dc.contributor.author | Cheeseman, MD | |
dc.contributor.author | Chessum, NEA | |
dc.contributor.author | Rye, CS | |
dc.contributor.author | Pasqua, AE | |
dc.contributor.author | Tucker, MJ | |
dc.contributor.author | Wilding, B | |
dc.contributor.author | Evans, LE | |
dc.contributor.author | Lepri, S | |
dc.contributor.author | Richards, M | |
dc.contributor.author | Sharp, SY | |
dc.contributor.author | Ali, S | |
dc.contributor.author | Rowlands, M | |
dc.contributor.author | O'Fee, L | |
dc.contributor.author | Miah, A | |
dc.contributor.author | Hayes, A | |
dc.contributor.author | Henley, AT | |
dc.contributor.author | Powers, M | |
dc.contributor.author | Te Poele, R | |
dc.contributor.author | De Billy, E | |
dc.contributor.author | Pellegrino, L | |
dc.contributor.author | Raynaud, F | |
dc.contributor.author | Burke, R | |
dc.contributor.author | van Montfort, RLM | |
dc.contributor.author | Eccles, SA | |
dc.contributor.author | Workman, P | |
dc.contributor.author | Jones, K | |
dc.date.accessioned | 2016-12-12T13:29:53Z | |
dc.date.issued | 2017-01-12 | |
dc.identifier.citation | Journal of medicinal chemistry, 2017, 60 (1), pp. 180 - 201 | |
dc.identifier.issn | 0022-2623 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/320 | |
dc.identifier.eissn | 1520-4804 | |
dc.identifier.doi | 10.1021/acs.jmedchem.6b01055 | |
dc.description.abstract | Phenotypic screens, which focus on measuring and quantifying discrete cellular changes rather than affinity for individual recombinant proteins, have recently attracted renewed interest as an efficient strategy for drug discovery. In this article, we describe the discovery of a new chemical probe, bisamide (CCT251236), identified using an unbiased phenotypic screen to detect inhibitors of the HSF1 stress pathway. The chemical probe is orally bioavailable and displays efficacy in a human ovarian carcinoma xenograft model. By developing cell-based SAR and using chemical proteomics, we identified pirin as a high affinity molecular target, which was confirmed by SPR and crystallography. | |
dc.format | Print-Electronic | |
dc.format.extent | 180 - 201 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER CHEMICAL SOC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Amides | |
dc.subject | Quinolines | |
dc.subject | Carrier Proteins | |
dc.subject | DNA-Binding Proteins | |
dc.subject | Nuclear Proteins | |
dc.subject | Transcription Factors | |
dc.subject | Ligands | |
dc.subject | Spectrometry, Mass, Electrospray Ionization | |
dc.subject | Administration, Oral | |
dc.subject | Biological Availability | |
dc.subject | Drug Discovery | |
dc.subject | Proton Magnetic Resonance Spectroscopy | |
dc.subject | Carbon-13 Magnetic Resonance Spectroscopy | |
dc.subject | Heat Shock Transcription Factors | |
dc.title | Discovery of a Chemical Probe Bisamide (CCT251236): An Orally Bioavailable Efficacious Pirin Ligand from a Heat Shock Transcription Factor 1 (HSF1) Phenotypic Screen. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-11-23 | |
rioxxterms.versionofrecord | 10.1021/acs.jmedchem.6b01055 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2017-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Journal of medicinal chemistry | |
pubs.issue | 1 | |
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/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 3 | |
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/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 3 | |
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 | 60 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group) | |
icr.researchteam | Medicinal Chemistry 3 | |
icr.researchteam | Medicinal Chemistry 4 (including Analytical Chemistry) | |
icr.researchteam | Hit Discovery & Structural Design | |
dc.contributor.icrauthor | Cheeseman, Matthew | |
dc.contributor.icrauthor | Chessum, Nicola | |
dc.contributor.icrauthor | Richards, Gareth | |
dc.contributor.icrauthor | Ali, Salyha | |
dc.contributor.icrauthor | Raynaud, Florence | |
dc.contributor.icrauthor | Burke, Rosemary | |
dc.contributor.icrauthor | Van Montfort, Robert | |
dc.contributor.icrauthor | Workman, Paul | |
dc.contributor.icrauthor | Jones, Keith | |