High resolution crystal structure of BRD4-BD1 in complex with a novel inhibitor precursor.
Biochem Biophys Res Commun
; 690: 149284, 2024 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-38006801
The inhibition of BRD4 bromodomain is an effective therapeutic strategy for a variety of diseases in which BRD4 are implicated. Herein, we identified a small-molecule BRD4 inhibitor hit named compound 3 using high-throughput screening. The 1.6 Å resolution co-crystal structure confirmed that the compound occupies the KAc recognition pockets of BRD4 by forming key hydrogen bonds with Asn140 and engaging in hydrophobic interactions, thus impedes the binding of acetylated lysine to BRD4. These findings suggest compound 3 can be a lead compound to develop a structurally novel BRD4 inhibitors.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Proteínas de Ciclo Celular
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2024
Tipo de documento:
Article