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dc.contributor.authorFearon, D
dc.contributor.authorWestwood, IM
dc.contributor.authorvan Montfort, RLM
dc.contributor.authorBayliss, R
dc.contributor.authorJones, K
dc.contributor.authorBavetsias, V
dc.date.accessioned2018-05-23T13:11:38Z
dc.date.issued2018-07
dc.identifier.citationBioorganic & medicinal chemistry, 2018, 26 (11), pp. 3021 - 3029
dc.identifier.issn0968-0896
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1687
dc.identifier.eissn1464-3391
dc.identifier.doi10.1016/j.bmc.2018.04.033
dc.description.abstractScreening a 3-aminopyridin-2-one based fragment library against a 26-kinase panel representative of the human kinome identified 3-amino-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2(1H)-one (2) and 3-amino-5-(pyridin-4-yl)pyridin-2(1H)-one (3) as ligand efficient inhibitors of the mitotic kinase Monopolar Spindle 1 (MPS1) and the Aurora kinase family. These kinases are well recognised as attractive targets for therapeutic intervention for treating cancer. Elucidation of the binding mode of these fragments and their analogues has been carried out by X-ray crystallography. Structural studies have identified key interactions with a conserved lysine residue and have highlighted potential regions of MPS1 which could be targeted to improve activity and selectivity.
dc.formatPrint-Electronic
dc.format.extent3021 - 3029
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectAminopyridines
dc.subjectPeptide Fragments
dc.subjectPeptide Library
dc.subjectProtein Kinase Inhibitors
dc.subjectDrug Delivery Systems
dc.subjectCrystallography, X-Ray
dc.subjectInhibitory Concentration 50
dc.subjectMolecular Structure
dc.titleSynthesis and profiling of a 3-aminopyridin-2-one-based kinase targeted fragment library: Identification of 3-amino-5-(pyridin-4-yl)pyridin-2(1H)-one scaffold for monopolar spindle 1 (MPS1) and Aurora kinases inhibition.
dc.typeJournal Article
dcterms.dateAccepted2018-04-15
rioxxterms.versionofrecord10.1016/j.bmc.2018.04.033
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-07
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBioorganic & medicinal chemistry
pubs.issue11
pubs.notesNo embargo
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/Hit Discovery & Structural Design
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 1
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 3
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology/Hit Discovery & Structural Design
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/Hit Discovery & Structural Design
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 1
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 3
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology/Hit Discovery & Structural Design
pubs.publication-statusPublished
pubs.volume26en_US
pubs.embargo.termsNo embargo
icr.researchteamMedicinal Chemistry 1en_US
icr.researchteamMedicinal Chemistry 3en_US
icr.researchteamHit Discovery & Structural Designen_US
dc.contributor.icrauthorBavetsias, Vassiliosen
dc.contributor.icrauthorVan Montfort, Roberten
dc.contributor.icrauthorJones, Keithen


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