Pyridyl aminothiazoles as potent inhibitors of Chk1 with slow dissociation rates.
Bioorg Med Chem Lett
; 22(7): 2609-12, 2012 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-22374217
ABSTRACT
Pyridyl aminothiazoles comprise a novel class of ATP-competitive Chk1 inhibitors with excellent inhibitory potential. Modification of the core with ethylenediamine amides provides compounds with low picomolar potency and very high residence times. Investigation of binding parameters of such compounds using X-ray crystallography and molecular dynamics simulations revealed multiple hydrogen bonds to the enzyme backbone as well as stabilization of the conserved water molecules network in the hydrophobic binding region.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
/
Piridinas
/
Tiazóis
/
Inibidores de Proteínas Quinases
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos