There are no files associated with this item.
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.citation.endPage | 2940 | - |
dc.citation.number | 6 | - |
dc.citation.startPage | 2930 | - |
dc.citation.title | JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.citation.volume | 63 | - |
dc.contributor.author | Hu, Sung | - |
dc.contributor.author | Ferraro, Mariarosaria | - |
dc.contributor.author | Thomas, Ajesh P. | - |
dc.contributor.author | Chung, Jeong Min | - |
dc.contributor.author | Yoon, Nam Gu | - |
dc.contributor.author | Seol, Ji-Hoon | - |
dc.contributor.author | Kim, Sangpil | - |
dc.contributor.author | Kim, Han-Ul | - |
dc.contributor.author | An, Mi Young | - |
dc.contributor.author | Ok, Haewon | - |
dc.contributor.author | Jung, Hyun Suk | - |
dc.contributor.author | Ryu, Ja-Hyoung | - |
dc.contributor.author | Colombo, Giorgio | - |
dc.contributor.author | Kang, Byoung Heon | - |
dc.date.accessioned | 2023-12-21T17:47:14Z | - |
dc.date.available | 2023-12-21T17:47:14Z | - |
dc.date.created | 2020-05-06 | - |
dc.date.issued | 2020-03 | - |
dc.description.abstract | The molecular chaperone TRAP1 is the mitochondrial paralog of Hsp90 and is overexpressed in many cancer cells. The orthosteric ATP-binding site of TRAP1 has been considered the primary inhibitor binding location, but TRAP1 allosteric modulators have not yet been investigated. Here, we generated and characterized the Hsp90 inhibitor PU-H71, conjugated to the mitochondrial delivery vehicle triphenylphosphonium (TPP) with a C-10 carbon spacer, named SMTIN-C10, to enable dual binding to orthosteric and allosteric sites. In addition to tight binding with the ATP-binding site through the PU-H71 moiety, SMTIN-C10 interacts with the E115 residue in the N-terminal domain through the TPP moiety and subsequently induces structural transition of TRAP1 to a tightly packed closed form. The data indicate the existence of a druggable allosteric site neighboring the orthosteric ATP pocket that can be exploited to develop potent TRAP1 modulators. | - |
dc.identifier.bibliographicCitation | JOURNAL OF MEDICINAL CHEMISTRY, v.63, no.6, pp.2930 - 2940 | - |
dc.identifier.doi | 10.1021/acs.jmedchem.9b01420 | - |
dc.identifier.issn | 0022-2623 | - |
dc.identifier.scopusid | 2-s2.0-85082542231 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/32030 | - |
dc.identifier.url | https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b01420 | - |
dc.identifier.wosid | 000526404600013 | - |
dc.language | 영어 | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.title | Dual Binding to Orthosteric and Allosteric Sites Enhances the Anticancer Activity of a TRAP1-Targeting Drug | - |
dc.type | Article | - |
dc.description.isOpenAccess | FALSE | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Medicinal | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.type.docType | Article | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordPlus | PYRUVATE-DEHYDROGENASE KINASE | - |
dc.subject.keywordPlus | HSP90 INHIBITOR | - |
dc.subject.keywordPlus | ATP HYDROLYSIS | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | TRAP1 | - |
dc.subject.keywordPlus | DISCOVERY | - |
dc.subject.keywordPlus | OPTIMIZATION | - |
dc.subject.keywordPlus | SPECIFICITY | - |
dc.subject.keywordPlus | MECHANISM | - |
Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Tel : 052-217-1404 / Email : scholarworks@unist.ac.kr
Copyright (c) 2023 by UNIST LIBRARY. All rights reserved.
ScholarWorks@UNIST was established as an OAK Project for the National Library of Korea.