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dc.contributor.authorVazquez-Rodriguez, S
dc.contributor.authorWright, M
dc.contributor.authorRogers, CM
dc.contributor.authorCribbs, AP
dc.contributor.authorVelupillai, S
dc.contributor.authorPhilpott, M
dc.contributor.authorLee, H
dc.contributor.authorDunford, JE
dc.contributor.authorHuber, KVM
dc.contributor.authorRobers, MB
dc.contributor.authorVasta, JD
dc.contributor.authorThezenas, M-L
dc.contributor.authorBonham, S
dc.contributor.authorKessler, B
dc.contributor.authorBennett, J
dc.contributor.authorFedorov, O
dc.contributor.authorRaynaud, F
dc.contributor.authorDonovan, A
dc.contributor.authorBlagg, J
dc.contributor.authorBavetsias, V
dc.contributor.authorOppermann, U
dc.contributor.authorBountra, C
dc.contributor.authorKawamura, A
dc.contributor.authorBrennan, PE
dc.date.accessioned2020-06-11T12:18:26Z
dc.date.issued2019-01-08
dc.identifier.citationAngewandte Chemie (International ed. in English), 2019, 58 (2), pp. 515 - 519
dc.identifier.issn1433-7851
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3724
dc.identifier.eissn1521-3773
dc.identifier.doi10.1002/anie.201810179
dc.description.abstractHistone lysine demethylases (KDMs) are involved in the dynamic regulation of gene expression and they play a critical role in several biological processes. Achieving selectivity over the different KDMs has been a major challenge for KDM inhibitor development. Here we report potent and selective KDM5 covalent inhibitors designed to target cysteine residues only present in the KDM5 sub-family. The covalent binding to the targeted proteins was confirmed by MS and time-dependent inhibition. Additional competition assays show that compounds were non 2-OG competitive. Target engagement and ChIP-seq analysis showed that the compounds inhibited the KDM5 members in cells at nano- to micromolar levels and induce a global increase of the H3K4me3 mark at transcriptional start sites.
dc.formatPrint-Electronic
dc.format.extent515 - 519
dc.languageeng
dc.language.isoeng
dc.publisherWILEY-V C H VERLAG GMBH
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleDesign, Synthesis and Characterization of Covalent KDM5 Inhibitors.
dc.typeJournal Article
dcterms.dateAccepted2018-10-15
rioxxterms.versionofrecord10.1002/anie.201810179
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfAngewandte Chemie (International ed. in English)
pubs.issue2
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 1
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 1
pubs.publication-statusPublished
pubs.volume58
pubs.embargo.termsNot known
icr.researchteamClinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
icr.researchteamMedicinal Chemistry 1
dc.contributor.icrauthorRaynaud, Florence
dc.contributor.icrauthorBavetsias, Vassilios


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Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0