Discovery of BAZ1A bromodomain inhibitors with the aid of virtual screening and activity evaluation.
Bioorg Med Chem Lett
; 33: 127745, 2021 02 01.
Article
en En
| MEDLINE
| ID: mdl-33333161
ABSTRACT
BAZ1A is a bromodomain-containing protein, and has been recognized as a potential target for multiple diseases, particularly cancer. However, there is no BAZ1A inhibitor reported so far. In this study, we used a consensus docking/scoring strategy to screen for BAZ1A bromodomain inhibitors from commercial chemical libraries and an in-house chemical database. The retrieved hit compounds were evaluated experimentally and four compounds were found to be active against BAZ1A bromodomain. To the most active compounds, similarity and substructure searches were used to find more BAZ1A bromodomain inhibitors. Among all the obtained active compounds, Cpd-2 is the most potent one, which showed a KD value of 0.52 µM. The interaction model of Cpd-2 with BAZ1A bromodomain was revealed by molecular docking. In a cellular assay, Cpd-2 displayed good anti-viability activity against cancer cell lines expressing a high level of BAZ1A. Overall, we discovered a number of BAZ1A bromodomain inhibitors for the first time, which can be a good starting point for subsequent drug discovery targeting BAZ1A bromodomain.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Compuestos Orgánicos
/
Proteínas Cromosómicas no Histona
/
Descubrimiento de Drogas
/
Antineoplásicos
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos