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dc.contributor.authorSimhadri, Chakravarthi
dc.contributor.authorDaze, Kevin D
dc.contributor.authorDouglas, Sarah F
dc.contributor.authorMilosevich, Natalia
dc.contributor.authorMonjas, Leticia
dc.contributor.authorDev, Amarjot
dc.contributor.authorBrown, Tyler M
dc.contributor.authorHirsch, Anna K H
dc.contributor.authorWulff, Jeremy E
dc.contributor.authorHof, Fraser
dc.date.accessioned2019-08-21T08:57:28Z
dc.date.available2019-08-21T08:57:28Z
dc.date.issued2019-08-06
dc.identifier.citationChemMedChem. 2019 Aug 6;14(15):1444-1456. doi: 10.1002/cmdc.201900021. Epub 2019en_US
dc.identifier.issn1860-7187
dc.identifier.pmid31254321
dc.identifier.doi10.1002/cmdc.201900021
dc.identifier.urihttp://hdl.handle.net/10033/621913
dc.description.abstractChromobox homolog 7 (Cbx7) is an epigenetic modulator that is an important driver of multiple cancers. It is a methyl reader protein that operates by recognizing and binding to methylated lysine residues on specific partners. Herein we report our efforts to create low-molecular-weight inhibitors of Cbx7 by making rational structural adaptations to inhibitors of a different methyl reader protein, L3MBTL1, inhibitors that had previously been reported to be inactive against Cbx7. We evaluated each new inhibitor for Cbx7 inhibition by fluorescence polarization assay, and also confirmed the binding of selected inhibitors to Cbx7 by saturation-transfer difference NMR spectroscopy. This work identified multiple small-molecule inhibitors with modest (IC50 : 257-500 μm) potency.en_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectanticancer agentsen_US
dc.subjectbromodomainsen_US
dc.subjectchromatinen_US
dc.subjectepigeneticsen_US
dc.subjecthistonesen_US
dc.titleRational Adaptation of L3MBTL1 Inhibitors to Create Small-Molecule Cbx7 Antagonists.en_US
dc.typeArticleen_US
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalChemMedChemen_US
dc.source.journaltitleChemMedChem


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