Characterization of TAE684 as a potent LRRK2 kinase inhibitor.
Bioorg Med Chem Lett
; 22(5): 1864-9, 2012 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-22335897
ABSTRACT
Leucine-rich repeat kinase 2 (LRRK2) is linked to Parkinson's disease and may represent an attractive therapeutic target. Here we report a 2,4-dianilino-5-chloro-pyrimidine, TAE684, a previously reported inhibitor of anaplastic lymphoma kinase (ALK), is also a potent inhibitor of LRRK2 kinase activity (IC(50) of 7.8nM against wild-type LRRK2, 6.1nM against the G2019S mutant). TAE684 substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant at a concentration of 0.1-0.3µM in cells and in mouse spleen and kidney, but not in brain, following oral doses of 10mg/kg.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Pirimidinas
/
Proteínas Serina-Treonina Quinases
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Reino Unido