dc.contributor.author | Choi, Hwan Geun | |
dc.contributor.author | Zhang, Jin-Wei | |
dc.contributor.author | Deng, Xianming | |
dc.contributor.author | Hatcher, JM | |
dc.contributor.author | Patricelli, MP | |
dc.contributor.author | Zhao, Z | |
dc.contributor.author | Alessi, DR | |
dc.contributor.author | Gray, NS | |
dc.date.accessioned | 2019-02-11T13:50:51Z | |
dc.date.issued | 2012-06-18 | |
dc.description.abstract | 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 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 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. © 2012 American Chemical Society. | en_GB |
dc.description.sponsorship | NIH | en_GB |
dc.description.sponsorship | Medical Research Council | en_GB |
dc.description.sponsorship | Michael J Fox foundation for Parkinson’s disease research | en_GB |
dc.description.sponsorship | Pharmaceutical companies supporting the DSTT (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KgaA and Pfizer) | en_GB |
dc.identifier.citation | Vol. 3 (8), pp. 658 - 662 | en_GB |
dc.identifier.doi | 10.1021/ml300123a | |
dc.identifier.grantnumber | P41 GM079575-03 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/35896 | |
dc.language.iso | en | en_GB |
dc.publisher | American Chemical Society | en_GB |
dc.rights | © 2012 American Chemical Society | en_GB |
dc.subject | LRRK2 | en_GB |
dc.subject | Blood-brain barrier | en_GB |
dc.subject | Brain Penetrant Inhibitor | en_GB |
dc.subject | 2,4-diaminopyrimidine | en_GB |
dc.title | Brain penetrant LRRK2 inhibitor | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-02-11T13:50:51Z | |
dc.identifier.issn | 1948-5875 | |
dc.description | This is the author accepted manuscript. The final version is available from ACS via the DOI in this record. | en_GB |
dc.identifier.journal | ACS Medicinal Chemistry Letters | en_GB |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | en_GB |
dcterms.dateAccepted | 2012-06-18 | |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2012-06-18 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-02-11T13:46:06Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2019-02-11T13:50:55Z | |
refterms.panel | A | en_GB |