dc.contributor.author | Kitson, Russell R. A. | |
dc.contributor.author | Kitsonová, Dominika | |
dc.contributor.author | Siegel, David | |
dc.contributor.author | Ross, David | |
dc.contributor.author | Moody, Christopher J. | |
dc.date.accessioned | 2024-11-28T12:10:51Z | |
dc.date.available | 2024-11-28T12:10:51Z | |
dc.date.issued | 2024 | |
dc.identifier.uri | https://hdl.handle.net/20.500.14178/2721 | |
dc.description.abstract | Geldanamycin remains a driver in the medicinal chemistry of heat shock protein 90 (Hsp90) inhibition, even half a century after its original isolation from nature. This Perspective focuses on the properties of the benzoquinone ring of the natural product that enable a range of functionalization reactions to take place. Therefore, inherent reactivity at C-17, where the methoxy group serves as a vinylogous ester, and at C-19 that demonstrates nucleophilic, enamide-type character toward electrophiles, and also as a conjugate acceptor to react with nucleophiles, has facilitated the synthesis of semisynthetic derivatives. Thus, a range of C-17-substituted amine derivatives has been investigated in oncology applications, with a number of compounds in this series reaching clinical trials. In contrast, the 19-position of geldanamycin has received less attention, although 19-substituted derivatives offer promise with markedly reduced toxicity compared to geldanamycin itself, while retaining Hsp90 inhibitory activity albeit with diminished potency in cellular studies. | en |
dc.language.iso | en | |
dc.relation.url | http://pubs.acs.org/doi/10.1021/acs.jmedchem.4c01048 | |
dc.rights | Creative Commons Uveďte původ 4.0 International | cs |
dc.rights | Creative Commons Attribution 4.0 International | en |
dc.title | Geldanamycin, a Naturally Occurring Inhibitor of Hsp90 and a Lead Compound for Medicinal Chemistry | en |
dcterms.accessRights | openAccess | |
dcterms.license | https://creativecommons.org/licenses/by/4.0/legalcode | |
dc.date.updated | 2024-11-28T12:10:51Z | |
dc.subject.keyword | Hsp90 | en |
dc.subject.keyword | Geldanamycin | en |
dc.subject.keyword | Cancer | en |
dc.subject.keyword | Parkinson's | en |
dc.subject.keyword | Molecular Chaperones | en |
dc.identifier.eissn | 1520-4804 | |
dc.relation.fundingReference | info:eu-repo/grantAgreement/MSM//CZ.02.01.01/00/22_008/0004607 | |
dc.relation.fundingReference | info:eu-repo/grantAgreement/UK/COOP/COOP | |
dc.date.embargoStartDate | 2024-11-28 | |
dc.type.obd | 73 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | |
dc.identifier.doi | 10.1021/acs.jmedchem.4c01048 | |
dc.identifier.utWos | 001328673900001 | |
dc.identifier.eidScopus | 2-s2.0-85206186856 | |
dc.identifier.obd | 655480 | |
dc.identifier.pubmed | 39361055 | |
dc.subject.rivPrimary | 30000::30100 | |
dc.subject.rivSecondary | 10000::10400::10401 | |
dcterms.isPartOf.name | Journal of Medicinal Chemistry | |
dcterms.isPartOf.issn | 0022-2623 | |
dcterms.isPartOf.journalYear | 2024 | |
dcterms.isPartOf.journalVolume | 67 | |
dcterms.isPartOf.journalIssue | 20 | |
uk.faculty.primaryId | 113 | |
uk.faculty.primaryName | Farmaceutická fakulta v Hradci Králové | cs |
uk.faculty.primaryName | Faculty of Pharmacy in Hradec Kralove | en |
uk.department.primaryId | 366 | |
uk.department.primaryName | Katedra organické a bioorganické chemie | cs |
uk.department.primaryName | Department of Organic and Bioorganic Chemistry | en |
dc.description.pageRange | 17946-17963 | |
dc.type.obdHierarchyCs | ČLÁNEK V ČASOPISU::článek v časopisu::přehledový článek | cs |
dc.type.obdHierarchyEn | JOURNAL ARTICLE::journal article::summarizing article | en |
dc.type.obdHierarchyCode | 73::152::205 | en |
uk.displayTitle | Geldanamycin, a Naturally Occurring Inhibitor of Hsp90 and a Lead Compound for Medicinal Chemistry | en |