Discovery of a potent and selective CBP bromodomain inhibitor (Y08262) for treating acute myeloid leukemia.
Bioorg Chem
; 142: 106950, 2024 01.
Article
en En
| MEDLINE
| ID: mdl-37924753
ABSTRACT
The bromodomain of CREB (cyclic-AMP response element binding protein) binding protein (CBP) is an epigenetic "reader" and plays a key role in transcriptional regulation. CBP bromodomain is considered to be a promising therapeutic target for acute myeloid leukemia (AML). Herein, we report the discovery of a series of 1-(indolizin-3-yl)ethan-1-one derivatives as potent, and selective CBP bromodomain inhibitors focused on improving cellular potency. One of the most promising compounds, 7e (Y08262), inhibits the CBP bromodomain at the nanomolar level (IC50 = 73.1 nM) with remarkable selectivity. In addition, the new inhibitor also displays potent inhibitory activities in AML cell lines. Collectively, this study provides a new lead compound for further validation of CBP bromodomain as a molecular target for AML drug development.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Leucemia Mieloide Aguda
Límite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Año:
2024
Tipo del documento:
Article