Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 3, Issue 8, Pages 658-662Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ml300123a
Keywords
LRRK2; blood-brain barrier; brain penetrant inhibitor; 2,4-diaminopyrimidine
Categories
Funding
- NIH [P41 GM079575-03]
- Medical Research Council
- Michael J. Fox foundation for Parkinson's disease research
- AstraZeneca
- Boehringer-Ingelheim
- GlaxoSmithKline
- Merck KgaA
- Pfizer
- MRC [G0700656, MC_G1000735, MC_U127070193] Funding Source: UKRI
- Medical Research Council [G0700656, MC_G1000735, MC_U127070193] Funding Source: researchfish
Ask authors/readers for more resources
Activating mutations in leucine-rich repeat kinase 2 (LARK2) are present in a subset of Parkinson's disease (PD) patients and may represent an attractive therapeutic target. Here, we report that 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 mu M 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available