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Differential mechanism of action of the CK1ε inhibitor GSD0054

2018Journal article Open access
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dc.contributor.authorLagunes, Irene
dc.contributor.authorMartín-Batista, Elva
dc.contributor.authorSilveira-Dorta, Gaston
dc.contributor.authorFernandes, Miguel X.
dc.contributor.authorPadrón, José M.
dc.date.accessioned2023-02-13T11:57:51Z
dc.date.available2023-02-13T11:57:51Z
dc.date.issued2018
dc.description.abstractIn the current study, we explored for the first time, the mechanism of action of the new Casein kinase 1 ε (CK1ε) selective inhibitor GSD0054. Although GSD0054 behaved as a selective CK1ε inhibitor in enzymatic assays, we studied whether this inhibitory activity also occurred inside the cells. The effects of GSD0054 on β-catenin expression and disruption of cell cycle progression were studied in the human breast cancer cell lines MDA-MB-453 (β-catenin negative) and T-47D (β-catenin positive). We also performed molecular modeling studies using computational docking against CK1ε to explain and predict the mechanism of action of this compound. Moreover, the commercially available CK1ε inhibitor PF-4800567 and the CK1δ/ε inhibitors PF-670462 and IC261 were also studied for comparison purposes. GSD0054 showed anti-proliferative activity against MDA-MB-453 and T-47D cells despite the fact that MDA-MB-453 cells do not possess active β-catenin. However, selective cell killing occurred in the more resistant, β-catenin active, T-47D cells. CK1ε was confirmed as a cellular target, although other targets or alternative mechanisms of action could possibly explain the anti-proliferative activity in MDA-MB-453 cells.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationLagunes, I., Martín-Batista, E., Silveira-Dorta, G., Fernandes, M. X., & Padrón, J. M. (2018). Differential mechanism of action of the CK1ε inhibitor GSD0054. Journal of Molecular and Clinical Medicine, 1(2), 77-84.pt_PT
dc.identifier.doi10.31083/j.jmcm.2018.02.004pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.13/5030
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherIMR Presspt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectSynthetic lethalitypt_PT
dc.subjectCasein kinase inhibitorspt_PT
dc.subjectWnt/beta-cateninpt_PT
dc.subjectAnti-beta-amino alcoholspt_PT
dc.subjectBreast cancerpt_PT
dc.subject.pt_PT
dc.subjectFaculdade de Ciências Exatas e da Engenhariapt_PT
dc.titleDifferential mechanism of action of the CK1ε inhibitor GSD0054pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage83pt_PT
oaire.citation.issue2pt_PT
oaire.citation.startPage77pt_PT
oaire.citation.titleJournal of Molecular and Clinical Medicinept_PT
oaire.citation.volume1pt_PT
person.familyNameFernandes
person.givenNameMiguel Xavier
person.identifier.ciencia-idED1D-3C7A-467C
person.identifier.orcid0000-0002-1840-616X
person.identifier.ridA-4373-2013
person.identifier.scopus-author-id35466972500
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication8dab9a0d-f44a-4d2d-b9b1-7b3145162ca3
relation.isAuthorOfPublication.latestForDiscovery8dab9a0d-f44a-4d2d-b9b1-7b3145162ca3

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