Development of the first geldanamycin-based HSP90 degraders.
Front Chem
; 11: 1219883, 2023.
Article
em En
| MEDLINE
| ID: mdl-37448856
ABSTRACT
Despite the early clinical promise, adverse events such as acquired resistance and dose-limiting toxicities have barred the widespread use of HSP90 inhibitors as anticancer drugs. A new approach involving proteolysis-targeting chimeras (PROTACs) to degrade the protein instead of inhibiting it may overcome these problems. In this work, we describe the design, synthesis, and evaluation of cereblon-recruiting geldanamycin-based HSP90 degraders based on the PROTAC technology. Our best degrader, 3a, effectively decreased HSP90α and HSP90ß levels in cells utilizing the ubiquitin-proteasome pathway.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Front Chem
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Alemanha