Structure-based design of isoquinoline-5-sulfonamide inhibitors of protein kinase B.
Bioorg Med Chem
; 14(4): 1255-73, 2006 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-16249095
ABSTRACT
Structure-based drug design of novel isoquinoline-5-sulfonamide inhibitors of PKB as potential antitumour agents was investigated. Constrained pyrrolidine analogues that mimicked the bound conformation of linear prototypes were identified and investigated by co-crystal structure determinations with the related protein PKA. Detailed variation in the binding modes between inhibitors with similar overall conformations was observed. Potent PKB inhibitors from this series inhibited GSK3beta phosphorylation in cellular assays, consistent with inhibition of PKB kinase activity in cells.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
/
Desenho de Fármacos
/
Inibidores de Proteínas Quinases
/
Proteínas Proto-Oncogênicas c-akt
/
Isoquinolinas
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Ano de publicação:
2006
Tipo de documento:
Article