Discipline of Surgery, Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA 5005, Australia.
Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA 5011, Australia.
Molecules. 2023 Apr 21;28(8):3624. doi: 10.3390/molecules28083624.
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.
癌症代谢可塑性，包括脂肪酸代谢利用的变化，现在被广泛认为是癌细胞生长、存活和恶性转化的关键驱动因素。因此，癌症代谢途径一直是最近药物开发的重点。哌克昔林是一种已知通过抑制肉毒碱棕榈酰转移酶 1（CPT1）和 2（CPT2）起作用的预防性抗心绞痛药物，这两种酶是脂肪酸代谢的关键线粒体酶。在这篇综述中，我们讨论了越来越多的证据表明，哌克昔林作为单一疗法或与传统化疗药物联合使用时具有很强的抗癌特性。我们回顾了其抗癌活性的 CPT1/2 依赖性和非依赖性机制。最后，我们推测将哌克昔林重新用作抗癌药物的临床可行性和实用性，包括已知的副作用及其限制其他化疗药物引起的心脏毒性的潜在益处。
