dc.contributor.author | Fearon, D | |
dc.contributor.author | Westwood, IM | |
dc.contributor.author | van Montfort, RLM | |
dc.contributor.author | Bayliss, R | |
dc.contributor.author | Jones, K | |
dc.contributor.author | Bavetsias, V | |
dc.date.accessioned | 2018-05-23T13:11:38Z | |
dc.date.issued | 2018-07-15 | |
dc.identifier.citation | Bioorganic & medicinal chemistry, 2018, 26 (11), pp. 3021 - 3029 | |
dc.identifier.issn | 0968-0896 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1687 | |
dc.identifier.eissn | 1464-3391 | |
dc.identifier.doi | 10.1016/j.bmc.2018.04.033 | |
dc.description.abstract | Screening 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.format | Print-Electronic | |
dc.format.extent | 3021 - 3029 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Aminopyridines | |
dc.subject | Peptide Fragments | |
dc.subject | Peptide Library | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Drug Delivery Systems | |
dc.subject | Crystallography, X-Ray | |
dc.subject | Inhibitory Concentration 50 | |
dc.subject | Molecular Structure | |
dc.title | Synthesis 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.type | Journal Article | |
dcterms.dateAccepted | 2018-04-15 | |
rioxxterms.versionofrecord | 10.1016/j.bmc.2018.04.033 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-07 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Bioorganic & medicinal chemistry | |
pubs.issue | 11 | |
pubs.notes | No 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-status | Published | |
pubs.volume | 26 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Medicinal Chemistry 1 | |
icr.researchteam | Medicinal Chemistry 3 | |
icr.researchteam | Hit Discovery & Structural Design | |
dc.contributor.icrauthor | Van Montfort, Robert | |
dc.contributor.icrauthor | Jones, Keith | |
dc.contributor.icrauthor | Bavetsias, Vassilios | |