dc.contributor.author | Vazquez-Rodriguez, S | |
dc.contributor.author | Wright, M | |
dc.contributor.author | Rogers, CM | |
dc.contributor.author | Cribbs, AP | |
dc.contributor.author | Velupillai, S | |
dc.contributor.author | Philpott, M | |
dc.contributor.author | Lee, H | |
dc.contributor.author | Dunford, JE | |
dc.contributor.author | Huber, KVM | |
dc.contributor.author | Robers, MB | |
dc.contributor.author | Vasta, JD | |
dc.contributor.author | Thezenas, M-L | |
dc.contributor.author | Bonham, S | |
dc.contributor.author | Kessler, B | |
dc.contributor.author | Bennett, J | |
dc.contributor.author | Fedorov, O | |
dc.contributor.author | Raynaud, F | |
dc.contributor.author | Donovan, A | |
dc.contributor.author | Blagg, J | |
dc.contributor.author | Bavetsias, V | |
dc.contributor.author | Oppermann, U | |
dc.contributor.author | Bountra, C | |
dc.contributor.author | Kawamura, A | |
dc.contributor.author | Brennan, PE | |
dc.date.accessioned | 2020-06-11T12:18:26Z | |
dc.date.issued | 2019-01-08 | |
dc.identifier.citation | Angewandte Chemie (International ed. in English), 2019, 58 (2), pp. 515 - 519 | |
dc.identifier.issn | 1433-7851 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3724 | |
dc.identifier.eissn | 1521-3773 | |
dc.identifier.doi | 10.1002/anie.201810179 | |
dc.description.abstract | Histone 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.format | Print-Electronic | |
dc.format.extent | 515 - 519 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | WILEY-V C H VERLAG GMBH | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Design, Synthesis and Characterization of Covalent KDM5 Inhibitors. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-10-15 | |
rioxxterms.versionofrecord | 10.1002/anie.201810179 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Angewandte Chemie (International ed. in English) | |
pubs.issue | 2 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 58 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group) | |
icr.researchteam | Medicinal Chemistry 1 | |
dc.contributor.icrauthor | Raynaud, Florence | |
dc.contributor.icrauthor | Bavetsias, Vassilios | |