公开(公告)号：US20200038378A1

公开(公告)日：2020-02-06

申请号：US16590329

申请日：2019-10-01

Applicant: Arvinas Operations, Inc. ,  Genentech, Inc.

Inventor： ANDREW P. CREW ,  Jing Wang ,  Michael Berlin ,  Peter Dragovich ,  Huifen Chen ,  Leanna Staben

IPC: A61K31/427 ,  A61K31/4035 ,  A61K31/4439 ,  A61K31/437 ,  A61K31/4245 ,  A61K31/541 ,  A61K31/496 ,  A61K47/54

Abstract: The present disclosure relates to bifunctional compounds, which find utility as modulators of SMARCA2 or BRM (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand that binds to the Von Hippel-Lindau 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.

公开(公告)号：US20190315732A1

公开(公告)日：2019-10-17

申请号：US16375643

申请日：2019-04-04

Applicant: Arvinas Operations, Inc. ,  Yale University

Inventor： Andrew P. Crew ,  Keith R. Hornberger ,  Jing Wang ,  Hanging Dong ,  Michael Berlin ,  Craig M. Crews

IPC: C07D417/14 ,  A61P35/00 ,  C07D401/14 ,  C07D413/14 ,  C07D471/04

Abstract: The present disclosure relates to bifunctional compounds, which find utility as modulators of Kirsten rat sarcoma protein (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, accumulation, and/or overactivation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

公开(公告)号：US20250114356A1

公开(公告)日：2025-04-10

申请号：US18794292

申请日：2024-08-05

Applicant: Arvinas Operations, Inc.

Inventor： Erika Marina Vieira Araujo ,  Steven M. Sparks ,  Michael Berlin ,  Jing Wang ,  Wei Zhang

IPC: A61K31/506 ,  A61K31/496 ,  A61K31/5377 ,  A61K45/06 ,  A61P25/16 ,  C07D401/14 ,  C07D413/14 ,  C07D487/10

Abstract: Bifunctional compounds, which find utility as modulators of leucine-rich repeat kinase 2 (LRRK2), are described herein. In particular, the hetero-bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds LRRK2, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The hetero-bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

公开(公告)号：US12171831B2

公开(公告)日：2024-12-24

申请号：US18052096

申请日：2022-11-02

Applicant: Arvinas Operations, Inc. ,  YALE UNIVERSITY

Inventor： Yimin Qian ,  Hanqing Dong ,  Jing Wang ,  Michael Berlin ,  Andrew P. Crew ,  Craig M. Crews

IPC: C07D417/14 ,  A61K45/06 ,  A61K47/55 ,  A61P35/00 ,  C07D495/14 ,  C07D519/00

Abstract: 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.

公开(公告)号：US20240158405A1

公开(公告)日：2024-05-16

申请号：US18511018

申请日：2023-11-16

Applicant: Arvinas Operations, Inc.

Inventor： Erika Marina Vieira Araujo ,  Michael Berlin ,  Steven M. Sparks ,  Jing Wang ,  Wei Zhang

IPC: C07D487/04 ,  A61K45/06 ,  C07D519/00

CPC classification number: C07D487/04 ,  A61K45/06 ,  C07D519/00

Abstract: Bifunctional compounds, which find utility as modulators of non-receptor Leucine-rich repeat kinase 2 (LRRK2), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds LRRK2, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

公开(公告)号：US11857519B2

公开(公告)日：2024-01-02

申请号：US17354941

申请日：2021-06-22

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  Lawrence B. Snyder ,  Jing Wang ,  Hanqing Dong ,  Yimin Qian ,  Michael Berlin

IPC: A61K31/166 ,  A61K31/405 ,  A61K47/54 ,  A61P35/00 ,  A61K38/45 ,  C12N9/10 ,  A61K31/351 ,  C07D471/04 ,  C07D401/14 ,  C07D405/14 ,  C07D405/12 ,  C07D417/14 ,  C07D409/14 ,  A61K47/55

CPC classification number: A61K31/166 ,  A61K31/351 ,  A61K31/405 ,  A61K38/45 ,  A61K47/545 ,  A61K47/55 ,  A61K47/555 ,  A61P35/00 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  C12N9/1007 ,  C12Y201/01043

Abstract: 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.

公开(公告)号：US20230084249A1

公开(公告)日：2023-03-16

申请号：US17506324

申请日：2021-10-20

Applicant: Arvinas Operations, Inc.

Inventor： Michael Berlin ,  Andrew P. Crew ,  Hanqing Dong ,  Keith R. Hornberger ,  Lawrence B. Snyder ,  Jing Wang ,  Kurt Zimmermann

IPC: A61K47/54 ,  A61K45/06 ,  A61K47/64

Abstract: Bifunctional compounds, which find utility as modulators of androgen receptor (AR), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds AR, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

公开(公告)号：US20220395576A1

公开(公告)日：2022-12-15

申请号：US17721916

申请日：2022-04-15

Applicant: Arvinas Operations, Inc.

Inventor： Michael Berlin ,  Hanqing Dong ,  Dan Sherman ,  Lawrence B. Snyder ,  Jing Wang ,  Wei Zhang

IPC: A61K47/55 ,  A61K47/54 ,  A61K45/06 ,  A61P35/00

Abstract: Bifunctional compounds, which find utility as modulators of B-cell lymphoma 6 protein (BCL6; target protein), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a cereblon ligand that 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 bifunctional compounds of the present disclosure exhibit 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.

公开(公告)号：US20220378726A1

公开(公告)日：2022-12-01

申请号：US17354941

申请日：2021-06-22

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  Lawrence B. Snyder ,  Jing Wang ,  Hanqing Dong ,  Yimin Qian ,  Michael Berlin

IPC: A61K31/166 ,  A61K31/405 ,  A61K47/54 ,  A61P35/00 ,  A61K38/45 ,  C12N9/10 ,  A61K31/351 ,  C07D471/04 ,  C07D401/14 ,  C07D405/14 ,  C07D405/12 ,  C07D417/14 ,  C07D409/14 ,  A61K47/55

Abstract: 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.

公开(公告)号：US20210187108A1

公开(公告)日：2021-06-24

申请号：US16912329

申请日：2020-06-25

Applicant: Arvinas Operations, Inc. ,  Yale University

Inventor： Yimin Qian ,  Hanqing Dong ,  Jing Wang ,  Michael Berlin ,  Andrew P. Crew ,  Craig M. Crews

IPC: A61K45/06 ,  C07D519/00 ,  C07D417/14 ,  C07D495/14 ,  A61K47/55

Abstract: 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.