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dc.contributor.authorButler, Kyle V.-
dc.contributor.authorAnqi Ma-
dc.contributor.authorWenyu Yu-
dc.contributor.authorFengling Li-
dc.contributor.authorTempel, Wolfram-
dc.contributor.authorBabault, Nicolas-
dc.contributor.authorPittella-Silva, Fabio-
dc.contributor.authorShao, Jason-
dc.contributor.authorJunyi Wang-
dc.contributor.authorMinkui Luo-
dc.contributor.authorVedadi, Masoud-
dc.contributor.authorBrown, Peter J.-
dc.contributor.authorArrowsmith, Cheryl H.-
dc.contributor.authorJian Jin-
dc.date.accessioned2022-10-04T14:09:32Z-
dc.date.available2022-10-04T14:09:32Z-
dc.date.issued2016-
dc.identifier.citationBUTLER, Kyle V. et al. Structure-based design of a covalent Inhibitor of the SET domain-containing protein 8 (SETD8) lysine methyltransferase. Journal of Medicinal Chemistry, v. 59, 21, p. 9881–9889, 2016. DOI: https://doi.org/10.1021/acs.jmedchem.6b01244.pt_BR
dc.identifier.urihttps://repositorio.unb.br/handle/10482/44981-
dc.language.isoInglêspt_BR
dc.publisherAmerican Chemical Societypt_BR
dc.rightsAcesso Restritopt_BR
dc.titleStructure-based design of a covalent Inhibitor of the SET domain-containing protein 8 (SETD8) lysine methyltransferasept_BR
dc.typeArtigopt_BR
dc.subject.keywordAdutospt_BR
dc.subject.keywordEstrutura cristalinapt_BR
dc.subject.keywordInibidorespt_BR
dc.subject.keywordMonômerospt_BR
dc.subject.keywordPeptídeospt_BR
dc.subject.keywordProteínaspt_BR
dc.identifier.doihttps://doi.org/10.1021/acs.jmedchem.6b01244pt_BR
dc.relation.publisherversionhttps://pubs.acs.org/doi/10.1021/acs.jmedchem.6b01244#pt_BR
dc.description.abstract1Selective inhibitors of protein lysine methyltransferases, including SET domain-containing protein 8 (SETD8), are highly desired, as only a fraction of these enzymes are associated with high-quality inhibitors. From our previously discovered SETD8 inhibitor, we developed a more potent analog and solved a cocrystal structure, which is the first crystal structure of SETD8 in complex with a small-molecule inhibitor. This cocrystal structure allowed the design of a covalent inhibitor of SETD8 (MS453), which specifically modifies a cysteine residue near the inhibitor binding site, has an IC50 value of 804 nM, reacts with SETD8 with near-quantitative yield, and is selective for SETD8 against 28 other methyltransferases. We also solved the crystal structure of the covalent inhibitor in complex with SETD8. This work provides atomic-level perspective on the inhibition of SETD8 by small molecules and will help identify high-quality chemical probes of SETD8.pt_BR
dc.contributor.affiliationDepartment of Pharmacological Sciences and Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, Estados Unidospt_BR
dc.contributor.affiliationStructural Genomics Consortium, Universidade de Toronto, Toronto, Ontário M5G 1L7, Canadápt_BR
dc.contributor.affiliationMolecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, Estados Unidospt_BR
dc.contributor.affiliationDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, Ontário M5S 1A8, Canadápt_BR
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