Bardoxolone conjugation enables targeted protein degradation of BRD4.
Sci Rep
; 10(1): 15543, 2020 09 23.
Article
em En
| MEDLINE
| ID: mdl-32968148
ABSTRACT
Targeted protein degradation (TPD) has emerged as a powerful tool in drug discovery for the perturbation of protein levels using heterobifunctional small molecules. E3 ligase recruiters remain central to this process yet relatively few have been identified relative to the ~ 600 predicted human E3 ligases. While, initial recruiters have utilized non-covalent chemistry for protein binding, very recently covalent engagement to novel E3's has proven fruitful in TPD application. Herein we demonstrate efficient proteasome-mediated degradation of BRD4 by a bifunctional small molecule linking the KEAP1-Nrf2 activator bardoxolone to a BRD4 inhibitor JQ1.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Oleanólico
/
Fatores de Transcrição
/
Proteínas de Ciclo Celular
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos