levels. In an embodiment, at least about 60% of the target protein is degraded compared to initial levels. In an embodiment, at least about 70% of the target protein is degraded compared to initial levels. In an embodiment, at least about 80% of the target protein is degraded compared to initial levels. In an embodiment, at least about 90% of the target protein is degraded compared to initial levels. In an embodiment, at least about 95% of the target protein is degraded compared to initial levels. In an embodiment, over 95% of the target protein is degraded compared to initial levels. In an embodiment, at least about 99% of the target protein is degraded compared to initial levels.

[0179] In an embodiment, the target protein is degraded in an amount of from about 30% to about 99% compared to initial levels. In an embodiment, the target protein is degraded in an amount of from about 40% to about 99% compared to initial levels. In an embodiment, the target protein is degraded in an amount of from about 50% to about 99% compared to initial levels. In an embodiment, the target protein is degraded in an amount of from about 60% to about 99% compared to initial levels. In an embodiment, the target protein is degraded in an amount of from about 70% to about 99% compared to initial levels. In an embodiment, the target protein is degraded in an amount of from about 80% to about 99% compared to initial levels. In an embodiment, the target protein is degraded in an amount of from about 90% to about 99% compared to initial levels. In an embodiment, the target protein is degraded in an amount of from about 95% to about 99% compared to initial levels. In an embodiment, the target protein is degraded in an amount of from about 90% to about 95% compared to initial levels.

[0180] As used herein, the term “selectivity for the target protein” means, for example, a compound described herein degrades the target protein in preference to, or to a greater extent than, another protein or proteins.

[0181] As used herein, the term “subject” refers to an animal. Typically, the animal is a mammal. A subject also refers to, for example, primates (e.g., humans, male or female), cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice, fish, birds, and the like. In an embodiment, the subject is a primate. In a preferred embodiment, the subject is a human.

[0182] As used herein, the terms “inhibit”, “inhibition”, or “inhibiting” refer to the reduction or suppression of a given condition, symptom, or disorder, or disease, or a significant decrease in the baseline activity of a biological activity or process.

[0183] As used herein, the terms “treat”, “treating”, or “treatment” of any disease or disorder refer in an embodiment, to ameliorating the disease or disorder (z.e., slowing or arresting or reducing the development of the disease or at least one of the clinical symptoms thereof). In an embodiment, “treat”, “treating”, or “treatment” refers to alleviating or ameliorating at least one physical parameter including those which may not be discernible by the patient.

[0184] As used herein, the term “preventing” refers to a reduction in the frequency of, or delay in the onset of, symptoms of the condition or disease.

[0185] As used herein, a subject is “in need of’ a treatment if such subject would benefit biologically, medically, or in quality of life from such treatment.

[0186] As used herein, the term “a,” “an,” “the” and similar terms used in the context of the disclosure (especially in the context of the claims) are to be construed to cover both the singular and plural unless otherwise indicated herein or clearly contradicted by the context.

[0187] The term “alkyl” refers to a radical of a straight-chain or branched saturated hydrocarbon group having from 1 to 6 carbon atoms (“Ci-6 alkyl”). In some embodiments, an alkyl group has 1 to 5 carbon atoms (“C1-5 alkyl”). In some embodiments, an alkyl group has 1 to 4 carbon atoms (“C1-4 alkyl”). In some embodiments, an alkyl group has 1 to 3 carbon atoms (“C1-3 alkyl”). In some embodiments, an alkyl group has 1 to 2 carbon atoms (“C1-2 alkyl”). In some embodiments, an alkyl group has 1 carbon atom (“Ci alkyl”). In some embodiments, an alkyl group has 2 to 6 carbon atoms (“C2-6 alkyl”). Examples of Ci-6 alkyl groups include methyl (Ci), ethyl (C2), propyl (C3) (e.g., n-propyl, isopropyl), butyl (C4) (e.g, n-butyl, ze / 7-butyl, sec-butyl, isobutyl), pentyl (C5) (e.g., / / -pentyl, 3-pentanyl, amyl, neopentyl, 3-methyl-2-butanyl, tertiary amyl), and hexyl (Ce) (e. , / 7-hexyl).

[0188] “Alkylene” refers to a divalent radical of an alkyl group, e.g, -CH2-, -CH2CH2-, and -CH2CH2CH2-.

[0189] “Heteroalkyl” refers to an alkyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, or sulfur within ( / .e., inserted between adjacent carbon atoms of) and / or placed at one or more terminal position(s) of the parent chain. In certain embodiments, a heteroalkyl group refers to a saturated group having from 1 to 10 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroCi-10 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 9 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroCi-9 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 8 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroCi-s alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 7 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroCi-7 alkyl”). Tn some embodiments, a heteroalkyl group is a saturated group having 1 to 6 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroCi-6 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 5 carbon atoms and 1 or 2 heteroatoms within the parent chain (“heteroCi 5 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 4 carbon atoms and lor 2 heteroatoms within the parent chain (“heteroCi-4 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 3 carbon atoms and 1 heteroatom within the parent chain (“heteroCi-3 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 2 carbon atoms and 1 heteroatom within the parent chain (“heteroCi-2 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 carbon atom and 1 heteroatom (“heteroCi alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 2 to 6 carbon atoms and 1 or 2 heteroatoms within the parent chain (“heteroC2-6 alkyl”). Unless otherwise specified, each instance of a heteroalkyl group is independently unsubstituted (an “unsubstituted heteroalkyl”) or substituted (a “substituted heteroalkyl”) with one or more substituents. In certain embodiments, the heteroalkyl group is an unsubstituted heteroCi-10 alkyl. In certain embodiments, the heteroalkyl group is a substituted heteroCi-10 alkyl.

[0190] “Heteroalkylene” refers to a divalent radical of a heteroalkyl group.

[0191] “Alkoxy” or “alkoxyl” refers to an -O-alkyl radical. In some embodiments, the alkoxy groups are methoxy, ethoxy, zz-propoxy, isopropoxy, zz-butoxy, / cvZ-butoxy, sfc-butoxy, zz- pentoxy, zz-hexoxy, and 1,2-dimethylbutoxy. In some embodiments, alkoxy groups are lower alkoxy, i.e., with between 1 and 6 carbon atoms. In some embodiments, alkoxy groups have between 1 and 4 carbon atoms.

[0192] As used herein, the term “aryl” refers to a stable, aromatic, mono- or bicyclic ring radical having the specified number of ring carbon atoms. Examples of aryl groups include, but are not limited to, phenyl, 1 -naphthyl, 2-naphthyl, and the like. The related term “aryl ring” likewise refers to a stable, aromatic, mono- or bicyclic ring having the specified number of ring carbon atoms.

[0193] As used herein, the term “heteroaryl” refers to a stable, aromatic, mono- or bicyclic ring radical having the specified number of ring atoms and comprising one or more heteroatoms individually selected from nitrogen, oxygen and sulfur. The heteroaryl radical may be bonded via a carbon atom or heteroatom. Examples of heteroaryl groups include, but are not limited to, furyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, pyrazinyl, pyridazinyl, pyrimidyl, pyridyl, quinolinyl, isoquinolinyl, indolyl, indazolyl, oxadiazolyl, benzothiazolyl, quinoxalinyl, and the like. The related term “heteroaryl ring” likewise refers to a stable, aromatic, mono- or bicyclic ring having the specified number of ring atoms and comprising one or more heteroatoms individually selected from nitrogen, oxygen and sulfur.

[0194] As used herein, the term “cycloalkyl” refers to a stable, saturated or unsaturated, or a mixture thereof, non-aromatic, mono- or bicyclic (fused, bridged, or spiro) ring radical having the specified number of ring carbon atoms. Examples of cycloalkyl groups include, but are not limited to, the cycloalkyl groups identified above, cyclobutenyl, cyclopentenyl, cyclohexenyl, and the like. In an embodiment, the specified number is C3-C12 carbons. The related term “cycloalkyl ring” likewise refers to a stable, saturated or unsaturated, non-aromatic, mono- or bicyclic (fused, bridged, or spiro) ring having the specified number of ring carbon atoms. In an embodiment, the cycloalkyl can be substituted or unsubstituted. In an embodiment, the cycloalkyl can be substituted with 0-4 occurrences of Ra, wherein each Rais independently selected from the group consisting of Ci-6 alkyl, C1-6 alkoxyl, and halogen.

[0195] As used herein, the term “heterocycloalkyl” refers to a stable, saturated or unsaturated or a mixture thereof, non-aromatic, mono- or bicyclic (fused, bridged, or spiro) ring radical having the specified number of ring atoms and comprising one or more heteroatoms individually selected from nitrogen, oxygen and sulfur. The heterocyclyl radical may be bonded via a carbon atom or heteroatom. In an embodiment, the specified number is C3-C12 carbons. Examples of heterocyclyl groups include, but are not limited to, azetidinyl, oxetanyl, pyrrolinyl, pyrrolidinyl, tetrahydrofuryl, tetrahydrothienyl, piperidyl, piperazinyl, tetrahydropyranyl, morpholinyl, perhydroazepinyl, tetrahydropyridinyl, tetrahydroazepinyl, octahydropyrrolopyrrolyl, and the like. The related term “heterocycloalkyl ring” likewise refers to a stable, saturated or unsaturated, non-aromatic, mono- or bicyclic (fused, bridged, or spiro) ring having the specified number of ring atoms and comprising one or more heteroatoms individually selected from nitrogen, oxygen and sulfur. In an embodiment, the heterocycloalkyl can be substituted or unsubstituted. In an embodiment, the heterocycloalkyl can be substituted with 0-4 occurrences of Ra, wherein each Rais independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxyl, and halogen. “Heterocycloalkyl” also includes ring systems wherein the heterocycloalkyl ring, as defined above, is fused with one or more cycloalkyl groups wherein the point of attachment is either on the cycloalkyl or heterocycloalkyl ring, or ring systems wherein the heterocycloalkyl ring, as defined above, is fused with one or more aryl or heteroaryl groups, wherein the point of attachment is on the heterocycloalkyl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heterocycloalkyl ring system.

[0196] As used herein, “halo” or “halogen” refers to fluorine (fluoro, -F), chlorine (chloro, -Cl), bromine (bromo, -Br), or iodine (iodo, -I).

[0197] As used herein, “haloalkyl” means an alkyl group substituted with one or more halogens. Examples of haloalkyl groups include, but are not limited to, trifluoromethyl, difluoromethyl, pentafluoroethyl, and trichloromethyl.

[0198] As used herein, “substituted”, whether preceded by the term “optionally” or not, means that one or more hydrogens of the designated moiety are replaced with a suitable substituent.

[0199] As used herein, the definition of each expression, e.g., alkyl, m, n, etc., when it occurs more than once in any structure, is intended to be independent of its definition elsewhere in the same structure.

[0200] Various embodiments of the disclosure are described herein. It will be recognized that features specified in each embodiment may be combined with other specified features, including as indicated in the embodiments below, to provide further embodiments of the present disclosure.

[0201] It is understood that in the following embodiments, combinations of substituents or variables of the depicted formulae are permissible only if such combinations result in stable compounds.

[0202] Definitions of specific functional groups and chemical terms are described in more detail below. The chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics 75thed., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Thomas Sorrell, Organic Chemistry, University Science Books, Sausalito, 1999; Smith and March, March ’s Advanced Organic Chemistry, 5thed, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; and Carruthers, Some Modern Methods of Organic Synthesis, 3rded, Cambridge University Press, Cambridge, 1987.

[0203] Certain compounds described herein may exist in particular geometric or stereoisomeric forms. If, for instance, a particular enantiomer of a compound described herein is desired, it may be prepared by asymmetric synthesis, or by derivation with a chiral auxiliary, where the resulting diastereomeric mixture is separated and the auxiliary group cleaved to provide the pure desired enantiomers. Alternatively, where the molecule contains a basic functional group, such as amino, or an acidic functional group, such as carboxyl, diastereomeric salts are formed with an appropriate optically-active acid or base, followed by resolution of the diastereomers thus formed by fractional crystallization or chromatographic means well known in the art, and subsequent recovery of the pure enantiomers.

[0204] Unless otherwise stated, structures depicted herein are also meant to include geometric (or conformational) forms of the structure; for example, the R and S configurations for each asymmetric center, cis and trans double bond isomers, Z and E double bond isomers, and Z and E conformational isomers. Therefore, single stereochemical isomers as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures of the disclosed compounds are within the scope of the disclosure. Unless otherwise stated, all tautomeric forms of the compounds described herein are within the scope of the disclosure. Additionally, unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the disclosed structures including the replacement of hydrogen by deuterium or tritium, or the replacement of a carbon by a13C or14C enriched carbon are within the scope of this disclosure. Such compounds are useful, for example, as analytical tools, as probes in biological assays, or as therapeutic agents in accordance with the disclosure.

[0205] The “enantiomeric excess” or “% enantiomeric excess” of a composition can be calculated using the equation shown below. In the example shown below a composition contains 90% of one enantiomer, e.g., the S enantiomer, and 10% of the other enantiomer, i.e., the R enantiomer, ee = (90- 10) / 100 x 100 = 80%.

[0206] Thus, a composition containing 90% of one enantiomer and 10% of the other enantiomer is said to have an enantiomeric excess of 80%. The compounds or compositions described herein may contain an enantiomeric excess of at least 50%, 75%, 90%, 95%, or 99% of one form of the compound, e.g., the S-enantiomer. In other words such compounds or compositions contain an enantiomeric excess of the S enantiomer over the R enantiomer.

[0207] Where a particular enantiomer is preferred, it may, in some embodiments be provided substantially free of the corresponding enantiomer, and may also be referred to as “optically enriched.” “Optically enriched,” as used herein, means that the compound is made up of a significantly greater proportion of one enantiomer. In certain embodiments, the compound is made up of at least about 90% by weight of a preferred enantiomer. In other embodiments, the compound is made up of at least about 95%, 98%, or 99% by weight of a preferred enantiomer. Preferred enantiomers may be isolated from racemic mixtures by any method known to those skilled in the art, including chiral high pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts or prepared by asymmetric syntheses. See e.g., Jacques et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen, et al., Tetrahedron 33:2725 (1977); Eliel, E.L. Stereochemistry of Carbon Compounds (McGraw Hill, NY, 1962); Wilen, S.H. Tables of Resolving Agents and Optical Resolutions p. 268 (E.L. Eliel, Ed., Univ, of Notre Dame Press, Notre Dame, IN 1972).

[0208] All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g. “such as”) provided herein is intended merely to better illuminate the disclosure and does not pose a limitation on the scope of the disclosure otherwise claimed.

[0209] Any resulting mixtures of isomers can be separated on the basis of the physicochemical differences of the constituents, into the pure or substantially pure geometric or optical isomers, diastereomers, racemates, for example, by chromatography and / or fractional crystallization.

[0210] Any resulting racemates of final products or intermediates can be resolved into the optical antipodes by known methods, e.g., by separation of the diastereomeric salts thereof, obtained with an optically active acid or base, and liberating the optically active acidic or basic compound. In particular, a basic moiety may thus be employed to resolve the compounds described herein into their optical antipodes, e.g., by fractional crystallization of a salt formed with an optically active acid, e.g., tartaric acid, dibenzoyl tartaric acid, diacetyl tartaric acid, di- 0,0 ’-p-toluoyl tartaric acid, mandelic acid, malic acid or camphor- 10-sulfonic acid. Racemic products can also be resolved by chiral chromatography, e.g., high pressure liquid chromatography (HPLC) using a chiral adsorbent. Pharmaceutically Acceptable Salts

[0211] Pharmaceutically acceptable salts of the compounds described herein are also contemplated for the uses described herein. As used herein, the terms “salt” or “salts” refer to an acid addition or base addition salt of a compound described herein. “Salts” include in particular “pharmaceutical acceptable salts.” The term “pharmaceutically acceptable salts” refers to salts that retain the biological effectiveness and properties of the compounds disclosed herein and, which typically are not biologically or otherwise undesirable. In many cases, the compounds disclosed herein are capable of forming acid and / or base salts by virtue of the presence of amino and / or carboxyl groups or groups similar thereto.

[0212] Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and organic acids.

[0213] Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like.

[0214] Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, toluenesulfonic acid, sulfosalicylic acid, and the like.

[0215] Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases.

[0216] Inorganic bases from which salts can be derived include, for example, ammonium salts and metals from columns I to XII of the periodic table. In certain embodiments, the salts are derived from sodium, potassium, ammonium, calcium, magnesium, iron, silver, zinc, and copper; particularly suitable salts include ammonium, potassium, sodium, calcium, and magnesium salts.

[0217] Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, and the like. Certain organic amines include isopropylamine, benzathine, cholinate, diethanolamine, diethylamine, lysine, meglumine, piperazine, and tromethamine.

[0218] Another embodiment is a compound of Formula (I) or subformula thereof as an acetate, ascorbate, adipate, aspartate, benzoate, besylate, bromide / hydrobromide, bicarbonate / carbonate, bisulfate / sulfate, camphorsulfonate, caprate, chloride / hydrochloride, chi ortheophyll onate, citrate, ethandi sulfonate, fumarate, gluceptate, gluconate, glucuronate, glutamate, glutarate, glycolate, hippurate, hydroiodide / iodide, isethionate, lactate, lactobionate, laurylsulfate, malate, maleate, malonate, mandelate, mesylate, methyl sulphate, mucate, naphthoate, napsylate, nicotinate, nitrate, octadecanoate, oleate, oxalate, palmitate, pamoate, phosphate / hydrogen phosphate / dihydrogen phosphate, polygalacturonate, propionate, sebacate, stearate, succinate, sulfosalicylate, sulfate, tartrate, tosylate trifenatate, trifluoroacetate, or xinafoate salt form. Pharmaceutical Compositions

[0219] Another embodiment is a pharmaceutical composition comprising one or more compounds described herein or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and one or more pharmaceutically acceptable carrier(s). The term “pharmaceutically acceptable carrier” refers to a pharmaceutically-acceptable material, composition or vehicle, such as a liquid or solid fdler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting any subject composition or component thereof. Each carrier must be “acceptable” in the sense of being compatible with the subject composition and its components and not injurious to the patient. Some examples of materials which may serve as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer’s solution; (19) ethyl alcohol; (20) phosphate buffer solutions; and (21) other non-toxic compatible substances employed in pharmaceutical formulations.

[0220] The compositions described herein may be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, buccally, vaginally or via an implanted reservoir. The term “parenteral” as used herein includes subcutaneous, intravenous, intramuscular, intraarticular, intra-synovial, intrastemal, intrathecal, intrahepatic, intralesional and intracranial injection or infusion techniques. In some embodiments, the compositions of the disclosure are administered orally, intraperitoneally or intravenously. Sterile injectable forms of the compositions of this disclosure may be aqueous or oleaginous suspension. These suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example as a solution in 1,3 -butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer’s solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium.

[0221] For this purpose, any bland fixed oil may be employed including synthetic mono- or diglycerides. Fatty acids, such as oleic acid and its glyceride derivatives are useful in the preparation of injectables, as are natural pharmaceutically-acceptable oils, such as olive oil or castor oil, especially in their polyoxy ethylated versions. These oil solutions or suspensions may also contain a long-chain alcohol diluent or dispersant, such as carboxymethyl cellulose or similar dispersing agents that are commonly used in the formulation of pharmaceutically acceptable dosage forms including emulsions and suspensions. Other commonly used surfactants, such as Tween®, Spans and other emulsifying agents or bioavailability enhancers which are commonly used in the manufacture of pharmaceutically acceptable solid, liquid, or other dosage forms may also be used for the purposes of formulation.

[0222] The pharmaceutically acceptable compositions described herein may be orally administered in any orally acceptable dosage form including, but not limited to, capsules, tablets, aqueous suspensions or solutions. In the case of tablets for oral use, carriers commonly used include lactose and com starch. Lubricating agents, such as magnesium stearate, are also typically added. For oral administration in a capsule form, useful diluents include lactose and dried cornstarch. When aqueous suspensions are required for oral use, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening, flavoring or coloring agents may also be added.

[0223] Alternatively, the pharmaceutically acceptable compositions of this disclosure may be administered in the form of suppositories for rectal administration. These can be prepared by mixing the agent with a suitable non-irritating excipient that is solid at room temperature but liquid at rectal temperature and therefore will melt in the rectum to release the drug. Such materials include cocoa butter, beeswax, and polyethylene glycols. The pharmaceutically acceptable compositions of this disclosure may also be administered topically, especially when the target of treatment includes areas or organs readily accessible by topical application, including diseases of the eye, the skin, or the lower intestinal tract. Suitable topical formulations are readily prepared for each of these areas or organs. Topical application for the lower intestinal tract can be effected in a rectal suppository formulation (see above) or in a suitable enema formulation. Topically-transdermal patches may also be used.

[0224] For topical applications, the pharmaceutically acceptable compositions may be formulated in a suitable ointment containing the active component suspended or dissolved in one or more carriers. Carriers for topical administration of the compounds of this disclosure include, but are not limited to, mineral oil, liquid petrolatum, white petrolatum, propylene glycol, polyoxyethylene, polyoxypropylene compound, emulsifying wax and water. Alternatively, the pharmaceutically acceptable compositions can be formulated in a suitable lotion or cream containing the active components suspended or dissolved in one or more pharmaceutically acceptable carriers. Suitable carriers include, but are not limited to, mineral oil, sorbitan monostearate, polysorbate 60, cetyl esters wax, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol, and water.

[0225] The pharmaceutically acceptable compositions of this disclosure may also be administered by nasal aerosol or inhalation. Such compositions are prepared according to techniques well-known in the art of pharmaceutical formulation and may be prepared as solutions in saline, employing benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, fluorocarbons, and / or other conventional solubilizing or dispersing agents. The amount of the compounds of the present disclosure that may be combined with the carrier materials to produce a composition in a single dosage form will vary depending upon the host treated, the particular mode of administration. Preferably, the compositions should be formulated so that a dosage of between 0.01-100 mg / kg body weight / day of the inhibitor can be administered to a patient receiving these compositions.

[0226] Isotopically Labelled Compounds

[0227] A compound described herein or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, is also intended to represent unlabeled forms as well as isotopically labeled forms of the compounds. Isotopically labeled compounds have structures depicted by the formulas given herein except that one or more atoms are replaced by an atom having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into compounds described herein include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine, and chlorine, such as2H, 3H,nC,13C,14C,15N,18F,31P,32P,33S,36C1,123I,124I,12?I, respectively. The disclosure includes various isotopically labeled compounds as defined herein, for example, those into which radioactive isotopes, such as3H and14C, or those into which non-radioactive isotopes, such as2H and13C are present. Such isotopically labelled compounds are useful in metabolic studies (with14C), reaction kinetic studies (with, for example2H or3H), detection or imaging techniques, such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT) including drug or substrate tissue distribution assays, or in radioactive treatment of patients. In particular, an18F or labeled compound may be particularly desirable for PET or SPECT studies. Isotopically-labeled compounds described herein or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described in the accompanying Examples and Preparations using an appropriate isotopically-labeled reagents in place of the non-labeled reagent previously employed.

[0228] Further, substitution with heavier isotopes, particularly deuterium (i.e.,2H or D) may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements or an improvement in therapeutic index. It is understood that deuterium in this context is regarded as a substituent of a compound described herein or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. The concentration of such a heavier isotope, specifically deuterium, may be defined by the isotopic enrichment factor. The term “isotopic enrichment factor” as used herein means the ratio between the isotopic abundance and the natural abundance of a specified isotope. If a substituent in a compound described herein is denoted deuterium, such compound has an isotopic enrichment factor for each designated deuterium atom of at least 3500 (52.5% deuterium incorporation at each designated deuterium atom), at least 4000 (60% deuterium incorporation), at least 4500 (67.5% deuterium incorporation), at least 5000 (75% deuterium incorporation), at least 5500 (82.5% deuterium incorporation), at least 6000 (90% deuterium incorporation), at least 6333.3 (95% deuterium incorporation), at least 6466.7 (97% deuterium incorporation), at least 6600 (99% deuterium incorporation), or at least 6633.3 (99.5% deuterium incorporation). Dosages

[0229] Toxicity and therapeutic efficacy of compounds described herein, including pharmaceutically acceptable salts and deuterated variants, can be determined by standard pharmaceutical procedures in cell cultures or experimental animals. The LD50 is the dose lethal to 50% of the population. The ED50 is the dose therapeutically effective in 50% of the population. The dose ratio between toxic and therapeutic effects (LD50 / ED50) is the therapeutic index. Compounds that exhibit large therapeutic indexes are preferred. While compounds that exhibit toxic side effects may be used, care should be taken to design a delivery system that targets such compounds to the site of affected tissue in order to minimize potential damage to uninfected cells and thereby reduce side effects.

[0230] Data obtained from the cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. The dosage of such compounds may lie within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. For any compound, the therapeutically effective dose can be estimated initially from cell culture assays. A dose may be formulated in animal models to achieve a circulating plasma concentration range that includes the IC50 (i.e., the concentration of the test compound that achieves a half-maximal inhibition of symptoms) as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Levels in plasma may be measured, for example, by high performance liquid chromatography.

[0231] It should also be understood that a specific dosage and treatment regimen for any particular patient will depend upon a variety of factors, including the activity of the specific compound employed, the age, body weight, general health, sex, diet, time of administration, rate of excretion, drug combination, and the judgment of the treating physician and the severity of the particular disease being treated. The amount of a compound described herein in the composition will also depend upon the particular compound in the composition.

[0232] Methods of Use

[0233] In one aspect, the present disclosure features a method of modulating a target protein, e.g., a target protein described herein, in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. In some embodiments, the modulating comprises one or more of: (i) modulating the folding of the target protein; (ii) modulating the half-life of the target protein; (iii) modulating trafficking of the target protein to the proteasome; (iv) modulating the level of ubiquitination of the target protein; (v) modulating degradation (e.g., proteasomal degradation) of the target protein; (vi) modulating target protein signaling; (vii) modulating target protein localization; (viii) modulating trafficking of the target protein to the lysosome; and (ix) modulating target protein interactions with another protein.

[0234] In another aspect, the present disclosure features a method of degrading a target protein, e.g., a target protein described herein, in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. In some embodiments, the degrading comprises decreasing the half-life of a target protein or facilitating the addition of a Ubl onto a target protein, e.g., compared to a reference standard. In some embodiments, the degrading comprises reducing the function of a target protein.

[0235] In another aspect, the present disclosure features a method of forming a protein complex comprising a RING E3 ligase, e.g., a RING E3 ligase described herein, and a target protein, upon administration of a compound of Formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. In some embodiments, the protein complex is formed in vitro (e.g., in a sample) or in vivo (e.g., in a cell or tissue, e.g., in a subject). Formulation of the protein complex may be observed and characterized by any method known in the art, e.g., mass spectrometry (native mass spectrometry) or SDS PAGE. In some embodiments, forming the protein complex modulates the level of a target protein, e.g., decreases the half-life of the target protein, e.g., compared to a reference standard. In some embodiments, forming the protein facilitates addition of a Ubl onto a target protein, e.g., compared to a reference standard. In some embodiments, the RING E3 ubiquitin ligase is RNF126.

[0236] Another embodiment is a method for adding a Ubl (e.g., a ubiquitin or ubiquitin-like protein) onto a target protein, e.g., a target protein described herein, the method comprising contacting a target protein with an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. In another aspect, the present disclosure provides a method of reducing or inhibiting the activity of a target protein, e.g., a target protein described herein, the method comprising contacting a target protein with an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0237] In an embodiment, reducing or inhibiting the activity of a target protein comprises binding to a RING E3 ubiquitin ligase with the molecular glue compound described herein, e.g., a compound of Formula (I), forming a ternary complex of the target protein, the molecular glue compound, and the RING E3 ubiquitin ligase, to thereby reduce or inhibit the activity of the target protein.

[0238] In another aspect, the present disclosure features a method of treating or preventing a disease, disorder or condition mediated by a target protein, e.g., a target protein described herein, the method comprising administering to the subject a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. In some embodiments, the disease, disorder, or condition is selected from the group consisting of a respiratory disorder, a proliferative disorder, an autoimmune disorder, an autoinflammatory disorder, an inflammatory disorder, a metabolic disorder, a neurological disorder, and an infectious disease. In some embodiments, the disease, disorder, or condition is selected from the group consisting of a respiratory disorder, a proliferative disorder, an autoimmune disorder, an autoinflammatory disorder, an inflammatory disorder, a neurological disorder, and an infectious disease. In some embodiments, the disease, disorder, or condition comprises a respiratory disorder. In some embodiments, the disease, disorder, or condition comprises a proliferative disorder. In some embodiments, the disease, disorder, or condition comprises an autoinflammatory disorder. In some embodiments, the disease, disorder, or condition comprises an inflammatory disorder. In some embodiments, the disease, disorder, or condition comprises a metabolic disorder. In some embodiments, the disease, disorder, or condition comprises a neurological disorder. In some embodiments, the disease, disorder, or condition comprises an infectious disease.

[0239] In some embodiments, the proliferative disorder is cancer. As used herein, the term “cancer” refers to a malignant neoplasm (Stedman’s Medical Dictionary, 25th ed.; Hensyl ed.; Williams & Wilkins: Philadelphia, 1990). The cancer may involve any organ, tissue, or cell in the body. All types of cancers disclosed herein or known in the art are contemplated as being within the scope of the disclosure. Exemplary cancers include, but are not limited to, acoustic neuroma; adenocarcinoma; adrenal gland cancer; anal cancer; angiosarcoma (e.g., lymphangiosarcoma, lymphangioendotheliosarcoma, hemangiosarcoma); appendix cancer; benign monoclonal gammopathy; biliary cancer (e.g., cholangiocarcinoma); bladder cancer; breast cancer (e.g., adenocarcinoma of the breast, papillary carcinoma of the breast, mammary cancer, medullary carcinoma of the breast); brain cancer (e.g., meningioma, glioblastomas, glioma (e.g., astrocytoma, oligodendroglioma), medulloblastoma); bronchus cancer; carcinoid tumor; cervical cancer (e.g., cervical adenocarcinoma); choriocarcinoma; chordoma; craniopharyngioma; colorectal cancer (e.g., colon cancer, rectal cancer, colorectal adenocarcinoma); connective tissue cancer; epithelial carcinoma; ependymoma; endotheliosarcoma (e.g., Kaposi’s sarcoma, multiple idiopathic hemorrhagic sarcoma); endometrial cancer (e.g., uterine cancer, uterine sarcoma); esophageal cancer (e.g., adenocarcinoma of the esophagus, Barrett’s adenocarcinoma); Ewing’s sarcoma; eye cancer (e.g., intraocular melanoma, retinoblastoma); familiar hypereosinophilia; gall bladder cancer; gastric cancer (e.g., stomach adenocarcinoma); gastrointestinal stromal tumor (GIST); germ cell cancer; head and neck cancer (e.g., head and neck squamous cell carcinoma, oral cancer (e.g., oral squamous cell carcinoma), throat cancer (e.g., laryngeal cancer, pharyngeal cancer, nasopharyngeal cancer, oropharyngeal cancer), e.g., adenoid cystic carcinoma (ACC)); hematopoietic cancers (e.g., leukemia such as acute lymphocytic leukemia (ALL) (e.g., B-cell ALL, T-cell ALL), acute myelocytic leukemia (AML) (e.g., B-cell AML, T-cell AML), chronic myelocytic leukemia (CML) (e.g., B-cell CML, T-cell CML), and chronic lymphocytic leukemia (CLL) (e g., B-cell CLL, T-cell CLL)); lymphoma such as Hodgkin lymphoma (HL) (e.g., B-cell HL, T-cell HL) and non-Hodgkin lymphoma (NHL) (e.g., B-cell NHL such as diffuse large cell lymphoma (DLCL) (e.g., diffuse large B-cell lymphoma), follicular lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), mantle cell lymphoma (MCL), marginal zone B-cell lymphomas (e.g., mucosa-associated lymphoid tissue (MALT) lymphomas, nodal marginal zone B-cell lymphoma, splenic marginal zone B-cell lymphoma), primary mediastinal B-cell lymphoma, Burkitt lymphoma, lymphoplasmacytic lymphoma (i.e., Waldenstrom’s macroglobulinemia), hairy cell leukemia (HCL), immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma and primary central nervous system (CNS) lymphoma; and T-cell NHL such as precursor T-lymphoblastic lymphoma / leukemia, peripheral T-cell lymphoma (PTCL) (e.g., cutaneous T-cell lymphoma (CTCL) (e.g., mycosis fungoides, Sezary syndrome), angioimmunoblastic T-cell lymphoma, extranodal natural killer T-cell lymphoma, enteropathy type T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, and anaplastic large cell lymphoma); a mixture of one or more leukemia / lymphoma as described above; and multiple myeloma (MM)), heavy chain disease (e.g., alpha chain disease, gamma chain disease, mu chain disease); hemangioblastoma; hypopharynx cancer; inflammatory myofibroblastic tumors; immunocytic amyloidosis; kidney cancer (e.g., nephroblastoma a.k.a. Wilms’ tumor, renal cell carcinoma); liver cancer (e.g., hepatocellular cancer (HCC), malignant hepatoma); lung cancer (e.g., bronchogenic carcinoma, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), adenocarcinoma of the lung); leiomyosarcoma (LMS); mastocytosis (e.g., systemic mastocytosis); muscle cancer; myelodysplastic syndrome (MDS); mesothelioma; myeloproliferative disorder (MPD) (e g., polycythemia vera (PV), essential thrombocytosis (ET), agnogenic myeloid metaplasia (AMM) a.k.a. myelofibrosis (MF), chronic idiopathic myelofibrosis, chronic myelocytic leukemia (CML), chronic neutrophilic leukemia (CNL), hypereosinophilic syndrome (HES)); neuroblastoma; neurofibroma (e.g., neurofibromatosis (NF) type 1 or type 2, schwannomatosis); neuroendocrine cancer (e.g., gastroenteropancreatic neuroendocrine tumor (GEP-NET), carcinoid tumor); osteosarcoma (e.g., bone cancer); ovarian cancer (e.g., cystadenocarcinoma, ovarian embryonal carcinoma, ovarian adenocarcinoma); papillary adenocarcinoma; pancreatic cancer (e.g., pancreatic adenocarcinoma, intraductal papillary mucinous neoplasm (IPMN), Islet cell tumors); penile cancer (e.g., Paget’s disease of the penis and scrotum); pinealoma; primitive neuroectodermal tumor (PNT); plasma cell neoplasia; paraneoplastic syndromes; intraepithelial neoplasms; prostate cancer (e.g., prostate adenocarcinoma); rectal cancer; rhabdomyosarcoma; salivary gland cancer; skin cancer (e.g., squamous cell carcinoma (SCC), keratoacanthoma (KA), melanoma, basal cell carcinoma (BCC)); small bowel cancer (e.g., appendix cancer); soft tissue sarcoma (e.g., malignant fibrous histiocytoma (MFH), liposarcoma, malignant peripheral nerve sheath tumor (MPNST), chondrosarcoma, fibrosarcoma, myxosarcoma); sebaceous gland carcinoma; small intestine cancer; sweat gland carcinoma; synovioma; testicular cancer (e.g., seminoma, testicular embryonal carcinoma); thyroid cancer (e.g., papillary carcinoma of the thyroid, papillary thyroid carcinoma (PTC), medullary thyroid cancer); urethral cancer; vaginal cancer; and vulvar cancer (e.g., Paget’s disease of the vulva). In some embodiments, the proliferative disorder is associated with a benign neoplasm. For example, a benign neoplasm may include adenoma, fibroma, hemangioma, tuberous sclerosis, and lipoma. All types of benign neoplasms disclosed herein or known in the art are contemplated as being within the scope of the disclosure.

[0240] In some embodiments, the target protein is BRD4 and the cancer is selected from diffuse large B cell lymphoma, acute myeloid leukemia (AML) (e.g., B-cell AML, T-cell AML), prostate cancer (e.g., prostate adenocarcinoma), and breast cancer. In some embodiments, the target protein is BCR-Abl and the cancer is selected from chronic myelogenous leukemia (CML), acute myeloid leukemia (AML) (e.g., B-cell AML, T-cell AML), and acute lymphoblastic leukemia (ALL). In some embodiments, the target protein is c-ABL and the cancer is chronic myelogenous leukemia (CML). In some embodiments, the target protein is PDE5 and the disease, disorder, or condition is selected from a cardiovascular disease (e.g., hypertension), metabolic disease (e.g., diabetes), cancer, or erectile dysfunction. In some embodiments, the target protein is AR or AR-v7 and the disease, disorder, or condition is related to sex development in a subject or cancer (e.g., prostate cancer or breast cancer). In some embodiments, the target protein is BTK and the disease, disorder, or condition is selected from cancer (mantle cell lymphoma, chronic lymphocytic leukemia (CLL), B-cell lymphoma), or multiple sclerosis. In some embodiments, the target protein is LRRK2 and the disease, disorder, or condition is selected from a neurodegenerative disease, such as Parkinson’s disease. In some embodiments, the target protein is SMARCA2 and the disease, disorder, or condition is selected from a cancer.

[0241] In another aspect, the disclosure provides a compound of Formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, for use in inhibiting or modulating a target protein in a subject in need thereof.

[0242] Another embodiment is a use of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, in the manufacture of a medicament for treating or preventing a respiratory disorder, a proliferative disorder, an autoimmune disorder, an autoinflammatory disorder, an inflammatory disorder, a neurological disorder, and an infectious disease or disorder in a subject in need thereof.

[0243] EXEMPLARY ENUMERATED EMBODIMENTS 1 . A molecular glue degrader compound of Formula (I):

[0244] Target Ligand - 1 Bridge ! - RING E3 Ligase Binder

[0245] ' - ' ' - ' ' - - - ' (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein:

[0246] (i) the Target Ligand is capable of binding to a target protein;

[0247] (ii) Bridge is absent or a linker; and

[0248] (iii) the RING E3 Ligase Binder is capable of binding to a RING E3 ubiquitin ligase (e.g., RNF126 or BCA2).

[0249] 2. The molecular glue degrader compound of embodiment 1, wherein the target protein selected from a tyrosine kinase, a serine / threonine kinase, a bromodomain-containing protein, an epigenetic protein, and a misfolded protein.

[0250] 3. The molecular glue degrader compound of any one of embodiments 1-2, wherein the target protein is selected from AR, BCL-2 / BCL, BCL-XL, BCR-ABL, BRD2, BRD3, BRIM, BRD9, BRDT, BTK, BUB1, BUB IB, c-ABL, CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK1 IB, CDK12, CDK13, CDK14, CDK15, CDK16, CDK17, CDK18, CDK19, CDK20, CHEK1, CKS1B, CKS2, CSNK1A1, CSNK1E, CTNNB1, DSTYK, EEF2K, estrogen receptor (ER), ETNK1, FASTKD5, HRAS, ITPKB, KRAS, LRKK2, MAPKAPK2 (MK2), MARK2, MAP3K2, MELK, MYC, MYCN, NEK6, NRAS, PANK2, PANK3, PDE5, PHKA1, PHKA2, PKN2, PLK1, PTK6, RIOK2, SKP2, SMARCA2, SMARCA4, STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6, TK1, TTK, and UCK2.

[0251] 4. The molecular glue degrader compound of any one of embodiments 1-3, wherein the target protein is selected from AR-V7, Bcl-2 / Bcl, BCR-ABL, BRIM, BTK, BUB1, BUB1B, c- ABL, CDK4, CDK11B, CHEK1, CKS1B, CKS2, CSNK1A1, CSNK1E, DSTYK, EEF2K, ETNK1, FASTKD5, ITPKB, KRAS G12D, LRKK2, MARK2, MAP3K2, MELK, NEK6, PANK2, PANK3, PDE5, PHKA1, PHKA2, PKN2, PLK1, RIOK2, SKP2, SMARCA2, TK1, TTK, and UCK2. 5. The molecular glue degrader compound of any one of embodiments 1-4, wherein the target protein is selected from CDK4, CDK6, BRD4, PDE5, BCR-ABL, c-ABL, AR, AR-V7, BTK, LRKK2, or SMARCA2.

[0252] 6. The molecular glue degrader compound of any one of embodiments 1-5, wherein the target protein is AR or AR-V7.

[0253] 7. The molecular glue degrader compound of any one of the preceding embodiments, wherein the molecular glue degrader compound has the structure of Formula (II): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0254] X is O or S;

[0255] Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7;

[0256] — IJ Target Ligand

[0257] R1is

[0258] L1is a linker selected from the group of alkyl, heteroalkyl, C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRD-C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I);

[0259] Target Ligand comprises a moiety capable of binding to a target protein;

[0260] R2is selected from the group consisting of hydrogen and Ci-6 alkyl; or

[0261] R1and R2together with the atoms to which they are attached form a 5- to 10-membered heteroaryl or a 3- to 12-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0262] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;

[0263] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0264] R6aand R6b, together with the atoms to which they are attached, form an oxo group;

[0265] R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl;

[0266] — L Target Ligand

[0267] R8is

[0268] L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3- cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R1?is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0269] RBis hydrogen or Ci-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, or 4. 8. A molecular glue degrader compound of embodiment 7, wherein Ring A is 6- to 10- membered aryl, 5- to 10-membered heteroaryl, 3- to 12-membered cycloalkyl, or 3- to 12- membered heterocycloalkyl, each of which is optionally substituted with one or more R7.

[0270] 9. A molecular glue degrader compound of any one of embodiments 7-8, wherein Ring A is aryl or heteroaryl, each of which is optionally substituted with one or more R7.

[0271] 10. A molecular glue degrader compound of any one of embodiments 7-9, wherein Ring A is aryl, optionally substituted with one or more R7.

[0272] 11. A molecular glue degrader compound of any one of embodiments 7-10, wherein Ring A is monocyclic or bicyclic aryl, optionally substituted with one or more R7.

[0273] 12. A molecular glue degrader compound of any one of embodiments 7-11, wherein Ring A is monocyclic aryl, optionally substituted with one or more R7.

[0274] 13. A molecular glue degrader compound of any one of embodiments 7-12, wherein Ring A is 6- to 10-membered aryl (e.g., phenyl), optionally substituted with one or more R7.

[0275] 14. A molecular glue degrader compound of any one of embodiments 7-13, wherein Ring A is 6-membered aryl (e.g., phenyl), optionally substituted with one or more R7.

[0276] 15. A molecular glue degrader compound of any one of embodiments 7-14, wherein Ring A is phenyl, optionally substituted with one or more R7.

[0277] 16. A molecular glue degrader compound of any one of embodiments 7-15, wherein Ring A is an 8-membered aryl, optionally substituted with one or more R7.

[0278] 17. A molecular glue degrader compound of any one of embodiments 7-16, wherein Ring A is a 10-membered aryl, optionally substituted with one or more R7. 18. A molecular glue degrader compound of any one of embodiments 7-17, wherein Ring A is an aryl ring, optionally substituted with two or more R7, wherein two R7on adjacent atoms together with the atoms to which they are attached form an optionally substituted heterocycloalkyl ring.

[0279] 19. A molecular glue degrader compound of any one of embodiments 7-18, wherein Ring A is an aryl ring, optionally substituted with two or more R7, wherein two R7on adjacent atoms together with the atoms to which they are attached form an optionally substituted heterocycloalkyl ring containing 1 or 2 O or N atoms.

[0280] 20. A molecular glue degrader compound of any one of embodiments 7-19, wherein Ring A

[0281] 21 . A molecular glue degrader compound of any one of embodiments 7-20, wherein Ring A 22. A molecular glue degrader compound of any one of embodiments 7-21, wherein Ring A

[0282] 23. A molecular glue degrader compound of any one of embodiments 7-22, wherein Ring A

[0283] 24. A molecular glue degrader compound of any one of embodiments 7-23, wherein Ring A

[0284]

[0285] 5 25. A molecular glue degrader compound of any one of embodiments 7-24, wherein Ring A 26. A molecular glue degrader compound of any one of embodiments 7-25, wherein Ring A

[0286] 27. A molecular glue degrader compound of any one of embodiments 7-26, wherein Ring A 28. A molecular glue degrader compound of any one of embodiments 7-27, wherein Ring A

[0287] 29. A molecular glue degrader compound of any one of embodiments 7-28, wherein Ring A is selected from

[0288] 30. A molecular glue degrader compound of any one of embodiments 7-29, wherein Ring A 31. A molecular glue degrader compound of any one of embodiments 7-30, wherein Ring A

[0289] 32. A molecular glue degrader compound of any one of embodiments 7-31, wherein X is O.

[0290] 33. A molecular glue degrader compound of any one of embodiments 7-31, wherein X is S.

[0291] 34. A molecular glue degrader compound of any one of embodiments 7-33, wherein R1is

[0292] — L1- Target Ligand

[0293] 35. A molecular glue degrader compound of any one of embodiments 7-34, wherein L1is selected from C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloal kyl -NRB-C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I).

[0294] 36. A molecular glue degrader compound of any one of embodiments 7-35, wherein L1is selected from -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I).

[0295] 37. A molecular glue degrader compound of any one of embodiments 7-36, wherein L1is-C2- 5 cycloalkyl-NRB-*, optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I). 38. A molecular glue degrader compound of any one of embodiments 7-37, wherein L1is - C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I).

[0296] 39. A molecular glue degrader compound of any one of embodiments 7-38, wherein L1is - C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I).

[0297] 40. A molecular glue degrader compound of any one of embodiments 7-39, wherein L1is -C4 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, optionally substituted with one or more R13, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I).

[0298] 41. A molecular glue degrader compound of any one of embodiments 7-40, wherein L1is -C4 cycloalkyl-NRB-C(O)-CH2-O-*, optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I).

[0299] 42. A molecular glue degrader compound of any one of embodiments 7-41, wherein L1is - cyclobutyl-NH-C(O)-CH2-O-*, optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I).

[0300] 43. A molecular glue degrader compound of any one of embodiments 7-42, wherein R2is hydrogen or C1-4 alkyl.

[0301] 44. A molecular glue degrader compound of any one of embodiments 7-43, wherein R2is hydrogen or -CH3.

[0302] 45. A molecular glue degrader compound of any one of embodiments 7-44, wherein R2is hydrogen.

[0303] 46. A molecular glue degrader compound of any one of embodiments 7-45, wherein R2is - CH3. 47. A molecular glue degrader compound of any one of embodiments 7-46, wherein R1and R2together with the atoms to which they are attached form a heteroaryl or a heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9.

[0304] 48. A molecular glue degrader compound of any one of embodiments 7-47, wherein R1and R2together with the atoms to which they are attached form a 5- to 10-membered heteroaryl or a 3- to 12-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9.

[0305] 49. A molecular glue degrader compound of any one of embodiments 7-48, wherein R1and R2together with the atoms to which they are attached form a 5- to 6-membered heteroaryl or a 5- to 8-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9.

[0306] 50. A molecular glue degrader compound of any one of embodiments 7-49, wherein R1and R2together with the atoms to which they are attached form a heterocycloalkyl ring, comprising 1, 2, or 3 heteroatoms.

[0307] 51. A molecular glue degrader compound of any one of embodiments 7-50, wherein R1and R2together with the atoms to which they are attached form a monocyclic or bicyclic heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9.

[0308] 52. A molecular glue degrader compound of any one of embodiments 7-51, wherein R1and R2together with the atoms to which they are attached form a monocyclic heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9. 53. A molecular glue degrader compound of any one of embodiments 7-52, wherein R1and R2together with the atoms to which they are attached form a 3- to 12-membered heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9.

[0309] 54. A molecular glue degrader compound of any one of embodiments 7-53, wherein R1and R2together with the atoms to which they are attached form a 5- to 8-membered heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9.

[0310] 55. A molecular glue degrader compound of any one of embodiments 7-54, wherein R1and R2together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9.

[0311] 56. A molecular glue degrader compound of any one of embodiments 7-55, wherein R1and R2together with the atoms to which they are attached form a 6-membered heterocycloalkyl (e.g. piperazinyl), substituted with one R8, and optionally substituted with 1-4 occurrences of R9.

[0312] 57. A molecular glue degrader compound of any one of embodiments 7-56, wherein R1and

[0313] R2together with the atoms to which they are attached form a heterocycloalkyl ring selected from:

[0314] 58. A molecular glue degrader compound of any one of embodiments 7-57, wherein R1and

[0315] R2together with the atoms to which they are attached form a heterocycloalkyl ring selected from:

[0316]

[0317] 59. A molecular glue degrader compound of any one of embodiments 7-58, wherein R1and

[0318] R2together with the atoms to which they are attached form

[0319] 60. A molecular glue degrader compound of any one of embodiments 7-59, wherein L2is absent.

[0320] 61. A molecular glue degrader compound of any one of embodiments 7-60, wherein L2is a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene-*, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I).

[0321] 62. A molecular glue degrader compound of any one of embodiments 7-61, wherein L2is selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene-*, -C(0)-Co-4 heteroal kylene- *, and -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I).

[0322] 63. A molecular glue degrader compound of any one of embodiments 7-62, wherein L2is selected from -C(0)-Co-4 heteroalkylene-* and -C(0)-Co-4 alkylene-O-*, wherein each heteroalkylene and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I). 64. A molecular glue degrader compound of any one of embodiments 7-63, wherein L2is - C(0)-Co-4 alkylene-O-*, wherein the alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I).

[0323] 65. A molecular glue degrader compound of any one of embodiments 7-64, wherein L2is absent or -C(0)-Co-4 alkylene-O-*, wherein the alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula

[0324] (I).

[0325] 66. A molecular glue degrader compound of any one of embodiments 7-65, wherein , L2is - C(O)-C(R13a)(R15b)-O-*, wherein R15aan R15bare independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; and wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I).

[0326] 67. A molecular glue degrader compound of any one of embodiments 7-66, wherein the Target Ligand is a kinase inhibitor, bromodomain inhibitor, or phosphodiesterase inhibitor.

[0327] 68. A molecular glue degrader compound of any one of embodiments 7-67, wherein the Target Ligand is capable of binding to CDK4, CDK6, BRD4, PDE5, BCR-ABL, c-ABL, AR, AR-V7, BTK, LRRK2, or SMARCA2.

[0328] 69. A molecular glue degrader compound of any one of embodiments 7-68, wherein the Target Ligand is selected from ribociclib, dasatinib, palbociclib, sildenafd, HG-10-102-01, JQ1, ibrutinib, or a derivative thereof.

[0329] 70. A molecular glue degrader compound of any one of embodiments 7-69, wherein the

[0330] Target Ligand i of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; R13is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; and q is 0, 1, 2, 3, or 4.

[0331] 71. A molecular glue degrader compound of any one of embodiments 7-70, wherein R11is selected from -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, and Ci-6 haloalkyl.

[0332] 72. A molecular glue degrader compound of any one of embodiments 7-71, wherein R11is selected from -OH and Ci-6 alkyl.

[0333] 73. A molecular glue degrader compound of any one of embodiments 7-72, wherein R12is hydrogen, halogen, or Ci-6 alkyl.

[0334] 74. A molecular glue degrader compound of any one of embodiments 7-73, wherein R12is hydrogen or C 1.6 alkyl.

[0335] 75. A molecular glue degrader compound of any one of embodiments 7-74, wherein each R13is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl.

[0336] 76. A molecular glue degrader compound of any one of embodiments 7-75, wherein R13is hydrogen.

[0337] 77. A molecular glue degrader compound of any one of embodiments 7-76, wherein q is 0, 1, or 2.

[0338] 78. A molecular glue degrader compound of any one of embodiments 7-77, wherein q is 0 or 1. 79. A molecular glue degrader compound of any one of embodiments 7-78, wherein q is 0.

[0339] 80. A molecular glue degrader compound of any one of embodiments 7-79, wherein the

[0340] Target Ligand i

[0341] 81. A molecular glue degrader compound of any one of embodiments 7-80, wherein R3aand R3bare each independently selected from hydrogen, -OH, halogen, and Ci-6 alkyl.

[0342] 82. A molecular glue degrader compound of any one of embodiments 7-81, wherein R3aand R3bare each independently selected from hydrogen and Ci-6 alkyl.

[0343] 83. A molecular glue degrader compound of any one of embodiments 7-82, wherein R3aand R3bare each independently hydrogen.

[0344] 84. A molecular glue degrader compound of any one of embodiments 7-83, wherein R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, and Ci-6 alkyl.

[0345] 85. A molecular glue degrader compound of any one of embodiments 7-84, wherein R4and R3are each independently selected from the group consisting of hydrogen and Ci-6 alkyl.

[0346] 86. A molecular glue degrader compound of any one of embodiments 7-85, wherein R4and R5are each independently hydrogen.

[0347] 87. A molecular glue degrader compound of any one of embodiments 7-86, wherein R6aand R6bare each independently selected from hydrogen, -OH, halogen, and Ci-6 alkyl. 88. A molecular glue degrader compound of any one of embodiments 7-87, wherein R6aand R6bare each independently selected from the group consisting of hydrogen and Ci-6 alkyl (e.g., - CH3).

[0348] 89. A molecular glue degrader compound of any one of embodiments 7-88, wherein R6aand R6bare each independently hydrogen.

[0349] 90. A molecular glue degrader compound of any one of embodiments 7-86, wherein R6aand R6b, together with the atoms to which they are attached, form an oxo group.

[0350] 91. A molecular glue degrader compound of any one of embodiments 7-90, wherein each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, and Ci-6 haloalkyl.

[0351] 92. A molecular glue degrader compound of any one of embodiments 7-91, wherein each R7is independently selected from halogen, Ci-6 alkoxyl, and Ci-6 haloalkyl.

[0352] 93. A molecular glue degrader compound of any one of embodiments 7-92, wherein each R7is independently selected from halogen and Ci-6 alkoxyl.

[0353] 94. A molecular glue degrader compound of any one of embodiments 7-93, wherein R7is halogen (e.g., -Cl, -F, -Br, -I).

[0354] 95. A molecular glue degrader compound of any one of embodiments 7-94, wherein R7is - Cl.

[0355] 96. A molecular glue degrader compound of any one of embodiments 7-93, wherein R7is Ci- 6 alkoxyl (e.g., -OCH3).

[0356] 97. A molecular glue degrader compound of embodiment 96, wherein R7is -OCH3. 98. A molecular glue degrader compound of any one of embodiments 7-97, wherein each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci- 6 haloalkyl, and Ci-6 haloalkoxyl.

[0357] 99. A molecular glue degrader compound of any one of embodiments 7-98, wherein R9is Ci- 6 alkyl (e.g., methyl, ethyl, propyl).

[0358] 100. A molecular glue degrader compound of any one of embodiments 7-97, wherein two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo.

[0359] 101. A molecular glue degrader compound of embodiment 100, wherein two R9on the same carbon atom together with the same carbon atom to which they are attached form an oxo.

[0360] 102. A molecular glue degrader compound of any one of embodiments 7-101, wherein each R15is independently selected from hydrogen, -OH, halogen, C1-6 alkyl, and Ci-6 haloalkyl.

[0361] 103. A molecular glue degrader compound of any one of embodiments 7-102, wherein each R15is independently selected from hydrogen and C1-6 alkyl.

[0362] 104. A molecular glue degrader compound of any one of embodiments 7-103, wherein R15is hydrogen.

[0363] 105. A molecular glue degrader compound of any one of embodiments 7-104, wherein R15aand R15bare independently selected from hydrogen, -OH, halogen, C1-6 alkyl, and C1-6 haloalkyl.

[0364] 106. A molecular glue degrader compound of any one of embodiments 7-105, wherein R15aand R15bare independently selected from hydrogen and Ci-6 alkyl.

[0365] 107. A molecular glue degrader compound of any one of embodiments 7-106, wherein R15aand R15bare both hydrogen. 108. A molecular glue degrader compound of any one of embodiments 7-107, wherein RBis hydrogen.

[0366] 109. A molecular glue degrader compound of any one of embodiments 7-107, wherein RBis Ci-6 alkyl.

[0367] 110. A molecular glue degrader compound of any one of embodiments 7-109, wherein RBis - CH3.

[0368] 111. A molecular glue degrader compound of any one of embodiments 7-110, wherein m is 0 or 1.

[0369] 112. A molecular glue degrader compound of any one of embodiments 7-111, wherein m is 1.

[0370] 113. A molecular glue degrader compound of any one of embodiments 7-112, wherein n is 0 or 1.

[0371] 114. A molecular glue degrader compound of any one of embodiments 7-113, wherein n is 0.

[0372] 115. A molecular glue degrader compound of any one of embodiments 7-114, wherein p is 0,

[0373] 1, or 2.

[0374] 116. A molecular glue degrader compound of any one of embodiments 7-115, wherein p is 1 or 2.

[0375] 117. A molecular glue degrader compound of any one of embodiments 7-116, wherein p is 1.

[0376] 118. A molecular glue degrader compound of any one of embodiments 7-117, wherein p is 2. 119. A molecular glue degrader compound of any one of embodiments 7-118, wherein R1and R2together with the atoms to which they are attached form a 6-membered heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9; and L2is absent or -C(O)-CH2-O-*, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I).

[0377] 120. A molecular glue degrader compound of any one of embodiments 7-119, wherein L1is - C2-5 cycloalkyl-NH-* or -C2-5 cycloalkyl-NH-C(O)-CH2-O-*, wherein each cycloalkyl are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I).

[0378] 121. A molecular glue degrader compound of any one of embodiments 7-120, wherein L1is - C4 cycloalkyl-NH-* or -C4 cycloalkyl-NH-C(O)-CH2-O-*, wherein each cycloalkyl are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I).

[0379] 122. A molecular glue degrader compound of any one of embodiments 7-121, wherein R6aand R6b, together with the atoms to which they are attached, form an oxo group; m is 1; and n is 0.

[0380] 123. A molecular glue degrader compound of any one of embodiments 7-122, wherein X is O; and n is 0.

[0381] 124. The molecular glue degrader compound of any one of embodiments 7-123, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Il-a): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0382] X is O or S; Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3 - to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl, optionally substituted with one or more R7;

[0383] — L4Target Ligand

[0384] R1is

[0385] L1is a linker selected from the group of alkyl, heteroalkyl, C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R13, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I);

[0386] Target Ligand comprises a moiety capable of binding to a target protein;

[0387] R2is selected from the group consisting of hydrogen and Ci-6 alkyl; or

[0388] R1and R2together with the atoms to which they are attached form a 5- to 10-membered heteroaryl or a 3 - to 12-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9;

[0389] R4and R3are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;

[0390] R7are each independently selected from the group consisting of -OH, halogen, C1-6 alkyl, Ci-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl;

[0391] — L Target Ligand

[0392] R8is

[0393] L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R15is independently selected from hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci-6 hydroxyalkyl, C1-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0394] RBis hydrogen or Ci-6 alkyl; and p is 0, 1, 2, 3, or 4.

[0395] 125. The molecular glue degrader compound of any one of embodiments 7-123, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Il-b): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0396] X is O or S;

[0397] Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3- to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl;

[0398] L2is a linker substituted with 0-4 occurrences of R9;

[0399] Target Ligand comprises a moiety capable of binding to a target protein;

[0400] R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;

[0401] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0402] R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R are each independently selected from the group consisting of hydrogen, -OH, halogen, - CN, Ci-6 alkyl, and Ci-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0403] R6aand R6h, together with the atoms to which they are attached, form an oxo group; each

[0404] R7is independently selected from the group consisting of -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci-6 haloalkyl, and C1-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3- cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0405] 126. A molecular glue degrader compound of embodiment 125, wherein each R10is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, and Ci-6 haloalkyl.

[0406] 127. A molecular glue degrader compound of any one of embodiments 125-126, wherein each R10is independently selected from hydrogen and Ci-6 alkyl.

[0407] 128. A molecular glue degrader compound of any one of embodiments 125-127, wherein R10is hydrogen.

[0408] 129. The molecular glue degrader compound of any one of embodiments 7-123, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (II-c): (II-c), or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0409] X is O or S;

[0410] Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3 - to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl;

[0411] L2is a linker substituted with 0-4 occurrences of R9;

[0412] Target Ligand comprises a moiety capable of binding to a target protein;

[0413] R2aand R2bare each independently hydrogen, Ci -6 alkyl, and C3-8 cycloalkyl;

[0414] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0415] R3aand R3b, together with the atoms to which they are attached, form an oxo group;

[0416] R4and R?are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;

[0417] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0418] R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0419] 130. The molecular glue degrader compound of any one of embodiments 7-129, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Il-d): acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0420] X is O or S;

[0421] Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3- to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl, optionally substituted with one or more R7;

[0422] Target Ligand comprises a moiety capable of binding to a target protein;

[0423] R2aand R2bare each independently hydrogen, C1-6 alkyl, and C3-8 cycloalkyl;

[0424] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0425] R3aand R3b, together with the atoms to which they are attached, form an oxo group;

[0426] R4and R are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;

[0427] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0428] R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0429] 131. The molecular glue degrader compound of any one of embodiments 7-130, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Il-e): acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0430] X is O or S;

[0431] Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3- to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl, optionally substituted with one or more R7;

[0432] Target Ligand comprises a moiety capable of binding to a target protein;

[0433] R2aand R2bare each independently hydrogen, C1-6 alkyl, and C3-8 cycloalkyl;

[0434] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0435] R3aand R3b, together with the atoms to which they are attached, form an oxo group;

[0436] R4and R are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;

[0437] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0438] R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0439] 132. The molecular glue degrader compound of any one of embodiments 7-131, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Il-f): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0440] X is O or S;

[0441] Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3 - to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl, optionally substituted with one or more R7;

[0442] R2aand R2bare each independently hydrogen, C1-6 alkyl, and C3-8 cycloalkyl;

[0443] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0444] R3aand R3b, together with the atoms to which they are attached, form an oxo group;

[0445] R4and R?are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;

[0446] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0447] R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0448] R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl;

[0449] R12is selected from the group consisting of hydrogen, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, and Ci-6 haloalkyl;

[0450] R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0451] R15aand R15bare each independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0452] RBis hydrogen or Ci-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, 4, or 5; and q is 0, 1, 2, 3, or 4.

[0453] 133. The molecular glue degrader compound of any one of embodiments 7-132, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Il-g): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0454] X is O or S;

[0455] R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;

[0456] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R3aand R3b, together with the atoms to which they are attached, form an oxo group;

[0457] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl;

[0458] R6aand R6hare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0459] R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0460] R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl;

[0461] R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl;

[0462] R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0463] R15aand R15bare each independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, 4, or 5; and q is 0, 1, 2, 3, or 4.

[0464] 134. The molecular glue degrader compound of any one of embodiments 7-133, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Il-h): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0465] R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;

[0466] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0467] R3aand R3b, together with the atoms to which they are attached, form an oxo group;

[0468] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl; each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3- cycloalkyl;

[0469] R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and Ci-6 haloalkoxyl;

[0470] R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl;

[0471] R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0472] R15aand R15bare each independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3- cycloalkyl; n is 0, 1, or 2; p is 0, 1, 2, 3, 4, or 5; and q is 0, 1, 2, 3, or 4.

[0473] 135. The molecular glue degrader compound of any one of embodiments 7-134, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Il-i): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein X1and X2are each independently O or S; Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10-membered heteroaryl, a 3- to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl; Target Ligand comprises a moiety capable of binding to a target protein; R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, C1-6 alkyl, and C1-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of- OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl; R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; o is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0474] 136. A molecular glue degrader compound of embodiment 135, wherein o is 0 or 1.

[0475] 137. A molecular glue degrader compound of any one of embodiments 135-136, wherein 0 is 0. 138. A molecular glue degrader compound of any one of embodiments 135-137, wherein o is 1.

[0476] 139. The molecular glue degrader compound of any one of embodiments 7-138, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Il-j): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein X is O or S; Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3 - to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl, optionally substituted with one or more R7; L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene-*, -C(0)-Co-4 heteroalkylene-*, -C(O)- Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); Target Ligand comprises a moiety capable of binding to a target protein; R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R3are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, C1-6 alkyl, and Ci-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of- OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; each R15is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1 , 2, 3, 4, or 5.

[0477] 140. The molecular glue degrader compound of any one of embodiments 7-139, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Il-k): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein X1and X2are each independently O or S; Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10-membered heteroaryl, a 3- to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl; Target Ligand comprises a moiety capable of binding to a target protein; R2aand R2bare each independently hydrogen, C1-6 alkyl, and C3-8 cycloalkyl; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of- OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; o is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5. 141 . The molecular glue degrader compound of any one of embodiments 7-139, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (II-l): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: X1and X2are each independently O or S; Target Ligand comprises a moiety capable of binding to a target protein; R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, C1-6 alkyl, and C1-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of- OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl; R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or R8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; o is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0478] 142. The molecular glue degrader compound of any one of embodiments 7-139, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (ILm): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0479] X1and X2are each independently O or S;

[0480] Target Ligand comprises a moiety capable of binding to a target protein;

[0481] R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;

[0482] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0483] R3aand R3b, together with the atoms to which they are attached, form an oxo group;

[0484] R4and R?are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;

[0485] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0486] R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl;

[0487] R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0488] R8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2;

[0489] 0 is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5. 143. The molecular glue degrader compound of any one of embodiments 7-139, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Il-n): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0490] R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;

[0491] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl; each R7and R11is independently selected from the group consisting of -OH, halogen, Ci- 6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl;

[0492] R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0493] R8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10and R13is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl;

[0494] R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; m is 0, 1, or 2; n is 0, 1, or 2;

[0495] 0 is 0, 1, or 2; p is 0, 1, 2, 3, 4, or 5; and q is 0, 1, 2, 3, or 4.

[0496] 144. The molecular glue degrader compound of any one of embodiments 7-139, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (II-o): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0497] R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;

[0498] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl; each R7and R11is independently selected from the group consisting of -OH, halogen, Ci- 6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl;

[0499] R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0500] R8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10and R13is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl;

[0501] R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; o is 0, 1, or 2; p is 0, 1, 2, 3, 4, or 5; and q is 0, 1, 2, 3, or 4.

[0502] 145. The molecular glue degrader compound of any one of embodiments 7-139, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (II-p): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0503] R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;

[0504] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl; each R7and R11is independently selected from the group consisting of -OH, halogen, Ci. 6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl;

[0505] R7ais selected from the group consisting of hydrogen, C1-6 alkyl, or C3-8 cycloalkyl;

[0506] R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0507] R8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10and R13is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl;

[0508] R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; o is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0509] 146. The molecular glue degrader compound of any one of embodiments 7-145, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Il-q): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0510] R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;

[0511] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl; each R7and R11is independently selected from the group consisting of -OH, halogen, Ci. 6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl;

[0512] R7ais selected from the group consisting of hydrogen, C1-6 alkyl, or C3-8 cycloalkyl;

[0513] R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0514] R8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10and R13is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl;

[0515] R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; o is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0516] 147. The molecular glue degrader compound of any one of embodiments 7-146, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Il-r): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0517] X is O or S;

[0518] Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3 - to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl, optionally substituted with one or more R7;

[0519] L1is a linker selected from the group of alkyl, heteroalkyl, C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I);

[0520] R2is selected from the group consisting of hydrogen and Ci-6 alkyl;

[0521] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl;

[0522] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl;

[0523] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0524] R6aand R6b, together with the atoms to which they are attached, form an oxo group;

[0525] R7is selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl;

[0526] R10is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0527] R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, and Ci-6 haloalkyl;

[0528] R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0529] 148. The molecular glue degrader compound of any one of embodiments 7-122, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (III): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0530] X is O or S;

[0531] Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7;

[0532] Target Ligand comprises a moiety capable of binding to a target protein;

[0533] L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I);

[0534] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0535] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0536] R6aand R6h, together with the atoms to which they are attached, form an oxo group;

[0537] R7are each independently selected from the group consisting of -OH, halogen, C1-6 alkyl, Ci-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3- cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R1?is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0538] RBis hydrogen or Ci-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, or 4.

[0539] 149. The molecular glue degrader compound of any one of embodiments 148, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Ill-a): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: X is O or S; Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7;

[0540] L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I);

[0541] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0542] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;

[0543] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0544] R6aand R6b, together with the atoms to which they are attached, form an oxo group;

[0545] R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring;

[0546] R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl;

[0547] R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl;

[0548] R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; each R1?is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0549] RBis hydrogen or C1-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0550] 150. The molecular glue degrader compound of any one of embodiments 148-149, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Ill-b): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0551] X is O or S;

[0552] Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally

[0553] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl;

[0554] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl;

[0555] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0556] R6aand R6b, together with the atoms to which they are attached, form an oxo group;

[0557] R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3- cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring;

[0558] R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl;

[0559] R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, and Ci-6 haloalkyl;

[0560] R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0561] R15aand R15bare each independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0562] 151. The molecular glue degrader compound of any one of embodiments 148-150, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (III-c): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0563] X is O or S;

[0564] Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0565] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;

[0566] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0567] R6aand R6b, together with the atoms to which they are attached, form an oxo group;

[0568] R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring;

[0569] R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl;

[0570] R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl;

[0571] R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4. 152. The molecular glue degrader compound of any one of embodiments 148-151, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (IILd): (IH-d), or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0572] X is O or S;

[0573] L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I);

[0574] Target Ligand comprises a moiety capable of binding to a target protein;

[0575] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0576] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;

[0577] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0578] R6aand R6b, together with the atoms to which they are attached, form an oxo group;

[0579] R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R15is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0580] RBis hydrogen or C1-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0581] 153. The molecular glue degrader compound of any one of embodiments 148-152, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Ill-e): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0582] X is O or S;

[0583] L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I);

[0584] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl;

[0585] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, C1-6 alkyl, and C1-6 haloalkyl;

[0586] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or R6aand R6b, together with the atoms to which they are attached, form an oxo group;

[0587] R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring;

[0588] R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl;

[0589] R12is selected from the group consisting of hydrogen, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, and Ci-6 haloalkyl;

[0590] R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; each R15is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0591] RBis hydrogen or Ci-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0592] 154. The molecular glue degrader compound of any one of embodiments 148-153, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Ill-f): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0593] X is O or S;

[0594] L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I);

[0595] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0596] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;

[0597] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0598] R6aand R6b, together with the atoms to which they are attached, form an oxo group;

[0599] R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl;

[0600] R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl;

[0601] R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0602] R15aand R15bare each independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0603] RBis hydrogen or Ci-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0604] 155. The molecular glue degrader compound of any one of embodiments 148-154, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Ill-g): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0605] Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3 - to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl, optionally substituted with one or more R7;

[0606] L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0607] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;

[0608] R7are each independently selected from the group consisting of -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring;

[0609] R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl;

[0610] R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl;

[0611] R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; each R15is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0612] RBis hydrogen or Ci-6 alkyl; n is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

[0613] 156. The molecular glue degrader compound of any one of embodiments 148-155, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Ill-h): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein Ring B is a 5- to 10-membered heteroaryl or a 3- to 12-membered heterocycloalkyl, and each of the Ring A, L2, R4, R5, R6a, R6b, R7, R9, m, p, and q are as defined for Formula (II).

[0614] 157. The molecular glue degrader compound of any one of embodiments 1-156, wherein the molecular glue degrader compound or an intermediate thereof is selected from a compound in Table 1 or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof.

[0615] 158. The molecular glue degrader compound of any one of embodiments 1-157, wherein the molecular glue degrader compound is selected from Compound 132 and 133 or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof.

[0616] 159. The molecular glue degrader compound of any one of embodiments 1-158, wherein the molecular glue degrader compound is selected from Compound 289 and 290 or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof.

[0617] 160. The molecular glue degrader compound of any one of embodiments 1-159, wherein the molecular glue degrader compound is capable of modulating one or more of:

[0618] (i) reducing the stability of the target protein;

[0619] (ii) reducing the half-life of the target protein;

[0620] (iii) facilitating trafficking of the target protein to the proteasome;

[0621] (iv) increasing the level of ubiquitination of the target protein; and

[0622] (v) increasing the rate of degradation (e.g., proteasomal degradation) of the target protein.

[0623] 161. The molecular glue degrader compound of embodiment 160, comprising (i). 162. The molecular glue degrader compound of any one of embodiments 160-161, comprising

[0624] (ii).

[0625] 163. The molecular glue degrader compound of any one of embodiments 160-162, comprising

[0626] (iii).

[0627] 164. The molecular glue degrader compound of any one of embodiments 160-163, comprising

[0628] (iv).

[0629] 165. The molecular glue degrader compound of any one of embodiments 160-164, comprising

[0630] (v).

[0631] 166. The molecular glue degrader compound of any one of embodiments 160-165, comprising each of (i)-(v).

[0632] 167. The molecular glue degrader compound of any one of embodiments 1-166, wherein the binding of the molecular glue degrader compound to a RING E3 ubiquitin ligase does not substantially inhibit the activity of the RING E3 ubiquitin ligase.

[0633] 168. The molecular glue degrader compound of any one of embodiments 1-167, wherein the molecular glue degrader compound binds to a site other than a catalytic site within a RING E3 ubiquitin ligase.

[0634] 169. The molecular glue degrader compound of any one of embodiments 1-168, wherein the molecular glue degrader compound binds to an allosteric site within a RING E3 ubiquitin ligase.

[0635] 170. The molecular glue degrader compound of any one of embodiments 1-169, wherein the molecular glue degrader compound binds to a cysteine amino acid residue within the RING E3 ubiquitin ligase. 171. The molecular glue degrader compound of any one of embodiments 1-170, wherein the molecular glue degrader compound preferentially binds to an allosteric amino acid residue (e.g., an allosteric amino acid residue) over a catalytic amino acid residue (e.g., a catalytic cysteine amino acid residue).

[0636] 172. The molecular glue degrader compound of any one of embodiments 1-171, wherein molecular glue degrader compound does not substantially bind to a cysteine amino acid residue in the catalytic site of a RING E3 ubiquitin ligase (e.g., a catalytic cysteine).

[0637] 173. A pharmaceutical composition comprising a molecular glue degrader compound of any one of embodiments 1-172, and one or more pharmaceutically acceptable carriers.

[0638] 174. A method of providing a molecular glue degrader compound to a subject, wherein the molecular glue degrader compound has the structure of Formula (II): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0639] X is O or S;

[0640] Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7;

[0641] — 1 Target Ligand

[0642] R1is

[0643] L1is a linker selected from the group of alkyl, heteroalkyl, C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I);

[0644] Target Ligand comprises a moiety capable of binding to a target protein;

[0645] R2is selected from the group consisting of hydrogen and Ci-6 alkyl; or R1and R2together with the atoms to which they are attached form a 5- to 10-membered heteroaryl or a 3 - to 12-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9;

[0646] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0647] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;

[0648] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0649] R6aand R6b, together with the atoms to which they are attached, form an oxo group;

[0650] R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl;

[0651] — L Target Ligand

[0652] R8is

[0653] L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R15is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; RBis hydrogen or Ci-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, or 4.

[0654] 175. A method of providing a molecular glue degrader compound to a subject, wherein the molecular glue degrader compound has the structure of Formula (ILb): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0655] X is O or S;

[0656] Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3 - to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl;

[0657] L2is a linker substituted with 0-4 occurrences of R9;

[0658] Target Ligand comprises a moiety capable of binding to a target protein;

[0659] R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;

[0660] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0661] R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, - CN, Ci-6 alkyl, and Ci-6 haloalkyl;

[0662] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0663] R6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0664] 176. A method of treating a disease, disorder, or condition in a subject, wherein the method comprises administering to the subject a molecular glue degrader compound of Formula (II): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0665] X is O or S;

[0666] Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7;

[0667] — L1Target Ligand

[0668] R1is

[0669] L1is a linker selected from the group of alkyl, heteroalkyl, C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I);

[0670] Target Ligand comprises a moiety capable of binding to a target protein;

[0671] R2is selected from the group consisting of hydrogen and Ci-6 alkyl; or

[0672] R1and R2together with the atoms to which they are attached form a 5- to 10-membered heteroaryl or a 3 - to 12-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9;

[0673] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0674] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;

[0675] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0676] R6aand R6b, together with the atoms to which they are attached, form an oxo group;

[0677] R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl;

[0678] — I Target Ligand

[0679] R8is

[0680] L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R15is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0681] RBis hydrogen or C1-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, or 4.

[0682] 177. A method of treating a disease, disorder, or condition in a subject, wherein the method comprises administering to the subject a molecular glue degrader compound of Formula (Il-a): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0683] X is O or S;

[0684] Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3- to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl;

[0685] L2is a linker substituted with 0-4 occurrences of R9;

[0686] Target Ligand comprises a moiety capable of binding to a target protein;

[0687] R2aand R2bare each independently hydrogen, C1-6 alkyl, and C3-8 cycloalkyl;

[0688] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0689] R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R are each independently selected from the group consisting of hydrogen, -OH, halogen, - CN, C1-6 alkyl, and Ci-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0690] R6aand R6h, together with the atoms to which they are attached, form an oxo group; each

[0691] R7is independently selected from the group consisting of -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci-6 haloalkyl, and C1-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3- cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0692] 178. The method of any one of embodiments 176-177, wherein the disease, disorder, or condition is cancer.

[0693] 179. The method of any one of embodiments 176-178, wherein the subject is a mammal (e g., a human).

[0694] 180. A method of ubiquitinating a target protein comprising contacting a cell or sample with a molecular glue compound of Formula (II): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0695] X is O or S;

[0696] Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7;

[0697] — L1- Target Ligand

[0698] R1is

[0699] L1is a linker selected from the group of alkyl, heteroalkyl, C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R'y wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I);

[0700] Target Ligand comprises a moiety capable of binding to a target protein;

[0701] R2is selected from the group consisting of hydrogen and Ci-6 alkyl; or

[0702] R1and R2together with the atoms to which they are attached form a 5- to 10-membered heteroaryl or a 3 - to 12-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9;

[0703] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl;

[0704] R4and R are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl;

[0705] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0706] R6aand R6b, together with the atoms to which they are attached, form an oxo group; R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl;

[0707] — I Target Ligand

[0708] R8is

[0709] L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R15is independently selected from hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0710] RBis hydrogen or C1-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, or 4.

[0711] 181. A method of ubiquitinating a target protein comprising contacting a cell or sample with a molecular glue compound of Formula (Il-a): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: X is O or S;

[0712] Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3 - to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl;

[0713] L2is a linker substituted with 0-4 occurrences of R9;

[0714] Target Ligand comprises a moiety capable of binding to a target protein;

[0715] R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;

[0716] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0717] R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R?are each independently selected from the group consisting of hydrogen, -OH, halogen, - CN, Ci-6 alkyl, and Ci-6 haloalkyl;

[0718] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0719] R6aand R6b, together with the atoms to which they are attached, form an oxo group; each

[0720] R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0721] 182. A method of degrading a target protein comprising contacting a cell or sample with a molecular glue compound of Formula (II): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0722] X is O or S;

[0723] Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7;

[0724] Target Ligand

[0725] R1is

[0726] L1is a linker selected from the group of alkyl, heteroalkyl, C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I);

[0727] Target Ligand comprises a moiety capable of binding to a target protein;

[0728] R2is selected from the group consisting of hydrogen and Ci-6 alkyl; or

[0729] R1and R2together with the atoms to which they are attached form a 5- to 10-membered heteroaryl or a 3 - to 12-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9;

[0730] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl;

[0731] R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl; R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0732] R6aand R6h, together with the atoms to which they are attached, form an oxo group;

[0733] R7are each independently selected from the group consisting of -OH, halogen, C1-6 alkyl, Ci-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl;

[0734] — I Target Ligand

[0735] R8is

[0736] L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R15is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;

[0737] RBis hydrogen or Ci-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, or 4.

[0738] 183. A method of degrading a target protein comprising contacting a cell or sample with a molecular glue compound of Formula (ILa): pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

[0739] X is O or S;

[0740] Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3 - to 12-membered cycloalkyl, and a 3 - to 12-membered heterocycloalkyl;

[0741] L2is a linker substituted with 0-4 occurrences of R9;

[0742] Target Ligand comprises a moiety capable of binding to a target protein;

[0743] R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;

[0744] R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0745] R3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R3are each independently selected from the group consisting of hydrogen, -OH, halogen, - CN, C1-6 alkyl, and Ci-6 haloalkyl;

[0746] R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; or

[0747] R6aand R6b, together with the atoms to which they are attached, form an oxo group; each

[0748] R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3- cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

[0749] 184. The method of embodiment 183, wherein the target protein selected from a tyrosine kinase, a serine / threonine kinase, a bromodomain-containing protein, an epigenetic protein, and a misfolded protein.

[0750] 185. The method of any one of embodiments 183-184, wherein the target protein is selected from AR, BCL-2 / BCL, BCL-XL, BCR-ABL, BRD2, BRD3, BRD4, BRD9, BRDT, BTK, BUB1, BUB1B, c-ABL, CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11B, CDK12, CDK13, CDK14, CDK15, CDK16, CDK17, CDK18, CDK19, CDK20, CHEK1, CKS1B, CKS2, CSNK1A1, CSNK1E, CTNNB1, DSTYK, EEF2K, estrogen receptor (ER), ETNK1, FASTKD5, HRAS, ITPKB, KRAS, LRKK2, MAPKAPK2 (MK2), MARK2, MAP3K2, MELK, MYC, MYCN, NEK6, NRAS, PANK2, PANK3, PDE5, PHKA1, PHKA2, PKN2, PLK1, PTK6, RIOK2, SKP2, SMARCA2, SMARCA4, STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6, TK1, TTK, and UCK2.

[0751] 186. The method of any one of embodiments 183-185, wherein the target protein is selected from AR-V7, Bcl-2 / Bcl, BCR-ABL, BRD4, BTK, BUB1, BUB1B, c-ABL, CDK4, CDK1 IB, CHEK1, CKS1B, CKS2, CSNK1A1, CSNK1E, DSTYK, EEF2K, ETNK1, FASTKD5, ITPKB, KRAS G12D, LRKK2, MARK2, MAP3K2, MELK, NEK6, PANK2, PANK3, PDE5, PHKA1, PHKA2, PKN2, PLK1, RIOK2, SKP2, SMARCA2, TK1, TTK, and UCK2.

[0752] 187. The method of any one of embodiments 183-186, wherein the target protein is selected from CDK4, CDK6, BRD4, PDE5, BCR-ABL, c-ABL, AR, AR-V7, BTK, LRKK2, or

[0753] SMARCA2. EXAMPLES

[0754] The disclosure is further illustrated by the following examples and synthesis schemes, which are not to be construed as limiting this disclosure in scope or spirit to the specific procedures herein described. It is to be understood that the examples are provided to illustrate certain embodiments and that no limitation to the scope of the disclosure is intended thereby. It is to be further understood that resort may be had to various other embodiments, modifications, and equivalents thereof which may suggest themselves to those skilled in the art without departing from the spirit of the present disclosure and / or scope of the appended claims.

[0755] Compounds of the present disclosure may be prepared by methods known in the art of organic synthesis. In all of the methods it is understood that protecting groups for sensitive or reactive groups may be employed where necessary in accordance with general principles of chemistry. Protecting groups are manipulated according to standard methods of organic synthesis (T.W. Green and P G M. Wuts (1999) Protective Groups in Organic Synthesis, 3rd edition, John Wiley & Sons). These groups are removed at a convenient stage of the compound synthesis using methods that are readily apparent to those skilled in the art.

[0756] Synthetic Methods and Characterization

[0757] All chemical reactions were carried out under a nitrogen atmosphere with dry solvents under anhydrous conditions, unless otherwise noted. Reagents were purchased at the highest commercial quality and used without further purification, unless otherwise stated. Reactions were stirred magnetically and monitored by thin layer chromatography (TLC) carried out on Merck glass silica gel plates (60 F254) using UV light as a visualizing agent and iodine and / or phosphomolybdic acid stain as developing agents. Solvents were removed in vacuo using either a Buchi R-300 Rotavapor (equipped with an 1-300 Pro Interface, B-300 Base Heating Bath, Welch 2037B-01 DryFast pump, and VWR AD15R-40-V1 IB Circulating Bath). Solvents for silica gel chromatography were used as supplied by Sigma-Aldrich. Automated flash chromatography was performed on a Biotage Isolera instrument, equipped with ...

Claims

CLAIMS1. A molecular glue degrader compound of Formula (I):Target Ligand - 1 Bridge ! - RING E3 Ligase Binder' - - - - - 'v- ' ' - - - ' (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein: (i) the Target Ligand is capable of binding to a target protein;(ii) Bridge is absent or a linker; and(iii) the RING E3 Ligase Binder is capable of binding to a RING E3 ubiquitin ligase (e.g., RNF126 or BCA2).

2. The molecular glue degrader compound of claim 1, wherein the target protein selected from a tyrosine kinase, a serine / threonine kinase, a bromodomain-containing protein, an epigenetic protein, and a misfolded protein.

3. The molecular glue degrader compound of any one of claims 1-2, wherein the target protein is selected from AR, BCL-2 / BCL, BCL-XL, BCR-ABL, BRD2, BRD3, BRD4, BRD9, BRDT, BTK, BUB1, BUB IB, c-ABL, CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11B, CDK12, CDK13, CDK14, CDK15, CDK16, CDK17, CDK18, CDK19, CDK20, CHEK1, CKS1B, CKS2, CSNK1A1, CSNK1E, CTNNB1, DSTYK, EEF2K, estrogen receptor (ER), ETNK1, FASTKD5, HRAS, ITPKB, KRAS, LRKK2, MAPKAPK2 (MK2), MARK2, MAP3K2, MELK, MYC, MYCN, NEK6, NRAS, PANK2, PANK3, PDE5, PHKA1, PHKA2, PKN2, PLK1, PTK6, RIOK2, SKP2, SMARCA2, SMARCA4, STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6, TK1, TTK, and UCK2.

4. The molecular glue degrader compound of any one of claims 1-3, wherein the target protein is selected from AR-V7, Bcl-2 / Bcl, BCR-ABL, BRD4, BTK, BUB1, BUB IB, c-ABL, CDK4, CDK11B, CHEK1, CKS1B, CKS2, CSNK1A1, CSNK1E, DSTYK, EEF2K, ETNK1, FASTKD5, ITPKB, KRAS G12D, LRKK2, MARK2, MAP3K2, MELK, NEK6, PANK2, PANK3, PDE5, PHKA1, PHKA2, PKN2, PLK1, RI0K2, SKP2, SMARCA2, TK1, TTK, and UCK2.

5. The molecular glue degrader compound of any one of claims 1-4, wherein the target protein is selected from CDK4, CDK6, BRD4, PDE5, BCR-ABL, c-ABL, AR, AR-V7, BTK, LRKK2, or SMARCA2.

6. The molecular glue degrader compound of any one of claims 1-5, wherein the target protein is AR or AR-V7.

7. The molecular glue degrader compound of any one of claims 1-6, wherein the molecular glue degrader compound has the structure of Formula (II):pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:X is O or S;Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7;— L1Target LigandR1isL1is a linker selected from the group of alkyl, heteroalkyl, C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I);Target Ligand comprises a moiety capable of binding to a target protein;R2is selected from the group consisting of hydrogen and Ci-6 alkyl; orR1and R2together with the atoms to which they are attached form a 5- to 10-membered heteroaryl or a 3 - to 12-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9;R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; orR6aand R6b, together with the atoms to which they are attached, form an oxo group;R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl;— L Target LigandR8isL2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3- cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R1?is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;RBis hydrogen or Ci-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, or 4.

8. A molecular glue degrader compound of claim 7, wherein Ring A is aryl or heteroaryl, each of which is optionally substituted with one or more R7.

9. A molecular glue degrader compound of any one of claims 7-8, wherein Ring A is aryl, optionally substituted with one or more R7.

10. A molecular glue degrader compound of any one of claims 7-9, wherein Ring A is monocyclic or bicyclic aryl, optionally substituted with one or more R7.

11. A molecular glue degrader compound of any one of claims 7-10, wherein Ring A is 6- to 10-membered aryl (e.g., phenyl), optionally substituted with one or more R7.

12. A molecular glue degrader compound of any one of claims 7-11, wherein Ring A is 6- membered aryl (e.g., phenyl), optionally substituted with one or more R7.

13. A molecular glue degrader compound of any one of claims 7-12, wherein Ring A is phenyl, optionally substituted with one or more R7.

14. A molecular glue degrader compound of any one of claims 7-13, wherein Ring A is15. A molecular glue degrader compound of any one of claims 7-14, wherein Ring A is16. A molecular glue degrader compound of any one of claims 7-15, wherein Ring A is selected from17. A molecular glue degrader compound of any one of claims 7-16, wherein X is O.

18. A molecular glue degrader compound of any one of claims 7-17, wherein L1is selected from -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, and -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I).

19. A molecular glue degrader compound of any one of claims 7-18, wherein L1is -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I).

20. A molecular glue degrader compound of any one of claims 7-19, wherein L1is - cyclobutyl-NH-C(O)-CH2-O-*, optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I).

21. A molecular glue degrader compound of any one of claims 7-20, wherein R2is hydrogen or C1-4 alkyl.

22. A molecular glue degrader compound of any one of claims 7-21, wherein R2is hydrogen.

23. A molecular glue degrader compound of any one of claims 7-20, wherein R1and R2together with the atoms to which they are attached form a heteroaryl or a heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9.

24. A molecular glue degrader compound of any one of claims 7-23, wherein R1and R2together with the atoms to which they are attached form a 5- to 10-membered heteroaryl or a 3- to 12-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9.

25. A molecular glue degrader compound of any one of claims 7-24, wherein R1and R2together with the atoms to which they are attached form a monocyclic or bicyclic heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9.

26. A molecular glue degrader compound of any one of claims 7-25, wherein R1and R2together with the atoms to which they are attached form a monocyclic heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9.

27. A molecular glue degrader compound of any one of claims 7-26, wherein R1and R2together with the atoms to which they are attached form a 5- to 8-membered heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9.

28. A molecular glue degrader compound of any one of claims 7-27, wherein R1and R2together with the atoms to which they are attached form a 6-membered heterocycloalkyl (e.g. piperazinyl), substituted with one R8, and optionally substituted with 1-4 occurrences of R9.

29. A molecular glue degrader compound of any one of claims 7-28, wherein R1and R2together with the atoms to which they are attached form a heterocycloalkyl ring selected from:

30. A molecular glue degrader compound of any one of claims 7-29, wherein R1and R2together with the atoms to which they are attached form31. A molecular glue degrader compound of any one of claims 7-30, wherein L2is absent.

32. A molecular glue degrader compound of any one of claims 7-30, wherein L2is selected from -C(0)-Co-4 heteroalkylene-* and -C(0)-Co-4 alkylene-O-*, wherein each heteroalkylene and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I).

33. A molecular glue degrader compound of any one of claims 7-32, wherein L2is absent or - C(0)-Co-4 alkylene-O-*, wherein the alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I).

34. A molecular glue degrader compound of any one of claims 7-33, wherein L2is -C(O)- C(R15a)(R15b)-O-*, wherein R15aan R15bare independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3.8 cycloalkyl; and wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I).

35. A molecular glue degrader compound of any one of claims 7-34, wherein R13aand R15bare independently selected from hydrogen and Ci-6 alkyl.

36. A molecular glue degrader compound of any one of claims 7-35, wherein R13aand R15bare both hydrogen.

37. A molecular glue degrader compound of any one of claims 7-36, wherein the TargetLigand i, wherein R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; R13is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3.8 cycloalkyl; and q is 0, 1, 2, 3, or 4.

38. A molecular glue degrader compound of any one of claims 7-37, wherein R11is selected from -OH and Ci-6 alkyl.

39. A molecular glue degrader compound of any one of claims 7-38, wherein R12is hydrogen or Ci-6 alkyl.

40. A molecular glue degrader compound of any one of claims 7-39, wherein R13is hydrogen.

41. A molecular glue degrader compound of any one of claims 7-40, wherein q is 0 or 1.

42. A molecular glue degrader compound of any one of claims 7-41, wherein the TargetLigand i43. A molecular glue degrader compound of any one of claims 7-42, wherein R3aand R3bare each independently selected from hydrogen and Ci-6 alkyl.

44. A molecular glue degrader compound of any one of claims 7-43, wherein R3aand R3bare each independently hydrogen.

45. A molecular glue degrader compound of any one of claims 7-44, wherein R4and R5are each independently selected from hydrogen and Ci-6 alkyl.

46. A molecular glue degrader compound of any one of claims 7-45, wherein R4and R5are each independently hydrogen.

47. A molecular glue degrader compound of any one of claims 7-46, wherein R6aand R6bare each independently selected from hydrogen, -OH, halogen, and Ci-6 alkyl.

48. A molecular glue degrader compound of any one of claims 7-47, wherein R6aand R6b, together with the atoms to which they are attached, form an oxo group.

49. A molecular glue degrader compound of any one of claims 7-48, wherein each R7is independently selected from halogen, Ci-6 alkoxyl, and Ci-6 haloalkyl.

50. A molecular glue degrader compound of any one of claims 7-49, wherein each R7is independently selected from halogen and Ci-6 alkoxyl.

51. A molecular glue degrader compound of any one of claims 7-50, wherein R7is -OCH3.

52. A molecular glue degrader compound of any one of claims 7-51, wherein each R9is independently selected from the group consisting of -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl.

53. A molecular glue degrader compound of any one of claims 7-52, wherein R9is Ci-6 alkyl (e g., methyl, ethyl, propyl).

54. A molecular glue degrader compound of any one of claims 7-53, wherein each R15is independently selected from hydrogen and Ci-6 alkyl.

55. A molecular glue degrader compound of any one of claims 7-54, wherein R13is hydrogen.

56. A molecular glue degrader compound of any one of claims 7-55, wherein RBis hydrogen.

57. A molecular glue degrader compound of any one of claims 7-56, wherein m is 1.

58. A molecular glue degrader compound of any one of claims 7-57, wherein n is 0.

59. A molecular glue degrader compound of any one of claims 7-58, wherein p is 1 or 2.

60. A molecular glue degrader compound of any one of claims 7-59, wherein R1and R2together with the atoms to which they are attached form a 6-membered heterocycloalkyl, substituted with one R8, and optionally substituted with 1-4 occurrences of R9; and L2is absent or -C(O)-CH2-O-*, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I).

61. A molecular glue degrader compound of any one of claims 7-60, wherein L1is -C2-5 cycloalkyl-NH-* or -C2-5 cycloalkyl-NH-C(O)-CH2-O-*, wherein each cycloalkyl are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I).

62. A molecular glue degrader compound of any one of claims 7-61, wherein L1is -C4 cycloalkyl-NH-* or -C4 cycloalkyl-NH-C(O)-CH2-O-*, wherein each cycloalkyl are optionallysubstituted with one or more R1?, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I).

63. A molecular glue degrader compound of any one of claims 7-62, wherein R6aand R6b, together with the atoms to which they are attached, form an oxo group; m is 1; and n is 0.

64. A molecular glue degrader compound of any one of claims 7-63, wherein X is O; and n is 0.

65. The molecular glue degrader compound of any one of claims 7-64, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Il-a):pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: , X, Ring A, R1, R2, R4, R5, R7, p, and subvariables within are as defined in Formula (II).

66. The molecular glue degrader compound of any one of claims 7-65, wherein the molecular glue degrader compound has the structure of Formula (ILb):pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:X is O or S;Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3 - to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl;L2is a linker substituted with 0-4 occurrences of R9;Target Ligand comprises a moiety capable of binding to a target protein;R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;R3aand R3hare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; orR3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, - CN, C1-6 alkyl, and Ci-6 haloalkyl;R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; orR6aand R6b, together with the atoms to which they are attached, form an oxo group; eachR7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

67. A molecular glue degrader compound of claim 66, wherein each R10is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, and Ci-6 haloalkyl.

68. A molecular glue degrader compound of any one of claims 66-67, wherein R10is hydrogen.

69. The molecular glue degrader compound of any one of claims 7-68, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Il-d):pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; and wherein X, Ring A, Target Ligand, R3a, R3b, R4, R5, R6a, R6b, R7, m, n, p, and subvariables therein are as defined in Formula (II).

70. The molecular glue degrader compound of any one of claims 7-69, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (ILe):acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; and wherein X, Ring A, Target Ligand, R3a, R3b, R4, R5, R6a, R6b, R7, m, n, p, and subvariables therein are as defined in Formula (II).71 . The molecular glue degrader compound of any one of claims 7-70, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Il-g):pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; R11is selected from the group consisting of -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl; R12is selected from the group consisting of hydrogen, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci-6 hydroxyalkyl, and C1-6 haloalkyl; R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; R15aand R15bare each independently selected from hydrogen, - OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3- 8 cycloalkyl; and wherein X, R3a, R3b, R4, R5, R6a, R6b, R7, m, n, p, q, and subvariables therein are as defined in Formula (II).

72. The molecular glue degrader compound of any one of claims 1-71, having a structure of Formula (Il-i) :pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:X1and X2are each independently O or S;Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3 - to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl;Target Ligand comprises a moiety capable of binding to a target protein;R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; orR3aand R3b, together with the atoms to which they are attached, form an oxo group;R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; orR6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl;R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; orR8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3- cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; o is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

73. The molecular glue degrader compound of any one of claims 7-72, having a structure of Formula (II-l) :pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:X1and X2are each independently O or S;Target Ligand comprises a moiety capable of binding to a target protein;R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; orR3aand R3b, together with the atoms to which they are attached, form an oxo group;R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; orR6aand R6b, together with the atoms to which they are attached, form an oxo group; each R7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl;R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; orR8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2;0 is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

74. The molecular glue degrader compound of any one of claims 7-73, having a structure ofFormula (Il-n):acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl; each R7and R11is independently selected from the group consisting of -OH, halogen, Ci- 6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl;R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; orR8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10and R13is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl;R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; m is 0, 1, or 2; n is 0, 1, or 2;0 is 0, 1, or 2; p is 0, 1, 2, 3, 4, or 5; and q is 0, 1, 2, 3, or 4.

75. The molecular glue degrader compound of any one of claims 7-74, having a structure of Formula (II-p):pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl; each R7and R11is independently selected from the group consisting of -OH, halogen, Ci- 6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl;R7ais selected from the group consisting of hydrogen, C1-6 alkyl, or C3-8 cycloalkyl;R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; orR8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10and R13is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl;R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; m is 0, 1, or 2; n is 0, 1, or 2;0 is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

76. The molecular glue degrader compound of any one of claims 7-75, having a structure of Formula (Il-q):pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl; each R7and R11is independently selected from the group consisting of -OH, halogen, Ci- 6 alkyl, C1-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl;R7ais selected from the group consisting of hydrogen, C1-6 alkyl, or C3-8 cycloalkyl;R8aand R8bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; orR8aand R8b, together with the atoms to which they are attached, form an oxo group; each R10and R13is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl;R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; m is 0, 1, or 2; n is 0, 1, or 2;0 is 0, 1, or 2; p is 0, 1, 2, 3, or 4; and q is 0, 1, 2, 3, or 4.

77. The molecular glue degrader compound of any one of claims 7-76, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Il-r):pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; and wherein X, Ring A, L1, R2, R3a, R3b, R4, R5, R6a, R6b, R7, m, n, p, q, and subvariables therein are as defined in Formula (II).

78. The molecular glue degrader compound of claim 7, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (III):(III), or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:X is O or S;Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7;Target Ligand comprises a moiety capable of binding to a target protein;L2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R1?, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I);R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; orR6aand R6b, together with the atoms to which they are attached, form an oxo group;R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R15is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;RBis hydrogen or Ci-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, or 4.

79. The molecular glue degrader compound of claim 78, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Ill-a):pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein: R11is selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; R12is selected from the group consisting of hydrogen, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, and Ci-6 haloalkyl; R13is selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; q is 0, 1, 2, 3, or 4; and wherein X, Ring A, L2, R3a, R3b, R4, R?, R6a, R6b, R7, R9, m, n, p, and subvariables therein are as defined in Formula (II).

80. The molecular glue degrader compound of any one of claims 78-79, wherein the molecular glue degrader compound of Formula (II) has the structure of Formula (Ill-h):pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein Ring B is a 5- to 10-membered heteroaryl or a 3- to 12-membered heterocycloalkyl, and each of the Ring A, L2, R4, R5, R6a, R6b, R7, R9, m, p, and q are as defined for Formula (II).

81. The molecular glue degrader compound of any one of claims 1-80, wherein the molecular glue degrader compound or an intermediate thereof is selected from a compound in Table 1 or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof.

82. The molecular glue degrader compound of any one of claims 1-81, wherein the molecular glue degrader compound is selected from Compound 289 and 290 or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof,83. The molecular glue degrader compound of any one of claims 1 -82, wherein the molecular glue degrader compound is capable of modulating one or more of:(i) reducing the stability of the target protein;(ii) reducing the half-life of the target protein;(iii) facilitating trafficking of the target protein to the proteasome;(iv) increasing the level of ubiquitination of the target protein; and(v) increasing the rate of degradation (e.g., proteasomal degradation) of the target protein.

84. The molecular glue degrader compound of claim 83, comprising (i).

85. The molecular glue degrader compound of any one of claims 83-84, comprising (ii).

86. The molecular glue degrader compound of any one of claims 83-85, comprising (iii).

87. The molecular glue degrader compound of any one of claims 83-86, comprising (iv).

88. The molecular glue degrader compound of any one of claims 83-87, comprising (v).

89. The molecular glue degrader compound of any one of claims 83-88, comprising each of(i)-(v).

90. The molecular glue degrader compound of any one of claims 1-89, wherein the binding of the molecular glue degrader compound to a RING E3 ubiquitin ligase does not substantially inhibit the activity of the RING E3 ubiquitin ligase.

91. The molecular glue degrader compound of any one of claims 1-90, wherein the molecular glue degrader compound binds to a site other than a catalytic site within a RING E3 ubiquitin ligase.

92. The molecular glue degrader compound of any one of claims 1-91, wherein the molecular glue degrader compound binds to an allosteric site within a RING E3 ubiquitin ligase.

93. The molecular glue degrader compound of any one of claims 1-92, wherein the molecular glue degrader compound binds to a cysteine amino acid residue within the RING E3 ubiquitin ligase.

94. The molecular glue degrader compound of any one of claims 1-93, wherein the molecular glue degrader compound preferentially binds to an allosteric amino acid residue (e.g., an allosteric amino acid residue) over a catalytic amino acid residue (e.g., a catalytic cysteine amino acid residue).

95. The molecular glue degrader compound of any one of claims 1-94, wherein molecular glue degrader compound does not substantially bind to a cysteine amino acid residue in the catalytic site of a RING E3 ubiquitin ligase (e.g., a catalytic cysteine).

96. A pharmaceutical composition comprising a molecular glue degrader compound of any one of claims 1-95, and one or more pharmaceutically acceptable carriers.

97. A method of providing a molecular glue degrader compound to a subject, wherein the molecular glue degrader compound has the structure of Formula (II):pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:X is O or S;Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7;Target LigandR1isL1is a linker selected from the group of alkyl, heteroalkyl, C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4heteroalkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I);Target Ligand comprises a moiety capable of binding to a target protein;R2is selected from the group consisting of hydrogen and Ci-6 alkyl; orR1and R2together with the atoms to which they are attached form a 5- to 10-membered heteroaryl or a 3 - to 12-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9;R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl;R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl;R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; orR6aand R6b, together with the atoms to which they are attached, form an oxo group;R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl;— I Target LigandR8isL2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; ortwo R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R15is independently selected from hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci-6 hydroxyalkyl, C1-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;RBis hydrogen or Ci-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, or 4.

98. A method of providing a molecular glue degrader compound to a subject, wherein the molecular glue degrader compound has the structure of Formula (Il-b):pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:X is O or S;Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3 - to 12-membered cycloalkyl, and a 3- to 12-membered heterocycloalkyl;L2is a linker substituted with 0-4 occurrences of R9;Target Ligand comprises a moiety capable of binding to a target protein;R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3- cycloalkyl; orR3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, - CN, Ci-6 alkyl, and Ci-6 haloalkyl;R6aand R6hare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; orR6aand R6b, together with the atoms to which they are attached, form an oxo group; eachR7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

99. A composition for use in treating a disease, disorder, or condition in a subject, wherein the composition comprises a molecular glue degrader compound of Formula (II):pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:X is O or S;Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7;— L1Target LigandR1isL1is a linker selected from the group of alkyl, heteroalkyl, C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I);Target Ligand comprises a moiety capable of binding to a target protein;R2is selected from the group consisting of hydrogen and Ci-6 alkyl; orR1and R2together with the atoms to which they are attached form a 5- to 10-membered heteroaryl or a 3 - to 12-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9;R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl;R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl;R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; orR6aand R6b, together with the atoms to which they are attached, form an oxo group;R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl;— LzTarget LigandR8isL2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl,heteroalkylene, and alkylene are optionally substituted with one or more R1?, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl,Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R15is independently selected from hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, Ci-6 hydroxyalkyl, C1-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;RBis hydrogen or Ci-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, or 4.

100. A composition for use in treating a disease, disorder, or condition in a subject, wherein the composition comprises a molecular glue degrader compound of Formula (ILb):pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:X is O or S;Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3 - to 12-membered cycloalkyl, and a 3 - to 12-membered heterocycloalkyl;L2is a linker substituted with 0-4 occurrences of R9;Target Ligand comprises a moiety capable of binding to a target protein;R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; orR3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, - CN, Ci-6 alkyl, and Ci-6 haloalkyl;R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; orR6aand R6b, together with the atoms to which they are attached, form an oxo group; eachR7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

101. The composition for use of claim 100, wherein the disease, disorder, or condition is cancer.

102. The composition for use of any one of claims 100-101, wherein the subject is a mammal (e g., a human).

103. A method of ubiquitinating a target protein comprising contacting a cell or sample with a molecular glue compound of Formula (II):pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:X is O or S;Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7;— L1Target LigandR1isL1is a linker selected from the group of alkyl, heteroalkyl, C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I);Target Ligand comprises a moiety capable of binding to a target protein;R2is selected from the group consisting of hydrogen and Ci-6 alkyl; orR1and R2together with the atoms to which they are attached form a 5- to 10-membered heteroaryl or a 3- to 12-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9;R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl;R4and R?are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and Ci-6 haloalkyl;R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; orR6aand R6h, together with the atoms to which they are attached, form an oxo group;R7are each independently selected from the group consisting of -OH, halogen, C1-6 alkyl, Ci-6 alkoxyl, C1-6 haloalkyl, and C1-6 haloalkoxyl;— I Target LigandR8isL2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-8 cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R15is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;RBis hydrogen or Ci-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, or 4.

104. A method of ubiquitinating a target protein comprising contacting a cell or sample with a molecular glue compound of Formula (ILb):pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:X is O or S;Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3 - to 12-membered cycloalkyl, and a 3 - to 12-membered heterocycloalkyl;L2is a linker substituted with 0-4 occurrences of R9;Target Ligand comprises a moiety capable of binding to a target protein;R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; orR3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R3are each independently selected from the group consisting of hydrogen, -OH, halogen, - CN, C1-6 alkyl, and Ci-6 haloalkyl;R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; orR6aand R6b, together with the atoms to which they are attached, form an oxo group; eachR7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3- cycloalkyl; ortwo R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

105. A method of degrading a target protein comprising contacting a cell or sample with a molecular glue compound of Formula (II):pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:X is O or S;Ring A is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, optionally substituted with one or more R7;— L1Target LigandR1isL1is a linker selected from the group of alkyl, heteroalkyl, C2-5 cycloalkyl, -C2-5 cycloalkyl-NRB-*, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 heteroalkylene*-, -C2-5 cycloalkyl-NRB-C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, cycloalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of attachment of L1to the Target Ligand in Formula (I);Target Ligand comprises a moiety capable of binding to a target protein;R2is selected from the group consisting of hydrogen and Ci-6 alkyl; orR1and R2together with the atoms to which they are attached form a 5- to 10-membered heteroaryl or a 3 - to 12-membered heterocycloalkyl, wherein the heteroaryl or heterocycloalkyl are each substituted with one R8, and the heteroaryl or heterocycloalkyl are optionally substituted with 1-4 occurrences of R9;R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, -CN, Ci-6 alkyl, and C1-6 haloalkyl;R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; orR6aand R6b, together with the atoms to which they are attached, form an oxo group;R7are each independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl;— L Target LigandR8isL2is absent or a linker selected from the group of alkyl, heteroalkyl, -C(0)-Co-4 alkylene- *, -C(0)-Co-4 heteroalkylene-*, -C(0)-Co-4 alkylene-O-*, wherein each alkyl, heteroalkyl, heteroalkylene, and alkylene are optionally substituted with one or more R15, wherein * denotes the point of the attachment of L2to the Target Ligand in Formula (I); each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; or two R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3- cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R1?is independently selected from hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl;RBis hydrogen or Ci-6 alkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, or 4.

106. A method of degrading a target protein comprising contacting a cell or sample with a molecular glue compound of Formula (Il-b):pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:X is O or S;Ring A is selected from the group consisting of a 6- to 10-membered aryl, a 5- to 10- membered heteroaryl, a 3 - to 12-membered cycloalkyl, and a 3 - to 12-membered heterocycloalkyl;L2is a linker substituted with 0-4 occurrences of R9;Target Ligand comprises a moiety capable of binding to a target protein;R2aand R2bare each independently hydrogen, Ci-6 alkyl, and C3-8 cycloalkyl;R3aand R3bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; orR3aand R3b, together with the atoms to which they are attached, form an oxo group; R4and R5are each independently selected from the group consisting of hydrogen, -OH, halogen, - CN, C1-6 alkyl, and Ci-6 haloalkyl;R6aand R6bare each independently selected from the group consisting of hydrogen, -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 hydroxyalkyl, Ci-6 haloalkyl, Ci-6 haloalkoxyl, and C3-8 cycloalkyl; orR6aand R6b, together with the atoms to which they are attached, form an oxo group; eachR7is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; each R9is independently selected from the group consisting of -OH, halogen, Ci-6 alkyl, Ci-6 alkoxyl, Ci-6 haloalkyl, and Ci-6 haloalkoxyl; ortwo R9on the same carbon atom together with the same carbon atom to which they are attached form a C3-8 cycloalkyl or an oxo; or two R9on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3- cycloalkyl; or two R9on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring; each R10is independently selected from the group consisting of hydrogen, -OH, halogen, C1-6 alkyl, C1-6 alkoxyl, C1-6 hydroxyalkyl, Ci-6 haloalkyl, C1-6 haloalkoxyl, and C3-8 cycloalkyl; m is 0, 1, or 2; n is 0, 1, or 2; and p is 0, 1, 2, 3, 4, or 5.

107. The method of claim 106, wherein the target protein is selected from a tyrosine kinase, a serine / threonine kinase, a bromodomain-containing protein, an epigenetic protein, and a misfolded protein.

108. The method of any one of claims 106-107, wherein the target protein is selected from AR, BCL-2 / BCL, BCL-XL, BCR-ABL, BRD2, BRD3, BRD4, BRD9, BRDT, BTK, BUB1, BUB1B, c-ABL, CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11B, CDK12, CDK13, CDK14, CDK15, CDK16, CDK17, CDK18, CDK19, CDK20, CHEK1, CKS1B, CKS2, CSNK1A1, CSNK1E, CTNNB1, DSTYK, EEF2K, estrogen receptor (ER), ETNK1, FASTKD5, HRAS, ITPKB, KRAS, LRKK2, MAPKAPK2 (MK2), MARK2, MAP3K2, MELK, MYC, MYCN, NEK6, NRAS, PANK2, PANK3, PDE5, PHKA1, PHKA2, PKN2, PLK1, PTK6, RIOK2, SKP2, SMARCA2, SMARCA4, STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6, TK1, TTK, and UCK2.

109. The method of any one of claims 106-108, wherein the target protein is selected from AR-V7, Bcl-2 / Bcl, BCR-ABL, BRD4, BTK, BUB1, BUB1B, c-ABL, CDK4, CDK11B, CHEK1, CKS1B, CKS2, CSNK1A1, CSNK1E, DSTYK, EEF2K, ETNK1, FASTKD5, ITPKB, KRAS G12D, LRKK2, MARK2, MAP3K2, MELK, NEK6, PANK2, PANK3, PDE5, PHKA1, PHKA2, PKN2, PLK1, RIOK2, SKP2, SMARCA2, TK1, TTK, and UCK2.

110. The method of any one of claims 106-109, wherein the target protein is selected from CDK4, CDK6, BRD4, PDE5, BCR-ABL, c-ABL, AR, AR-V7, BTK, LRKK2, or SMARCA2.

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