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ID: ALA2010643

Journal: Bioorg Med Chem Lett

Title: Characterization of TAE684 as a potent LRRK2 kinase inhibitor.

Authors: Zhang J, Deng X, Choi HG, Alessi DR, Gray NS.

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.

CiteXplore: 22335897

DOI: 10.1016/j.bmcl.2012.01.084