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dc.contributor.authorReith, AD
dc.contributor.authorBamborough, P
dc.contributor.authorJandu, K
dc.contributor.authorAndreotti, D
dc.contributor.authorMensah, L
dc.contributor.authorDossang, P
dc.contributor.authorChoi, HG
dc.contributor.authorDeng, X
dc.contributor.authorZhang, J
dc.contributor.authorAlessi, DR
dc.contributor.authorGray, NS
dc.date.accessioned2019-01-30T15:12:19Z
dc.date.issued2012-07-07
dc.description.abstractLeucine-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.sponsorshipMichael J. Fox Foundation for Parkinson’s Researchen_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipMedical Research Council (MRC)en_GB
dc.identifier.citationVol. 22 (17), pp. 5625 - 5629en_GB
dc.identifier.doi10.1016/j.bmcl.2012.06.104
dc.identifier.grantnumberP41 GM079575-03en_GB
dc.identifier.urihttp://hdl.handle.net/10871/35665
dc.language.isoenen_GB
dc.publisherElsevieren_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.subjectLRRK2en_GB
dc.subjectDrug discoveryen_GB
dc.subjectKinase inhibitorsen_GB
dc.subjectParkinson’s diseaseen_GB
dc.titleGSK2578215A; A potent and highly selective 2-arylmethyloxy-5-substitutent- N-arylbenzamide LRRK2 kinase inhibitoren_GB
dc.typeArticleen_GB
dc.date.available2019-01-30T15:12:19Z
dc.identifier.issn0960-894X
dc.description This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recorden_GB
dc.identifier.journalBioorganic and Medicinal Chemistry Lettersen_GB
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/  en_GB
dcterms.dateAccepted2012-06-29
rioxxterms.versionAMen_GB
rioxxterms.licenseref.startdate2012-06-29
rioxxterms.typeJournal Article/Reviewen_GB
refterms.dateFCD2019-01-30T15:07:48Z
refterms.versionFCDAM
refterms.dateFOA2019-01-30T15:12:23Z
refterms.panelAen_GB


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© 2012. This version is made available under the CC-BY-NC-ND 4.0 license: https://creativecommons.org/licenses/by-nc-nd/4.0/  
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/