dc.contributor.author | Antolin, AA | |
dc.contributor.author | Clarke, PA | |
dc.contributor.author | Collins, I | |
dc.contributor.author | Workman, P | |
dc.contributor.author | Al-Lazikani, B | |
dc.date.accessioned | 2021-08-12T09:11:00Z | |
dc.date.available | 2021-08-12T09:11:00Z | |
dc.date.issued | 2021-10-21 | |
dc.identifier.citation | Cell chemical biology, 2021 | |
dc.identifier.issn | 2451-9456 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4745 | |
dc.identifier.eissn | 2451-9448 | |
dc.identifier.doi | 10.1016/j.chembiol.2021.05.004 | |
dc.description.abstract | Most small molecules interact with several target proteins but this polypharmacology is seldom comprehensively investigated or explicitly exploited during drug discovery. Here, we use computational and experimental methods to identify and systematically characterize the kinase cross-pharmacology of representative HSP90 inhibitors. We demonstrate that the resorcinol clinical candidates ganetespib and, to a lesser extent, luminespib, display unique off-target kinase pharmacology as compared with other HSP90 inhibitors. We also demonstrate that polypharmacology evolved during the optimization to discover luminespib and that the hit, leads, and clinical candidate all have different polypharmacological profiles. We therefore recommend the computational and experimental characterization of polypharmacology earlier in drug discovery projects to unlock new multi-target drug design opportunities. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Evolution of kinase polypharmacology across HSP90 drug discovery. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-05-05 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.chembiol.2021.05.004 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2021-05-27 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cell chemical biology | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/ImmNet | |
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/Computational Biology and Chemogenomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 2 | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/ImmNet | |
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/Computational Biology and Chemogenomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 2 | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology | |
pubs.publication-status | Published | |
pubs.embargo.terms | Not known | |
icr.researchteam | Computational Biology and Chemogenomics | |
icr.researchteam | Medicinal Chemistry 2 | |
icr.researchteam | Signal Transduction & Molecular Pharmacology | |
icr.researchteam | Computational Biology and Chemogenomics | |
icr.researchteam | Medicinal Chemistry 2 | |
icr.researchteam | Signal Transduction & Molecular Pharmacology | |
dc.contributor.icrauthor | Clarke, Paul | |
dc.contributor.icrauthor | Collins, Ian | |
dc.contributor.icrauthor | Workman, Paul | |
dc.contributor.icrauthor | Al-Lazikani, Bissan | |