Targeting the deubiquitinase USP7 for degradation with PROTACs.
Chem Commun (Camb)
; 58(63): 8858-8861, 2022 Aug 04.
Article
em En
| MEDLINE
| ID: mdl-35852517
ABSTRACT
Targeting deubiquitinating enzymes (DUBs) has emerged as a promising therapeutic approach in several human cancers and other diseases. DUB inhibitors are exciting pharmacological tools but often exhibit limited cellular potency. Here we report PROTACs based on a ubiquitin-specific protease 7 (USP7) inhibitor scaffold to degrade USP7. By investigating several linker and E3 ligand types, including novel cereblon recruiters, we discovered a highly selective USP7 degrader tool compound that induced apoptosis of USP7-dependent cancer cells. This work represents one of the first DUB degraders and unlocks a new drug target class for protein degradation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos e Proteínas de Sinalização Intercelular
/
Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Chem Commun (Camb)
Ano de publicação:
2022
Tipo de documento:
Article