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：US11584743B2

公开(公告)日：2023-02-21

申请号：US17082839

申请日：2020-10-28

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  Yimin Qian ,  Hanging Dong ,  Jing Wang

IPC: C07D417/14 ,  C07K5/062 ,  C07D403/12 ,  C07D403/14 ,  C07D413/14

Abstract: The present disclosure relates to compounds and a pharmaceutically acceptable salt thereof, compositions, combinations and medicaments containing the compounds, and processes for their preparation. The disclosure also relates to the use of the compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of the estrogen receptor, including degrading the estrogen receptor, the treatment of diseases and conditions mediated by the estrogen receptor.

公开(公告)号：US20210315856A1

公开(公告)日：2021-10-14

申请号：US17356751

申请日：2021-06-24

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  Hanging Dong ,  Brain Hamman ,  Taavi K. Neklesa ,  Yimin Qian ,  Jing Wang ,  Kurt Zimmermann

IPC: A61K31/277 ,  G16B20/00 ,  A61K47/55 ,  G16C20/50 ,  G16B15/30 ,  G16B20/30 ,  A61K31/4166 ,  A61K31/551 ,  A61K38/05 ,  G01N33/68

Abstract: The present disclosure is based on the surprising and unexpected discovery that a ligand molecule with certain characteristics is able to bind to two protein molecules simultaneously and recruit them to form a transient or stable protein-protein interaction complex. The protein-protein interaction and other cross-domain interactions gained in this process contribute additional stabilization energy to the complex beyond the combination of the binary binding energies, and therefore, largely increase the binding potency of the ligand. Accordingly, the present disclosure provides a Protein-Protein Interaction Inducing Technology (PPIIT), which includes a method to design and identify the tripartite or bifunctional compounds and use such compounds to induce protein-protein interactions in various contexts. The present disclosure also provides a composition for the purpose of inducing protein-protein interactions.