The kinetics of binding to p38MAP kinase by analogues of BIRB 796.
Bioorg Med Chem Lett
; 13(18): 3101-4, 2003 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-12941343
ABSTRACT
BIRB 796, a member of the N-pyrazole-N'-naphthly urea class of p38MAPK inhibitors, binds to the kinase with both slow association and dissociation rates. Prior to binding, the kinase undergoes a reorganization of the activation loop exposing a critical binding domain. We demonstrate that, independent of the loop movement, association rates are governed by low energy conformations of the inhibitor and polar functionality on the tolyl ring. As anticipated, the dissociation rates of the inhibitors from the kinase are slowed by lipophilic and hydrogen bond interactions. The value of structure-kinetic relationships (SKR) in drug design is discussed.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Proteínas Quinases Ativadas por Mitógeno
/
Inibidores Enzimáticos
/
Naftalenos
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos