Liu Shangde, Wang Jian
School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing, 100084, China.
Mini Rev Med Chem. 2025;25(1):42-57. doi: 10.2174/0113895575308546240607073310.
Ferroptosis is a novel type of programmed cell death that relies on the build-up of intracellular iron and leads to an increase in toxic lipid peroxides. Glutathione Peroxidase 4 (GPX4) is a crucial regulator of ferroptosis that uses glutathione as a cofactor to detoxify cellular lipid peroxidation. Targeting GPX4 in cancer could be a promising strategy to induce ferroptosis and kill drugresistant cancers effectively. Currently, research on GPX4 inhibitors is of increasing interest in the field of anti-tumor agents. Many reviews have summarized the regulation and ferroptosis induction of GPX4 in human cancer and disease. However, insufficient attention has been paid to GPX4 inhibitors. This article outlines the molecular structures and development prospects of GPX4 inhibitors as novel anticancer agents.
铁死亡是一种新型的程序性细胞死亡，它依赖于细胞内铁的积累，并导致有毒脂质过氧化物增加。谷胱甘肽过氧化物酶4（GPX4）是铁死亡的关键调节因子，它利用谷胱甘肽作为辅因子来解毒细胞脂质过氧化。在癌症中靶向GPX4可能是诱导铁死亡并有效杀死耐药性癌症的一种有前景的策略。目前，关于GPX4抑制剂的研究在抗肿瘤药物领域越来越受到关注。许多综述总结了GPX4在人类癌症和疾病中的调节及铁死亡诱导作用。然而，对GPX4抑制剂的关注还不够。本文概述了GPX4抑制剂作为新型抗癌药物的分子结构和发展前景。
