Activating mutations in leucine-rich repeat kinase 2 (LRRK2) are present in a subset of Parkinson's disease (PD) patients and may represent an attractive therapeutic target. Here we report a 2-anilino-4-methylamino-5-chloropyrimidine, HG-10-102-01(4) is a potent and selective inhibitor of wild-type LRRK2 and the G2019S mutant. Compound 4 substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant at a concentration of 0.1-0.3 microM in cells and is the first compound reported to be capable of inhibiting Ser910 and Ser935 phosphorylation in mouse brain following intraperitoneal delivery of doses as low as 50 mg/kg.
Author(s):
Choi, H. G., Zhang, J., Deng, X., Hatcher, J. M., Patricelli, M. P., Zhao, Z., Alessi, D. R., Gray, N. S.
PubMed:
23066449
Citation:
Choi, H. G., Zhang, J., Deng, X., Hatcher, J. M., Patricelli, M. P., Zhao, Z., Alessi, D. R., Gray, N. S.
Choi, H. G., Zhang, J., Deng, X., Hatcher, J. M., Patricelli, M. P., Zhao, Z., Alessi, D. R., Gray, N. S.
ACS Med Chem Lett
2012
3
658-662
PMID: 23066449