公开(公告)号：US20220276226A1

公开(公告)日：2022-09-01

申请号：US17631003

申请日：2020-07-28

Applicant: University of Houston System

Inventor： Alexander STATSYUK ,  Sandipan Roy CHOWDHURY

IPC: G01N33/50 ,  A61K47/55 ,  A61K47/54 ,  C07D417/14 ,  C07D401/14

Abstract: Multikinase degraders described herein contain on one end a Von Hippel-Lindau (VHL) E3 ligase ligand or cereblon E3 ligase recruiter moiety, which bind to the VHL or cereblon E3 ubiquitin ligase (defined as a ubiquitin ligand binding moiety or ULM group), respectively, and on the other end a promiscuous kinase ligand that binds a target protein kinase (defined as a protein/polypeptide targeting moiety or PTM group), such that the target protein is in close proximity to the ubiquitin ligase. This leads to the ubiquitination and subsequent degradation (and inhibition) of the target protein. Specific present multikinase degraders as shown bind about 360 out of 400 tested kinases, showing that they are much more general kinase binders and degraders than any previously reported.