Abstract: Disclosed are compounds with immunomodulatory 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 dysfunctional protein activity.

Abstract: The present invention relates to compounds, compositions and methods for treating diseases or conditions mediated by proteins of the SWI/SNF chromatin-remodeling complex, including PB1.

Abstract: Methods of modulating transcription of a target gene in a cell (which may be in vitro or in vivo) are provided. Aspects of the methods employ a transcription factor-chemical inducer of proximity (TF-CIP) system to modulate, e.g., enhance or reduce, transcription of a target gene in a cell. Embodiments of the methods include providing in a cell a chemical inducer of proximity (CIP) which links a first endogenous anchor transcription factor that binds to a promoter of the target gene and a second endogenous transcription modulating factor (e.g., a transcription factor or transcription repressor), wherein CIP mediated linkage of the anchor transcription factor and transcription modulating factor modulates transcription of the target gene in the cell. Also provided are compositions that find use in practicing methods of the invention.

Abstract: Disclosed are compounds with immunomodulatory 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 dysfunctional protein activity.

Abstract: Disclosed are compounds that possess inhibitory activity against FAK. Also disclosed are pharmaceutical compositions containing the compounds and methods of using the compounds to treat cancer mediated by aberrant FAK activity.

Abstract: Disclosed are bifunctional compounds comprising a GDC-0068 analog that binds AKT isoforms AKT1, 2 and 3, pharmaceutical compositions, and methods for treating diseases or conditions mediated by dysfunctional AKT activity.

Abstract: Disclosed are compounds and pharmaceutically acceptable salts and stereoisomers thereof that may cause degradation of various proteins e.g., IKZF2 (Helios). Also disclosed are pharmaceutical compositions containing same, and methods of making and using the compounds to treat diseases and disorders characterized or mediated by aberrant protein activity.

Abstract: The present invention relates to bifunctional compounds, compositions, and methods for treating diseases or conditions mediated by Kelch-like ECH-associated protein 1 (KEAP1). In some aspects, the present invention is directed to methods of treating diseases or disorders involving dysfunctional (e.g., dysregulated) KEAP1 activity, that entails administration of a therapeutically effective amount of a bifunctional compound of formula I or a pharmaceutically acceptable salt or stereoisomer thereof, to a subject in need thereof.

Abstract: The present invention relates to bispecific compounds, compositions, and methods for treating diseases or conditions characterized or mediated by aberrant fibroblast growth factor receptor 2 (FGFR2) activity.

Abstract: The present invention relates to bifunctional compounds, compositions, and methods for treating diseases or conditions mediated by dysfunctional cyclin-dependent kinase 2 (CDK2) and CDK5 activity.

Abstract: A method for treating inflammation and/or autoimmune diseases comprises administering to a subject in need thereof, a composition comprising a CDK8 inhibitor. In another aspect, a method for increasing IL-10 production comprises administering to a subject in need thereof a CDK8 inhibitor. In another aspect, a method for enhancing Treg cell differentiation, comprising administering a composition comprising a CDK8 inhibitor. In certain example embodiments, the subject suffers from an inflammatory bowel disease. In certain other example embodiments, the subject requires immunosuppression to prevent rejection following a transplantation procedure.

Abstract: The present invention relates to screening methods for identification of agents (e.g., small molecules) that modulate cytotoxic T lymphocyte antigen-specific target (e.g., tumor) cell killing, as well as to uses of compounds identified thereby as immunomodulatory, including use of EGFR inhibitors as immunomodulatory agents.

Abstract: The present application provides bifunctional compounds of Formula (I): which act as protein degradation inducing moieties for EGFR and/or a mutant thereof. The present application also describes methods for the targeted degradation of EGFR and/or a mutant thereof through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to EGFR and/or a mutant thereof which can be utilized in the treatment of disorders modulated by EGFR or a mutant thereof.

Abstract: Disclosed are degraders, pharmaceutical compositions containing them, and methods of making and using the degraders to treat diseases and disorders characterized by aberrant protein activity that can be targeted by cereblon.

Abstract: Disclosed are compounds with immunomodulatory 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 dysfunctional protein activity.

Abstract: Disclosed are immunomodulatory compounds, pharmaceutical compositions containing them, and methods of making and using the compounds to treat diseases and disorders characterized by aberrant protein activity that can be targeted by cereblon.

Abstract: Disclosed are degraders, pharmaceutical compositions containing them, and methods of making and using the degraders to treat diseases and disorders characterized by dysregulated or dysfunctional protein activity that can be targeted by cereblon.

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 present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, 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., cyclin-dependent kinase 7 (CDK7)), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.

Abstract: The present invention relates to compounds, compositions and methods for treating diseases or conditions mediated by proteins of the SWI/SNF chromatin-remodeling complex, including PB1.