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http://hdl.handle.net/10261/181174
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Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Venter, Jana | es_ES |
dc.contributor.author | Pérez, Concepción | es_ES |
dc.contributor.author | van Otterlo, Willem A. L. | es_ES |
dc.contributor.author | Martínez Gil, Ana | es_ES |
dc.contributor.author | Blackie, Margaret A.L. | es_ES |
dc.date.accessioned | 2019-05-09T12:48:26Z | - |
dc.date.available | 2019-05-09T12:48:26Z | - |
dc.date.issued | 2019-04-29 | - |
dc.identifier.citation | Bioorganic & Medicinal Chemistry Letters 29 (13)1597-1600 (2019) | es_ES |
dc.identifier.issn | 0960-894X | - |
dc.identifier.uri | http://hdl.handle.net/10261/181174 | - |
dc.description | 4 p.-4 fig.-1 tab. | es_ES |
dc.description.abstract | Glycogen 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.sponsorship | This 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.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-76693-R | es_ES |
dc.rights | closedAccess | es_ES |
dc.subject | Glycogen synthase kinase 3 | es_ES |
dc.subject | Alzheimer’s disease | es_ES |
dc.subject | Targeted covalent inhibitor | es_ES |
dc.subject | Cysteine 199 | es_ES |
dc.subject | Ureas | es_ES |
dc.title | 1-Aryl-3-(4-methoxybenzyl)ureas as potentially irreversible glycogen synthase kinase 3 inhibitors: Synthesis and biological evaluation | es_ES |
dc.type | artículo | es_ES |
dc.identifier.doi | 10.1016/j.bmcl.2019.04.049 | - |
dc.description.peerreviewed | No | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.bmcl.2019.04.049 | es_ES |
dc.identifier.e-issn | 1464-3405 | - |
dc.contributor.funder | National Research Foundation (South Africa) | es_ES |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | es_ES |
dc.relation.csic | Sí | es_ES |
oprm.item.hasRevision | no ko 0 false | * |
dc.identifier.funder | http://dx.doi.org/10.13039/501100003329 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100001321 | es_ES |
dc.contributor.orcid | Pérez, Concepción [0000-0001-7183-4035] | es_ES |
dc.contributor.orcid | van Otterlo, Willem A. L. [0000-0002-3300-6463] | es_ES |
dc.contributor.orcid | Martínez, Ana [0000-0002-2707-8110] | es_ES |
dc.contributor.orcid | Blackie, Margaret A.L. [0000-0002-2465-4987] | es_ES |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.grantfulltext | none | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | No Fulltext | - |
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