Dana-farber-cancer Institute Inc.

Irm LLC

The Scripps Research Institute

The General Hospital Corporation

The Broad Institute, Inc.

Novartis Ag

Harvard College

Cornell University

Whitehead Institute for Biomedical Research

Yale University

University Court of the University of Dundee

Other

Children's Medical Center Corporation

Beth Israel Deaconess Medical Center, Inc.

University of Miami

Nathanael Schiander Gray

Tinghu Zhang

Hwan Geun Choi

Nicholas Paul Kwiatkowski

Pasi Antero Janne

Yanke Liang

Xianming Deng

John M Hatcher

Sara Jean Buhrlage

Jaebong Jang

Yi Liu

Jianming Zhang

Li Tan

Taebo Sim

Eric S Fischer

Shifeng Pan

Qiang Ding

Yuan Mi

Steven P Treon

Radoslaw Nowak

Jae Won Chang

Michael Eck

Pingda Ren

Wenqi Gao

David A Scott

Guangyan Du

Ramnik Xavier

Yi Fan

Alykhan Shamji

Barun Okram

Guobao Zhang

Wenjun Zhou

Shuli You

Xia Wang

Jinhua Wang

Sheng Ding

Tao Jiang

Yongqin Wan

Tetsuo Uno

Bing Li

Ruo W Steensma

David E Fisher

James Elliott Bradner

M Arshad Siddiqui

Stephane Ciblat

Joel D Moore

Dennis Buckley

Yongping Xie

Kevin Sprott

Jason J Marineau

Darby Schmidt

Kwok-kin Wong

Michael Bradley

Anzhelika Kabro

Jiqing Jiang

Jean Zhao

Melissa Leblanc

Ari Matthew Melnick

Peter G Schultz

Pascal Furet

Pamela Ann Albaugh

Yun He

Kenneth Carl Anderson

Jun Qi

Craig M Crews

Henry M Kronenberg

Qiong Zhang

David Sabatini

Xing Wang

Alan D D'Andrea

Advait Suresh Nagle

Joseph Schoepfer

Michael Robert McKeown

Philip Cohen

Wenshuo Lu

Stuart L Schreiber

Paul William Manley

Guido Bold

Donald Karanewsky

Jieun Choi

Marc Lang

Rudolf Jaenisch

Giorgio Caravatti

Vito Guagnano

Matthew Meyerson

Werner Breitenstein

Chandrasekhar V Miduturu

Keiichi Masuya

Xiaohui He

Georg Winter

Peter Ettmayer

Thomas H Marsilje, Iii

Teru Hideshima

Kunyong Yang

Ichiro Umemura

Ha-Soon Choi

Klaus Hinterding

Carlos Garcia-Echeverria

Dai Cheng

Carsten Spanka

The present application provides bifunctional compounds of Formula (X): or an enantiomer, diastereomer, or stereoisomer thereof, or pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, which act as protein degradation inducing moieties for Bruton's tyrosine kinase (BTK). The present application also relates to methods for the targeted degradation of BTK through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to BTK which can be utilized in the treatment of disorders modulated by BTK.

Degradation of bruton's tyrosine kinase (BTK) by conjugation of BTK inhibitors with E3 ligase ligand and methods of use

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

Pyrimidines as EGFR-inhibitors and methods of treating disorders

The present application provides compounds of Formula (Ia), or an enantiomer, diastereomer, stereoisomer, or pharmaceutically acceptable salt thereof, which act as protein degradation inducing moieties for one or more of cyclin-dependent kinase 8 (CDK8) and cyclin-dependent kinase 19 (CDK19). The present application also relates to methods for the targeted degradation of CDK8 and/or CDK19 through the use of the compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK8 and/or CDK19 which can be utilized in the treatment of disorders modulated by CDK8 and/or CDK19.

Cyclin-dependent kinase degraders and methods of use

Disclosed are bifunctional compounds (degraders) that target Wee1 tyrosine kinase for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat disease.

Degraders of WEE1 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 compounds that possess inhibitory activity against LRRK2. Also disclosed are pharmaceutical compositions containing the compounds and methods of using the compounds to treat diseases and disorders including neurodegenerative diseases and disorders such as Parkinson's disease, and brain cancer (e.g., gliomas and glioblastomas).

Azaindole inhibitors of wild-type and mutant forms of LRRK2

Disclosed are bispecific compounds (degraders) that target ALK for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat diseases and disorders characterized or mediated by aberrant ALK activity.

Degraders that target ALK and therapeutic 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 disclosure provides imidazolyl compounds of Formula (I) and methods of preparing the compounds. The provided compounds are able to bind protein kinases and may be useful in modulating (e.g., inhibiting) the activity of a protein kinase in a subject or cell and/or in treating or preventing a disease (e.g., proliferative disease, genetic disease, hematological disease, neurological disease, painful condition, psychiatric disorder, or metabolic disorder) in a subject in need thereof. Also provided are pharmaceutical compositions, kits, methods, and uses that include or involve a compound described herein.

Imidazolyl kinase inhibitors and uses thereof

Provided herein are compounds of Formula (I′) or (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 diseases (e.g., proliferative diseases (e.g., cancers (e.g., carcinoma); lung cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, ovarian cancer, colon cancer, colorectal cancer)), metabolic disorders (e.g., diabetes), autoimmune diseases, and neurological diseases (e.g., Alzheimer's disease, gliosis, spinal cord injury)) in a subject, as well as for male contraception (e.g., reducing or inhibiting spermatogenesis, or reducing the rate of male fertility in a healthy fertile male subject). Provided are methods of inhibiting a CDK (e.g., CDK14, CDK15, CDK16, CDK17, CDK18) in a subject.

Taire family kinase inhibitors and uses thereof

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)

The application relates to compounds, or pharmaceutically acceptable salts, hydrates, solvates, or stereoisomers thereof, which modulate the activity of EGFR, a pharmaceutical composition comprising said compounds, and methods of treating or preventing a disease in which EGFR plays a role.

Inhibitors of EGFR and methods of use thereof

Disclosed are compounds of formula (I) or (II): that inhibit ALK, TRKA, TRKB, TRKC and ROS1. Also disclosed are pharmaceutical compositions containing the compounds and methods of using the compounds to treat disease.

Macrocyclic inhibitors of ALK, TRKA, TRKB, and ROS1

Disclosed are macrocyclic compounds that possess inhibitory activity against DYRK, TRK, TLK, and/or RET. Also disclosed are pharmaceutical compositions containing the compounds, methods of making the compounds, and methods of using the compounds to treat diseases and disorders that are characterized or mediated by aberrant DYRK, TRK, TLK, and/or RET activity such as cancer, neurodegenerative disorders and genetic disorders.

Macrocyclic inhibitors of DYRK1A

Growing community of inventors

Boston, MA, United States of America

Nathanael Schiander Gray