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dc.contributor.authorKotev, Martin .
dc.contributor.authorManuel Manresa, Pilar .
dc.contributor.authorHernando Santa Cruz, Elsa 
dc.contributor.authorSoto Cerrato, Vanessa
dc.contributor.authorOrozco, Modesto .
dc.contributor.authorQuesada Pato, Roberto 
dc.contributor.authorPérez Tomás, Ricardo
dc.contributor.authorGuallar, Victor
dc.date.accessioned2018-08-24T09:48:45Z
dc.date.available2018-08-24T09:48:45Z
dc.date.issued2017-08
dc.identifier.issn1549-9596
dc.identifier.urihttp://hdl.handle.net/10259/4881
dc.description.abstractCombining computational modeling, de novo compound synthesis, and in vitro and cellular assays, we have performed an inhibition study against the enhancer of zeste homolog 2 (EZH2) histone-lysine N-methyltransferase. This enzyme is an important catalytic component of the PRC2 complex whose alterations have been associated with different cancers. We introduce here several tambjamine-inspired derivatives with low micromolar in vitro activity that produce a significant decrease in histone 3 trimethylation levels in cancer cells. We demonstrate binding at the methyl transfer active site, showing, in addition, that the EZH2 isolated crystal structure is capable of being used in molecular screening studies. Altogether, this work provides a successful molecular model that will help in the identification of new specific EZH2 inhibitors and identify a novel class of tambjamine-derived EZH2 inhibitors with promising activities for their use in cancer treatment.en
dc.description.sponsorshipSpanish Government (CTQ2016-79138-R; FIS PI13/00089), the Consejería de Educación de la Junta de Castilla y León (Projects BU340U13 and BU092U16), and from La Maratóde TV3 Foundation (20132730).en
dc.format.mimetypeapplication/pdf
dc.language.isoenges
dc.publisherAmerican Chemical Societyen
dc.relation.ispartofJournal of Chemical Information and Modeling. 2017, V. 57, n. 8, p. 2089-2098en
dc.subject.otherQuímica orgánicaes
dc.subject.otherChemistry, Organicen
dc.titleInhibition of human enhancer of zeste homolog 2 with tambjamine analogsen
dc.typeArtículoes
dc.typeinfo:eu-repo/semantics/article
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.relation.publisherversionhttps://doi.org/10.1021/acs.jcim.7b00178
dc.identifier.doi10.1021/acs.jcim.7b00178
dc.relation.projectIDinfo:eu-repo/grantAgreement/MICINN/CTQ2016-79138-R
dc.relation.projectIDinfo:eu-repo/grantAgreement/MSCBS/PI13-00089
dc.relation.projectIDinfo:eu-repo/grantAgreement/JCyL/BU340U13
dc.relation.projectIDinfo:eu-repo/grantAgreement/JCyL/BU092U16
dc.relation.projectIDinfo:eu-repo/grantAgreement/TV3Foundation/20132730
dc.type.hasVersioninfo:eu-repo/semantics/acceptedVersionen


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