Abstract: The present disclosure provides methods of increasing skin pigmentation in a subject in need thereof using salt-inducible kinase (SIK) inhibitors, such as macrocyclic compounds of Formula (I), bicyclic urea compounds of Formula (II), (III), and (IV), and compounds of Formula (V), (VI), (VI-A), or (VII). Also provided are pharmaceutical compositions, methods, and uses that include or involve a compound described herein.

Abstract: The present invention relates to bifunctional compounds, compositions, and methods for treating diseases or conditions by modulating (e.g., reducing) the level or activity of at least one of PIP4K2A, PIP4K2B, and PIP4K2C.

Abstract: Disclosed are compounds which inhibit Pin1 activity, methods of making the compounds, pharmaceutical compositions containing the compounds, and methods of using the compounds to treat diseases or disorders characterized or mediated by dysregulated Pin1 activity.

Abstract: The disclosure relates to compounds that act as covalent inhibitors of epidermal growth factor receptor (EGFR); pharmaceutical compositions comprising the compounds; and methods of treating or preventing kinase-mediated disorders, including cancer and other proliferation diseases.

Abstract: The present disclosure provides novel heteroaryl compounds of formula (IX). Such compounds are useful for the treatment of cancers.

Abstract: Provided herein are compounds of Formula (I?), Formula (I?), Formula (I), Formula (II?), and Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. Also provided are methods, uses, and kits involving the disclosed compounds and pharmaceutical compositions thereof for treating and/or preventing diseases (e.g., proliferative diseases (e.g., cancers), inflammatory diseases (e.g., fibrosis), autoimmune diseases (e.g., sclerosis)) in a subject. Provided are methods of inhibiting the activity of a transcription factor (e.g., TEAD, such as TEAD1, TEAD2, TEAD3, TEAD4) and/or inhibiting the transcription of a gene (e.g., a gene controlled or regulated by a transcription factor (e.g., TEAD)) in a subject.

Abstract: The application relates to a compound having Formula X: which modulates the activity of HER2 and/or a mutant thereof, and/or EGFR and/or a mutant thereof, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which HER2 and/or a mutant thereof, and/or EGFR and/or a mutant thereof, plays a role.

Abstract: The present disclosure provides compounds of Formula (I) and Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK) (e.g., Janus kinase 2 (JAK2)) and/or cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 11 (CDK11)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).

Abstract: Provided herein are bifunctional compounds that bind tau protein and/or promote targeted ubiquitination for the degradation of tau protein. In particular, provided are compounds that can bind tau protein, a protein whose aggregation is implicated in a variety of neurodegenerative disease (e.g., tauopathies), and can promote its degradation by recruiting an E3 ubiquitin ligase (e.g., Cereblon), which can ubiquitinate tau protein, marking it for proteasomal degradation. Also provided are radiolabeled forms of the bifunctional compounds, pharmaceutical compositions comprising the bifunctional compounds, methods of detecting and/or diagnosing neurological disorders, methods of detecting and/or diagnosing pathological aggregation of tau protein (e.g., in the central nervous system), methods of treating and/or preventing neurological disorders, and methods of promoting the degradation of tau protein by E3 ubiquitin ligase activity in a subject by administering a compound or composition described herein.

Abstract: The present invention provides novel compounds of Formulae (I?) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, ovarian cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g.

Abstract: The present disclosure provides novel heteroaryl compounds of formula (VII). Such compounds are useful for the treatment of cancers.

Abstract: DCAF15 is a substrate recognition (adaptor) protein of E3 ubiquitin ligase. Disclosed herein are compounds that recruit ubiquitin ligase CRL4DCAF15, to a target RNA recognition motif (RRM), causing its degradation. Also disclosed herein are compositions and methods of use in treating associated disorders and diseases.

Abstract: Provided herein are compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the disclosed compounds or compositions for treating and/or preventing diseases (e.g., inflammatory diseases, neurological diseases (e.g., Alzheimer's disease), infectious diseases (e.g., viral infections (e.g., infections caused by viral human hepatitis (e.g., hepatitis B), a flaviviridae family virus (e.g., a flavivims (e.g., Zika virus)))), and proliferative diseases (e.g., cancer (e.g., lung cancer, prostate cancer, skin cancer, thyroid cancer, pancreatic cancer, colorectal cancer, liver cancer, leukemia, or lymphoma)) in a subject. Provided are methods of inhibiting a protein kinase (e.g., MAP2K (e.g., MKK7)) in a subject. Also provided are methods of inhibiting MKK7 in a subject in need thereof.

Abstract: The present disclosure provides methods of increasing skin pigmentation in a subject in need thereof using salt-inducible kinase (SIK) inhibitors, such as macrocyclic compounds of Formula (I), bicyclic urea compounds of Formula (II), (III), and (IV), and compounds of Formula (V), (VI), (VI-A), or (VII). Also provided are pharmaceutical compositions, methods, and uses that include or involve a compound described herein.

Abstract: The application relates to a compound of Formula (I): which modulates the activity of ALK or SRPK, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which ALK or SRPK plays a role.

Abstract: The present disclosure relates to compounds that are capable of inhibiting creatine kinase. The present disclosure also relates to methods of treating cancer, such as hematological malignancies.

Abstract: The present disclosure provides compounds of Formula (I?) (e.g., compounds of Formula (I)), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK), e.g., Janus kinase 2 (JAK2)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).

Abstract: The present invention relates to novel compounds which are able to modulate b-raf kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.

Abstract: The present application provides bifunctional compounds of Formula (Ia) or (Ib): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for cyclin-dependent kinase 8 (CDK8). The present application also relates to methods for the targeted degradation of CDK8 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK8 which can be utilized in the treatment of disorders modulated by CDK8.

Abstract: The present invention provides compounds of any one of Formulae (A), (I-11), (II), and (V) (e.g., compounds of Formula (A-1)-(A-18)), and methods for treating Waldenström's macroglobulinemia (WM) and other B cell neoplasm in a subject using the compounds. The methods comprise administering to a subject in need thereof an effective amount of the compounds. Also provided are methods to treat B cell neoplasms using the compounds in combination with inhibitors of Bruton's tyrosine kinase (BTK), interleukin-1 receptor-associated kinase 1 (IRAK1), interleukin-1 receptor-associated kinase 4 (IRAK4), bone marrow on X chromosome kinase (BMX), phosphoinositide 3-kinase (PI3K), transforming growth factor b-activated kinase-1 (TAK1), and/or a Src family kinase.