Center for Nanomedicine and Theranostics, Department of Chemistry, Technical University of Denmark, Kemitorvet 207, 2800 Kgs. Lyngby, Denmark.
J Med Chem. 2021 May 13;64(9):5252-5275. doi: 10.1021/acs.jmedchem.0c01914. Epub 2021 Apr 15.
Reactive oxygen species (ROS) are involved in physiological cellular processes including differentiation, proliferation, and apoptosis by acting as signaling molecules or regulators of transcription factors. The maintenance of appropriate cellular ROS levels is termed redox homeostasis, a balance between their production and neutralization. High concentrations of ROS may contribute to severe pathological events including cancer, neurodegenerative, and cardiovascular diseases. In recent years, approaches to target the sources of ROS production directly in order to develop tool compounds or potential therapeutics have been explored. Herein, we briefly outline the major sources of cellular ROS production and comprehensively review the targeting of these by small-molecule inhibitors. We critically assess the value of ROS inhibitors with different mechanisms-of-action, including their potency, mode-of-action, known off-target effects, and clinical or preclinical status, while suggesting future avenues of research in the field.
活性氧（ROS）作为信号分子或转录因子的调节剂，参与细胞分化、增殖和凋亡等生理过程。通过其产生和中和之间的平衡来维持适当的细胞 ROS 水平，这被称为氧化还原稳态。ROS 的高浓度可能会导致严重的病理事件，包括癌症、神经退行性和心血管疾病。近年来，人们探索了直接针对 ROS 产生源的方法，以开发工具化合物或潜在的治疗药物。在此，我们简要概述了细胞内 ROS 产生的主要来源，并全面综述了小分子抑制剂对这些来源的靶向作用。我们批判性地评估了具有不同作用机制的 ROS 抑制剂的价值，包括其效力、作用模式、已知的脱靶效应以及临床或临床前状态，同时为该领域的未来研究提出了建议。
