dc.contributor.author | Cheeseman, MD | |
dc.contributor.author | Westwood, IM | |
dc.contributor.author | Barbeau, O | |
dc.contributor.author | Rowlands, M | |
dc.contributor.author | Dobson, S | |
dc.contributor.author | Jones, AM | |
dc.contributor.author | Jeganathan, F | |
dc.contributor.author | Burke, R | |
dc.contributor.author | Kadi, N | |
dc.contributor.author | Workman, P | |
dc.contributor.author | Collins, I | |
dc.contributor.author | van Montfort, RLM | |
dc.contributor.author | Jones, K | |
dc.date.accessioned | 2016-11-24T14:04:56Z | |
dc.date.issued | 2016-05-26 | |
dc.identifier.citation | Journal of medicinal chemistry, 2016, 59 (10), pp. 4625 - 4636 | |
dc.identifier.issn | 0022-2623 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/286 | |
dc.identifier.eissn | 1520-4804 | |
dc.identifier.doi | 10.1021/acs.jmedchem.5b02001 | |
dc.description.abstract | HSP70 is a molecular chaperone and a key component of the heat-shock response. Because of its proposed importance in oncology, this protein has become a popular target for drug discovery, efforts which have as yet brought little success. This study demonstrates that adenosine-derived HSP70 inhibitors potentially bind to the protein with a novel mechanism of action, the stabilization by desolvation of an intramolecular salt-bridge which induces a conformational change in the protein, leading to high affinity ligands. We also demonstrate that through the application of this mechanism, adenosine-derived HSP70 inhibitors can be optimized in a rational manner. | |
dc.format | Print-Electronic | |
dc.format.extent | 4625 - 4636 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER CHEMICAL SOC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Adenosine | |
dc.subject | Crystallography, X-Ray | |
dc.subject | Molecular Conformation | |
dc.subject | Structure-Activity Relationship | |
dc.subject | Dose-Response Relationship, Drug | |
dc.subject | Models, Molecular | |
dc.subject | HSP70 Heat-Shock Proteins | |
dc.title | Exploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of HSP70. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-04-26 | |
rioxxterms.versionofrecord | 10.1021/acs.jmedchem.5b02001 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2016-05-11 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Journal of medicinal chemistry | |
pubs.issue | 10 | |
pubs.notes | Not known | |
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 2 | |
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 2 | |
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 | 59 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Medicinal Chemistry 2 | |
icr.researchteam | Medicinal Chemistry 3 | |
icr.researchteam | Hit Discovery & Structural Design | |
dc.contributor.icrauthor | Cheeseman, Matthew | |
dc.contributor.icrauthor | Burke, Rosemary | |
dc.contributor.icrauthor | Workman, Paul | |
dc.contributor.icrauthor | Collins, Ian | |
dc.contributor.icrauthor | Van Montfort, Robert | |
dc.contributor.icrauthor | Jones, Keith | |