Discovery of spirohydantoins as selective, orally bioavailable inhibitors of p300/CBP histone acetyltransferases.
Bioorg Med Chem Lett
; 39: 127854, 2021 05 01.
Article
en En
| MEDLINE
| ID: mdl-33631370
ABSTRACT
p300 and CREB-binding protein (CBP) are essential for a multitude of cellular processes. Dysregulation of p300/CBP histone acetyltransferase activity is linked to a broad spectrum of human diseases including cancers. A novel drug-like spirohydantoin (21) has been discovered as a selective orally bioavailable inhibitor of p300/CBP histone acetyltransferase. Lead compound 21 is more potent than the first-in-class lead A-485 in both enzymatic and cellular assays and lacks the off-target inhibition of dopamine and serotonin transporters, that was observed with A-485.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Compuestos de Espiro
/
Inhibidores Enzimáticos
/
Proteína de Unión a CREB
/
Proteína p300 Asociada a E1A
/
Descubrimiento de Drogas
/
Hidantoínas
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2021
Tipo del documento:
Article