Covalent-Allosteric Kinase Inhibitors.
Angew Chem Int Ed Engl
; 54(35): 10313-6, 2015 Aug 24.
Article
em En
| MEDLINE
| ID: mdl-26110718
ABSTRACT
Targeting and stabilizing distinct kinase conformations is an instrumental strategy for dissecting conformation-dependent signaling of protein kinases. Herein the structure-based design, synthesis, and evaluation of pleckstrin homology (PH) domain-dependent covalent-allosteric inhibitors (CAIs) of the kinase Akt is reported. These inhibitors bind covalently to a distinct cysteine of the kinase and thereby stabilize the inactive kinase conformation. These modulators exhibit high potency and selectivity, and represent an innovative approach for chemical biology and medicinal chemistry research.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Inibidores de Proteínas Quinases
/
Proteínas Proto-Oncogênicas c-akt
Limite:
Humans
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2015
Tipo de documento:
Article