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dc.contributor.authorVenter, Janaes_ES
dc.contributor.authorPérez, Concepciónes_ES
dc.contributor.authorvan Otterlo, Willem A. L.es_ES
dc.contributor.authorMartínez Gil, Anaes_ES
dc.contributor.authorBlackie, Margaret A.L.es_ES
dc.date.accessioned2019-05-09T12:48:26Z-
dc.date.available2019-05-09T12:48:26Z-
dc.date.issued2019-04-29-
dc.identifier.citationBioorganic & Medicinal Chemistry Letters 29 (13)1597-1600 (2019)es_ES
dc.identifier.issn0960-894X-
dc.identifier.urihttp://hdl.handle.net/10261/181174-
dc.description4 p.-4 fig.-1 tab.es_ES
dc.description.abstractGlycogen synthase kinase 3 (GSK-3) has become known for its multifactorial involvement in the pathogenesis of Alzheimer’s disease. In this study, a benzothiazole- and benzimidazole set of 1-aryl-3-(4-methoxybenzyl)ureas were synthesised as proposed Cys199-targeted covalent inhibitors of GSK-3β, through the incorporation of an electrophilic warhead onto their ring scaffolds. The nitrile-substituted benzimidazolylurea 2b (IC50 = 0.086 ± 0.023 µM) and halomethylketone-substituted benzimidazolylurea 9b (IC50 = 0.13 ± 0.060 µM) displayed high GSK-3β inhibitory activity, in comparison to reference inhibitor AR-A014418 (1, IC50 = 0.072 ± 0.043) in our assay. The results suggest further investigation of 2b and 9b as potential covalent inhibitors of GSK-3β, since a targeted interaction might provide improved kinase-selectivity.es_ES
dc.description.sponsorshipThis research was financially supported by the National Research Foundation, South Africa (Innovation Master’s Scholarship 2017–2018), Stellenbosch University and MINECO (Grant No. SAF2016-76693-R).es_ES
dc.language.isoenges_ES
dc.publisherElsevieres_ES
dc.relationinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-76693-Res_ES
dc.rightsclosedAccesses_ES
dc.subjectGlycogen synthase kinase 3es_ES
dc.subjectAlzheimer’s diseasees_ES
dc.subjectTargeted covalent inhibitores_ES
dc.subjectCysteine 199es_ES
dc.subjectUreases_ES
dc.title1-Aryl-3-(4-methoxybenzyl)ureas as potentially irreversible glycogen synthase kinase 3 inhibitors: Synthesis and biological evaluationes_ES
dc.typeartículoes_ES
dc.identifier.doi10.1016/j.bmcl.2019.04.049-
dc.description.peerreviewedNoes_ES
dc.relation.publisherversionhttps://doi.org/10.1016/j.bmcl.2019.04.049es_ES
dc.identifier.e-issn1464-3405-
dc.contributor.funderNational Research Foundation (South Africa)es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.relation.csices_ES
oprm.item.hasRevisionno ko 0 false*
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003329es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100001321es_ES
dc.contributor.orcidPérez, Concepción [0000-0001-7183-4035]es_ES
dc.contributor.orcidvan Otterlo, Willem A. L. [0000-0002-3300-6463]es_ES
dc.contributor.orcidMartínez, Ana [0000-0002-2707-8110]es_ES
dc.contributor.orcidBlackie, Margaret A.L. [0000-0002-2465-4987]es_ES
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.openairetypeartículo-
item.cerifentitytypePublications-
item.languageiso639-1en-
item.grantfulltextnone-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextNo Fulltext-
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