{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:18:12Z","timestamp":1791616692438,"version":"4.3.4"},"reference-count":100,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Hospital Research Foundation (THRF)\/Cancer Council SA Beat Cancer Hospital Research Package"},{"name":"Schlumberger Foundation Faculty for Future Fellowship"},{"name":"THRF Early Career Fellowship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cancer metabolic plasticity, including changes in fatty acid metabolism utilisation, is now widely appreciated as a key driver for cancer cell growth, survival and malignancy. Hence, cancer metabolic pathways have been the focus of much recent drug development. Perhexiline is a prophylactic antianginal drug known to act by inhibiting carnitine palmitoyltransferase 1 (CPT1) and 2 (CPT2), mitochondrial enzymes critical for fatty acid metabolism. In this review, we discuss the growing evidence that perhexiline has potent anti-cancer properties when tested as a monotherapy or in combination with traditional chemotherapeutics. We review the CPT1\/2 dependent and independent mechanisms of its anti-cancer activities. Finally, we speculate on the clinical feasibility and utility of repurposing perhexiline as an anti-cancer agent, its limitations including known side effects and its potential added benefit of limiting cardiotoxicity induced by other chemotherapeutics.<\/jats:p>","DOI":"10.3390\/molecules28083624","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T04:48:11Z","timestamp":1682052491000},"page":"3624","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Perhexiline: Old Drug, New Tricks? A Summary of Its Anti-Cancer Effects"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2658-6380","authenticated-orcid":false,"given":"Bimala","family":"Dhakal","sequence":"first","affiliation":[{"name":"Discipline of Surgery, Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA 5011, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7934-2203","authenticated-orcid":false,"given":"Yoko","family":"Tomita","sequence":"additional","affiliation":[{"name":"Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA 5011, Australia"},{"name":"Medical Oncology, The Queen Elizabeth Hospital, Adelaide, SA 5011, Australia"},{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Drew","sequence":"additional","affiliation":[{"name":"Discipline of Surgery, Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA 5011, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Price","sequence":"additional","affiliation":[{"name":"Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA 5011, Australia"},{"name":"Medical Oncology, The Queen Elizabeth Hospital, Adelaide, SA 5011, Australia"},{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Maddern","sequence":"additional","affiliation":[{"name":"Discipline of Surgery, Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA 5011, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2958-3492","authenticated-orcid":false,"given":"Eric","family":"Smith","sequence":"additional","affiliation":[{"name":"Discipline of Surgery, Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA 5011, Australia"},{"name":"Medical Oncology, The Queen Elizabeth Hospital, Adelaide, SA 5011, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1619-1406","authenticated-orcid":false,"given":"Kevin","family":"Fenix","sequence":"additional","affiliation":[{"name":"Discipline of Surgery, Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA 5011, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/nrc.2016.89","article-title":"The multifaceted roles of fatty acid synthesis in cancer","volume":"16","author":"Rohrig","year":"2016","journal-title":"Nat. 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