Publications | Characterization of TAE684 as a potent LRRK2 kinase inhibitor

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 0.1-0.3muM in cells and in mouse spleen and kidney, but not in brain, following oral doses of 10mg/kg.

Principal Investigator(s):

Author(s):
Zhang, J., Deng, X., Choi, H. G., Alessi, D. R., Gray, N. S.

PubMed:
22335897
Citation:
Zhang, J., Deng, X., Choi, H. G., Alessi, D. R., Gray, N. S.
Bioorg Med Chem Lett
2012
22
1864-1869
PMID: 22335897