Arvinas Operations, Inc.

Hoffmann-la Roche Inc.

Accutar Biotechnology Inc.

Yale University

Madrigal Pharmaceuticals, Inc.

Merck Sharp + Dohme Corp.

Tiger Biotherapeutics Inc.

Msd R&d (china) Co., Ltd.

Via Pharmaceuticals, Inc.

F. Hoffmann-la Roche Ag

Arvinas, Inc.

Msd R&d Co., Ltd.

Yimin Qian

Andrew Philip Crew

Jing Wang

Hanqing Dong

Jie Fan

Wei He

David Robert Bolin

Michael Berlin

Craig M Crews

Ke Liu

Lawrence B Snyder

Adrian Wai-Hing Cheung

Kshitij Chhabilbhai Thakkar

Jefferson Wright Tilley

Sung-Sau So

Nancy-Ellen Haynes

Keith R Hornberger

Nathan Robert Scott

Matthew Michael Hamilton

Shawn David Erickson

Fariborz Firooznia

Weiya Yun

Xin Chen

Lee Apostle McDermott

Kurt Zimmermann

Jie Su

Steven Gregory Mischke

Robert Francis Kester

Meizhong Jin

Jenny Tan

Stuart Hayden

Deping Wang

Denis John Kertesz

Ramakanth Sarabu

Shaoqing Chen

Richard Berger

Christine E Brotherton-Pleiss

Kyungjin Kim

Sherrie Lynn Pietranico-Cole

Kevin Richard Guertin

Christopher Joseph Sinz

Shimin Xu

Steven Joseph Berthel

Zhi Chen

Lin Yi

Caterina Ferraro

Nicholas Marcopulos

Michael P Dwyer

Dong-Ming Shen

Shawn J Stachel

Achyutharao Sidduri

Daniel Vincent Paone

Peter Michael Wovkulich

Jianmin Fu

Eric Mertz

Hongju Li

Lida Qi

Yili Chen

Ashley Forster

Wei Liu

Joseph P Lyssikatos

Joseph A Kozlowski

Yan Lou

Xiangzhu Wang

Anthony A Estrada

Huifen Chen

David James Witter

Xianhai Huang

Melissa S Egbertson

Matthew C Lucas

Francisco Javier Lopez-Tapia

David L Sloman

Phieng Siliphaivanh

Timothy D Owens

Nader Fotouhi

Ryan Craig Schoenfeld

Allen John Lovey

Roland Joseph Billedeau

XiaoXia Qian

Umar Faruk Mansoor

Rama K Kondru

Wendy Lea Corbett

Stephan Bachmann

Robert Zhiyong Luo

William D Shipe

Saul Jaime-Figueroa

Stephen Deems Gabriel

Bart Harper

Ji Liu

Vanessa L Rada

Meng Yang

Ming Wang

Jonathan E Wilson

Francis A Mennona

Jutta Wanner

John A Brinkman

Zack Zhiqiang Guo

Zhigang Guo

Joseph Anthony Bilotta

The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present disclosure. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

Cereblon ligands and bifunctional compounds comprising the same

The present disclosure relates to novel CDK inhibitors, pharmaceutical compositions containing such compounds, and their use in prevention and treatment of diseases and conditions associated with CDK.

Aminopyrimidine derivatives as cyclin-dependent kinase inhibitors

The present disclosure relates to bifunctional compounds, which find utility to degrade (and inhibit) Androgen Receptor. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds Androgen Receptor such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of Androgen Receptor.

Compounds and methods for the targeted degradation of androgen receptor

The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a cereblon, Von Hippel-Lindau ligase-binding moiety, Inhibitors of Apotosis Proteins, or mouse double-minute homolog 2 ligand, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Modulators of estrogen receptor proteolysis and associated methods of use

The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.

Compounds and methods for the enhanced degradation of targeted proteins

The present application relates to treating and/or preventing breast cancer, including locally advanced or metastatic, ER+, HER2− breast cancer, in a subject in need of treatment, comprising administering a compound of Formula (I), or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate, polymorph, isotopic derivative, or prodrug thereof, wherein R, R, R, R, m, and n are defined herein.

Methods of treating breast cancer with tetrahydronaphthalene derivatives as estrogen receptor degraders

The present disclosure relates to novel pan-KRAS glutarimide-containing compounds with KRAS degradation activities, pharmaceutical compositions containing such compounds, and their use in prevention and treatment diseases and conditions.

Glutarimide-containing pan-KRAS-mutant degrader compounds and uses thereof

Compounds and methods for the targeted degradation of bromodomain- containing proteins

The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, Inhibitors of Apoptosis Proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Tetrahydronaphthalene and tetrahydroisoquinoline derivatives as estrogen receptor degraders

The present disclosure relates to novel glutarimide-containing compounds with KRAS mutant form degradation activities, pharmaceutical compositions containing such compounds, and their use in prevention and treatment of diseases and conditions.

Glutarimide-containing KRAS-mutant degrader compounds and uses thereof

The present disclosure relates to bifunctional compounds, which find utility as modulators of enhancer of zeste homolog 2 (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Compounds and methods for the targeted degradation of enhancer of zeste homolog 2 polypeptide

Provided herein are pharmaceutical combinations, compositions, and methods of using a compound with estrogen receptor (ER) degradation activity, such as a compound of formula (I) or a tautomer, stereoisomer or a mixture of stereoisomers, or a pharmaceutically acceptable salt, or hydrate thereof, wherein R, Y, R, R, R, p, X, X, and Z are defined herein and a cyclin-dependent kinase (CDK) inhibitor. 

Combinations of estrogen receptor degraders and cyclin-dependent kinase inhibitors for treating cancer

The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, inhibitors of apoptosis proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Growing community of inventors

Plainsboro, NJ, United States of America

Yimin Qian