Dana-farber-cancer Institute Inc.

Isocure Biosciences Inc.

University of Texas System

Syros Pharmaceuticals, Inc.

The General Hospital Corporation D/b/a Massachusetts General Hospital

Tinghu Zhang

Nathanael Schiander Gray

Nicholas Paul Kwiatkowski

Eric S Fischer

Katherine Donovan

Yanke Liang

Zhixiang He

Jing Ting Christine Yuan

Calla M Olson

John M Hatcher

Hwan Geun Choi

M Arshad Siddiqui

Stephane Ciblat

Stephen J Haggarty

Radoslaw Nowak

Guangyan Du

Alyssa Verano

Pasi Antero Janne

Joel D Moore

Kevin Sprott

Jason J Marineau

Darby Schmidt

Nathanael S Gray

Michael Bradley

Anzhelika Kabro

Jean Zhao

Melissa Leblanc

Stephanie Roy

Dana K Winter

Tom Miller

Baishan Jiang

Hai-Tsang Huang

Jianwei Che

Hwangeun Choi

Yubao Wang

Eric Wang

Yao Liu

Mingfeng Hao

Hu Liu

Nathaniel Henning

Jie Jiang

Sara Jean Buhrlage

Patrick Deroy

Serge Leger

Kenneth Dale Westover

Fleur M Ferguson

Brian Groendyke

Hojong Yoon

Tyler Faust

Jing Ni

Quan Cai

Zhengnian Li

David Weinstock

Loretta Sze-Mun Li

Suman Rao

Deepak Gurbani

Mingxing Teng

Nozhat Safaee

Eric Fischer

Maria Catarina Telo Baptista Lima Da Silva

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.

CDK2/5 degraders and uses thereof

The present disclosure provides 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).

Benzothiazole derivatives and 7-aza-benzothiazole derivatives as janus kinase 2 inhibitors and uses thereof

Disclosed are bifunctional compounds, pharmaceutical compositions containing them, and methods of making and using them to treat diseases and disorders characterized by aberrant protein activity wherein the protein is targeted for degradation by KEAP1 and the Cul3-based E3-ubiquitin ligase complex.

Degraders that target proteins via KEAP1

Disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof. Also disclosed herein are methods of using the compounds of Formula (I) in the treatment of certain diseases (e.g., cancer).

Small molecule inhibitors of SRC tyrosine kinase

The present disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The compounds of the present disclosure are inhibitors of kinases (e.g., a cyclin-dependent kinase (CDK) (e.g., CDK7)). The compounds may be selective for inhibiting the activity of a kinase (e.g., CDK7) over certain other kinases (e.g., CDK2, CDK9, CDK12). Also provided are pharmaceutical compositions, kits, methods of use, and uses that involve the compounds. The compounds may be useful in inhibiting the activity of a kinase, down-regulating the transcription of MYC or MCL-1, inhibiting the growth of a cell, inducing apoptosis of a cell, treating a disease, and/or preventing a disease (e.g., proliferative disease, cystic fibrosis).

Inhibitors of cyclin-dependent kinase 7 and uses thereof

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.

Immunomodulatory compounds

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.

Small molecule degraders of Helios and methods of use

The present invention provides novel 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 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, 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., cyclin-dependent kinase 7 (CDK7)), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.

Inhibitors of cyclin-dependent kinase 7 (CDK7)

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.

Ligands to cereblon (CRBN)

The present invention provides novel compounds of Formula (I), (II), or (III), 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., CDK7, CDK12, or CDK13), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.

Inhibitors of cyclin-dependent kinases

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.

Bispecific degraders

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.

CRBN modulators

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., CDK12), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.

Inhibitors of cyclin-dependent kinase 12 (CDK12) and uses thereof

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.

Substituted 6,11-dihydro-5H-benzo[b]carbazoles as inhibitors of ALK and SRPK

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.

Degradation of cyclin-dependent kinase 8 (CDK8) by conjugation of CDK8 inhibitors with E3 ligase ligand and methods of use

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Brookline, MA, United States of America

Tinghu Zhang