There are no files associated with this item.
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.citation.startPage | 103901 | - |
dc.citation.title | BIOORGANIC CHEMISTRY | - |
dc.citation.volume | 101 | - |
dc.contributor.author | Kim, Darong | - |
dc.contributor.author | Kim, So-Yeon | - |
dc.contributor.author | Kim, Dongyoung | - |
dc.contributor.author | Yoon, Nam Gu | - |
dc.contributor.author | Yun, Jisu | - |
dc.contributor.author | Hong, Ki Bum | - |
dc.contributor.author | Lee, Changwook | - |
dc.contributor.author | Lee, Ji Hoon | - |
dc.contributor.author | Kang, Byoung Heon | - |
dc.contributor.author | Kang, Soosung | - |
dc.date.accessioned | 2023-12-21T17:10:17Z | - |
dc.date.available | 2023-12-21T17:10:17Z | - |
dc.date.created | 2020-08-20 | - |
dc.date.issued | 2020-08 | - |
dc.description.abstract | TNF Receptor Associated Protein 1 (TRAP1) is a mitochondrial paralog of Hsp90 related to the promotion of tumorigenesis in various cancers via maintaining mitochondrial integrity, reducing the production of reactive oxygen species, and reprogramming cellular metabolism. Consequently, Hsp90 and TRAP1 have been targeted to develop cancer therapeutics. Herein, we report a series of pyrazolo[3,4-d]pyrimidine derivatives that are mi-tochondria-permeable TRAP1 inhibitors. Structure-based drug design guided the optimization of potency, leading to the identification of compounds 47 and 48 as potent TRAP1 and Hsp90 inhibitors with good meta-bolic and plasma stability as well as acceptable CYP and hERG inhibition. X-ray co-crystallization studies con-firmed both 47 and 48 interact with the ATP binding pocket in the TRAP1 protein. Compounds 47 and 48 demonstrated excellent anticancer efficiency in various cancer cells, with limited toxicity over normal hepato-cyte and prostate cells. Mouse PC3 xenograft studies showed 47 and 48 significantly reduced tumor growth. | - |
dc.identifier.bibliographicCitation | BIOORGANIC CHEMISTRY, v.101, pp.103901 | - |
dc.identifier.doi | 10.1016/j.bioorg.2020.103901 | - |
dc.identifier.issn | 0045-2068 | - |
dc.identifier.scopusid | 2-s2.0-85086711490 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/47850 | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S0045206820300572?via%3Dihub | - |
dc.identifier.wosid | 000552636200003 | - |
dc.language | 영어 | - |
dc.publisher | ACADEMIC PRESS INC ELSEVIER SCIENCE | - |
dc.title | Development of pyrazolo[3,4-d]pyrimidine-6-amine-based TRAP1 inhibitors that demonstrate in vivo anticancer activity in mouse xenograft models | - |
dc.type | Article | - |
dc.description.isOpenAccess | FALSE | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology; Chemistry, Organic | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology; Chemistry | - |
dc.type.docType | Article | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordAuthor | TRAP1 | - |
dc.subject.keywordAuthor | Selectivity | - |
dc.subject.keywordAuthor | Mitochondria | - |
dc.subject.keywordAuthor | Hsp90 | - |
dc.subject.keywordAuthor | Anticancer | - |
dc.subject.keywordAuthor | Drug | - |
dc.subject.keywordPlus | MITOCHONDRIA | - |
dc.subject.keywordPlus | HSP90 | - |
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.