GSK2578215A; A potent and highly selective 2-arylmethyloxy-5-substitutent- N-arylbenzamide LRRK2 kinase inhibitor
dc.contributor.author | Reith, AD | |
dc.contributor.author | Bamborough, P | |
dc.contributor.author | Jandu, K | |
dc.contributor.author | Andreotti, D | |
dc.contributor.author | Mensah, L | |
dc.contributor.author | Dossang, P | |
dc.contributor.author | Choi, HG | |
dc.contributor.author | Deng, X | |
dc.contributor.author | Zhang, J | |
dc.contributor.author | Alessi, DR | |
dc.contributor.author | Gray, NS | |
dc.date.accessioned | 2019-01-30T15:12:19Z | |
dc.date.issued | 2012-07-07 | |
dc.description.abstract | Leucine-rich repeat kinase 2 (LRRK2) is a promising therapeutic target for some forms of Parkinson's disease. Here we report the discovery and characterization of 2-arylmethyloxy-5-subtitutent-N-arylbenzamides with potent LRRK2 activities exemplified by GSK2578215A which exhibits biochemical IC 50s of around 10 nM against both wild-type LRRK2 and the G2019S mutant. GSK2578215A exhibits exceptionally high selectivity for LRRK2 across the kinome, substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant at a concentration of 0.3-1.0 μM in cells and in mouse spleen and kidney, but not in brain, following intraperitoneal injection of 100 mg/kg. © 2012 Elsevier Ltd. All rights reserved. | en_GB |
dc.description.sponsorship | Michael J. Fox Foundation for Parkinson’s Research | en_GB |
dc.description.sponsorship | National Institutes of Health (NIH) | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.identifier.citation | Vol. 22 (17), pp. 5625 - 5629 | en_GB |
dc.identifier.doi | 10.1016/j.bmcl.2012.06.104 | |
dc.identifier.grantnumber | P41 GM079575-03 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/35665 | |
dc.language.iso | en | en_GB |
dc.publisher | Elsevier | en_GB |
dc.rights | © 2012. This version is made available under the CC-BY-NC-ND 4.0 license: https://creativecommons.org/licenses/by-nc-nd/4.0/ | en_GB |
dc.subject | LRRK2 | en_GB |
dc.subject | Drug discovery | en_GB |
dc.subject | Kinase inhibitors | en_GB |
dc.subject | Parkinson’s disease | en_GB |
dc.title | GSK2578215A; A potent and highly selective 2-arylmethyloxy-5-substitutent- N-arylbenzamide LRRK2 kinase inhibitor | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-01-30T15:12:19Z | |
dc.identifier.issn | 0960-894X | |
dc.description | This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record | en_GB |
dc.identifier.journal | Bioorganic and Medicinal Chemistry Letters | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | en_GB |
dcterms.dateAccepted | 2012-06-29 | |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2012-06-29 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-01-30T15:07:48Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2019-01-30T15:12:23Z | |
refterms.panel | A | en_GB |
Files in this item
This item appears in the following Collection(s)
Except where otherwise noted, this item's licence is described as © 2012. This version is made available under the CC-BY-NC-ND 4.0 license: https://creativecommons.org/licenses/by-nc-nd/4.0/