dc.contributor.author | Rye, CS | |
dc.contributor.author | Chessum, NEA | |
dc.contributor.author | Lamont, S | |
dc.contributor.author | Pike, KG | |
dc.contributor.author | Faulder, P | |
dc.contributor.author | Demeritt, J | |
dc.contributor.author | Kemmitt, P | |
dc.contributor.author | Tucker, J | |
dc.contributor.author | Zani, L | |
dc.contributor.author | Cheeseman, MD | |
dc.contributor.author | Isaac, R | |
dc.contributor.author | Goodwin, L | |
dc.contributor.author | Boros, J | |
dc.contributor.author | Raynaud, F | |
dc.contributor.author | Hayes, A | |
dc.contributor.author | Henley, AT | |
dc.contributor.author | de Billy, E | |
dc.contributor.author | Lynch, CJ | |
dc.contributor.author | Sharp, SY | |
dc.contributor.author | Te Poele, R | |
dc.contributor.author | Fee, LO | |
dc.contributor.author | Foote, KM | |
dc.contributor.author | Green, S | |
dc.contributor.author | Workman, P | |
dc.contributor.author | Jones, K | |
dc.date.accessioned | 2016-09-21T10:46:34Z | |
dc.date.issued | 2016-08-01 | |
dc.identifier.citation | MedChemComm, 2016, 7 (8), pp. 1580 - 1586 | |
dc.identifier.issn | 2040-2503 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/120 | |
dc.identifier.eissn | 2040-2511 | |
dc.identifier.doi | 10.1039/c6md00159a | |
dc.description.abstract | Heat shock factor 1 (HSF1) is a transcription factor that plays key roles in cancer, including providing a mechanism for cell survival under proteotoxic stress. Therefore, inhibition of the HSF1-stress pathway represents an exciting new opportunity in cancer treatment. We employed an unbiased phenotypic screen to discover inhibitors of the HSF1-stress pathway. Using this approach we identified an initial hit (1) based on a 4,6-pyrimidine scaffold (2.00 μM). Optimisation of cellular SAR led to an inhibitor with improved potency (25, 15 nM) in the HSF1 phenotypic assay. The 4,6-pyrimidine 25 was also shown to have high potency against the CDK9 enzyme (3 nM). | |
dc.format | Print-Electronic | |
dc.format.extent | 1580 - 1586 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ROYAL SOC CHEMISTRY | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Discovery of 4,6-disubstituted pyrimidines as potent inhibitors of the heat shock factor 1 (HSF1) stress pathway and CDK9. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-06-07 | |
rioxxterms.versionofrecord | 10.1039/c6md00159a | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2016-08 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | MedChemComm | |
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/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 3 | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Sarcoma and Melanoma Surgery | |
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 3 | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Sarcoma and Melanoma Surgery | |
pubs.publication-status | Published | |
pubs.volume | 7 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group) | |
icr.researchteam | Medicinal Chemistry 3 | |
icr.researchteam | Sarcoma and Melanoma Surgery | |
dc.contributor.icrauthor | Cheeseman, Matthew | |
dc.contributor.icrauthor | Raynaud, Florence | |
dc.contributor.icrauthor | Workman, Paul | |
dc.contributor.icrauthor | Jones, Keith | |