dc.contributor.author | Innocenti, P | |
dc.contributor.author | Woodward, HL | |
dc.contributor.author | Solanki, S | |
dc.contributor.author | Naud, S | |
dc.contributor.author | Westwood, IM | |
dc.contributor.author | Cronin, N | |
dc.contributor.author | Hayes, A | |
dc.contributor.author | Roberts, J | |
dc.contributor.author | Henley, AT | |
dc.contributor.author | Baker, R | |
dc.contributor.author | Faisal, A | |
dc.contributor.author | Mak, GW-Y | |
dc.contributor.author | Box, G | |
dc.contributor.author | Valenti, M | |
dc.contributor.author | De Haven Brandon, A | |
dc.contributor.author | O'Fee, L | |
dc.contributor.author | Saville, H | |
dc.contributor.author | Schmitt, J | |
dc.contributor.author | Matijssen, B | |
dc.contributor.author | Burke, R | |
dc.contributor.author | van Montfort, RLM | |
dc.contributor.author | Raynaud, FI | |
dc.contributor.author | Eccles, SA | |
dc.contributor.author | Linardopoulos, S | |
dc.contributor.author | Blagg, J | |
dc.contributor.author | Hoelder, S | |
dc.date.accessioned | 2016-11-23T10:57:57Z | |
dc.date.issued | 2016-04-28 | |
dc.identifier.citation | Journal of medicinal chemistry, 2016, 59 (8), pp. 3671 - 3688 | |
dc.identifier.issn | 0022-2623 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/233 | |
dc.identifier.eissn | 1520-4804 | |
dc.identifier.doi | 10.1021/acs.jmedchem.5b01811 | |
dc.description.abstract | Monopolar spindle 1 (MPS1) plays a central role in the transition of cells from metaphase to anaphase and is one of the main components of the spindle assembly checkpoint. Chromosomally unstable cancer cells rely heavily on MPS1 to cope with the stress arising from abnormal numbers of chromosomes and centrosomes and are thus more sensitive to MPS1 inhibition than normal cells. We report the discovery and optimization of a series of new pyrido[3,4-d]pyrimidine based inhibitors via a structure-based hybridization approach from our previously reported inhibitor CCT251455 and a modestly potent screening hit. Compounds in this novel series display excellent potency and selectivity for MPS1, which translates into biomarker modulation in an in vivo human tumor xenograft model. | |
dc.format | Print-Electronic | |
dc.format.extent | 3671 - 3688 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER CHEMICAL SOC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Protein-Serine-Threonine Kinases | |
dc.subject | Cell Cycle Proteins | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Molecular Structure | |
dc.subject | Protein-Tyrosine Kinases | |
dc.subject | Drug Discovery | |
dc.title | Rapid Discovery of Pyrido[3,4-d]pyrimidine Inhibitors of Monopolar Spindle Kinase 1 (MPS1) Using a Structure-Based Hybridization Approach. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-03-01 | |
rioxxterms.versionofrecord | 10.1021/acs.jmedchem.5b01811 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2016-04-07 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Journal of medicinal chemistry | |
pubs.issue | 8 | |
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/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Drug Target Discovery | |
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/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 4 (including Analytical Chemistry) | |
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/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Drug Target Discovery | |
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/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 4 (including Analytical Chemistry) | |
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 | 59 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Drug Target Discovery | |
icr.researchteam | Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group) | |
icr.researchteam | Medicinal Chemistry 1 | |
icr.researchteam | Medicinal Chemistry 4 (including Analytical Chemistry) | |
icr.researchteam | Hit Discovery & Structural Design | |
dc.contributor.icrauthor | Burke, Rosemary | |
dc.contributor.icrauthor | Van Montfort, Robert | |
dc.contributor.icrauthor | Raynaud, Florence | |
dc.contributor.icrauthor | Linardopoulos, Spyridon | |
dc.contributor.icrauthor | Hoelder, Swen | |