Andrew Gutierrez, Jason Archdeacon, Brian S.J. Blagg
{"title":"TRAP1 and its therapeutic potential","authors":"Andrew Gutierrez, Jason Archdeacon, Brian S.J. Blagg","doi":"10.1016/j.bmcl.2025.130395","DOIUrl":null,"url":null,"abstract":"<div><div>The mitochondrial Hsp90 isoform, Tumor Necrosis Factor Receptor Associated Protein 1 (TRAP1), is central to the pathogenesis of disease states that include cancer, ischemic retinopathy, and diabetic kidney disease among others. TRAP1 contributes to these diseases through the regulation of mitochondrial metabolism, apoptosis, oxidative stress, cell signaling and angiogenesis through interactions with client proteins. Numerous TRAP1-selective inhibitors have been developed to limit the toxicities associated with Hsp90 pan-inhibition, while leveraging the therapeutic benefits of TRAP1 inhibition. This review focuses on these inhibitors and the potential clinical uses of TRAP1-directed therapies.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"129 ","pages":"Article 130395"},"PeriodicalIF":2.2000,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic & Medicinal Chemistry Letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0960894X2500304X","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
The mitochondrial Hsp90 isoform, Tumor Necrosis Factor Receptor Associated Protein 1 (TRAP1), is central to the pathogenesis of disease states that include cancer, ischemic retinopathy, and diabetic kidney disease among others. TRAP1 contributes to these diseases through the regulation of mitochondrial metabolism, apoptosis, oxidative stress, cell signaling and angiogenesis through interactions with client proteins. Numerous TRAP1-selective inhibitors have been developed to limit the toxicities associated with Hsp90 pan-inhibition, while leveraging the therapeutic benefits of TRAP1 inhibition. This review focuses on these inhibitors and the potential clinical uses of TRAP1-directed therapies.
期刊介绍:
Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.