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Geldanamycin, a Naturally Occurring Inhibitor of Hsp90 and a Lead Compound for Medicinal Chemistry

dc.contributor.authorKitson, Russell R. A.
dc.contributor.authorKitsonová, Dominika
dc.contributor.authorSiegel, David
dc.contributor.authorRoss, David
dc.contributor.authorMoody, Christopher J.
dc.date.accessioned2024-11-28T12:10:51Z
dc.date.available2024-11-28T12:10:51Z
dc.date.issued2024
dc.identifier.urihttps://hdl.handle.net/20.500.14178/2721
dc.description.abstractGeldanamycin 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.isoen
dc.relation.urlhttp://pubs.acs.org/doi/10.1021/acs.jmedchem.4c01048
dc.rightsCreative Commons Uveďte původ 4.0 Internationalcs
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.titleGeldanamycin, a Naturally Occurring Inhibitor of Hsp90 and a Lead Compound for Medicinal Chemistryen
dcterms.accessRightsopenAccess
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/legalcode
dc.date.updated2024-11-28T12:10:51Z
dc.subject.keywordHsp90en
dc.subject.keywordGeldanamycinen
dc.subject.keywordCanceren
dc.subject.keywordParkinson'sen
dc.subject.keywordMolecular Chaperonesen
dc.identifier.eissn1520-4804
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/MSM//CZ.02.01.01/00/22_008/0004607
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/UK/COOP/COOP
dc.date.embargoStartDate2024-11-28
dc.type.obd73
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1021/acs.jmedchem.4c01048
dc.identifier.utWos001328673900001
dc.identifier.eidScopus2-s2.0-85206186856
dc.identifier.obd655480
dc.identifier.pubmed39361055
dc.subject.rivPrimary30000::30100
dc.subject.rivSecondary10000::10400::10401
dcterms.isPartOf.nameJournal of Medicinal Chemistry
dcterms.isPartOf.issn0022-2623
dcterms.isPartOf.journalYear2024
dcterms.isPartOf.journalVolume67
dcterms.isPartOf.journalIssue20
uk.faculty.primaryId113
uk.faculty.primaryNameFarmaceutická fakulta v Hradci Královécs
uk.faculty.primaryNameFaculty of Pharmacy in Hradec Kraloveen
uk.department.primaryId366
uk.department.primaryNameKatedra organické a bioorganické chemiecs
uk.department.primaryNameDepartment of Organic and Bioorganic Chemistryen
dc.description.pageRange17946-17963
dc.type.obdHierarchyCsČLÁNEK V ČASOPISU::článek v časopisu::přehledový článekcs
dc.type.obdHierarchyEnJOURNAL ARTICLE::journal article::summarizing articleen
dc.type.obdHierarchyCode73::152::205en
uk.displayTitleGeldanamycin, a Naturally Occurring Inhibitor of Hsp90 and a Lead Compound for Medicinal Chemistryen


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