Discovery of Tetrahydroquinoxalines as Bromodomain and Extra-Terminal Domain (BET) Inhibitors with Selectivity for the Second Bromodomain.
J Med Chem
; 61(10): 4317-4334, 2018 05 24.
Article
em En
| MEDLINE
| ID: mdl-29656650
ABSTRACT
The bromodomain and extra-terminal domain (BET) family of proteins bind acetylated lysine residues on histone proteins. The four BET bromodomains-BRD2, BRD3, BRD4, and BRDT-each contain two bromodomain modules. BET bromodomain inhibition is a potential therapy for various cancers and immunoinflammatory diseases, but few reported inhibitors show selectivity within the BET family. Inhibitors with selectivity for the first or second bromodomain are desired to aid investigation of the biological function of these domains. Focused library screening identified a series of tetrahydroquinoxalines with selectivity for the second bromodomains of the BET family (BD2). Structure-guided optimization of the template improved potency, selectivity, and physicochemical properties, culminating in potent BET inhibitors with BD2 selectivity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinoxalinas
/
Fatores de Transcrição
/
Proteínas Nucleares
/
Proteínas Serina-Treonina Quinases
/
Domínios e Motivos de Interação entre Proteínas
/
Descoberta de Drogas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Reino Unido