Pyrrolopyridine inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2).
J Med Chem
; 50(11): 2647-54, 2007 May 31.
Article
em En
| MEDLINE
| ID: mdl-17480064
ABSTRACT
A new class of potent kinase inhibitors selective for mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2 or MK-2) for the treatment of rheumatoid arthritis has been prepared and evaluated. These inhibitors have IC50 values as low as 10 nM against the target and have good selectivity profiles against a number of kinases including CDK2, ERK, JNK, and p38. These MK-2 inhibitors have been shown to suppress TNFalpha production in U397 cells and to be efficacious in an acute inflammation model. The structure-activity relationships of this series, the selectivity for MK-2 and their activity in both in vitro and in vivo models are discussed. The observed selectivity is discussed with the aid of an MK-2/inhibitor crystal structure.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piridinas
/
Pirróis
/
Anti-Inflamatórios não Esteroides
/
Proteínas Serina-Treonina Quinases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos