PubMed:23066449 JSONTXT

{"project":"PubTator4TogoVar","denotations":[{"id":"23066449_0","span":{"begin":458,"end":464},"obj":"ProteinMutation"},{"id":"23066449_1","span":{"begin":347,"end":353},"obj":"ProteinMutation"}],"attributes":[{"id":"23066449_0_ProteinMutation","pred":"proteinmutation","subj":"23066449_0","obj":"rs34637584"},{"id":"23066449_1_ProteinMutation","pred":"proteinmutation","subj":"23066449_1","obj":"rs34637584"}],"text":"Brain Penetrant LRRK2 Inhibitor.\nActivating 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 µM 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."}