J Med Chem. 2023 Sep 14;66(17):11632-11655. doi: 10.1021/acs.jmedchem.3c00770. Epub 2023 Aug 31.
NADPH oxidases (NOXs) form a family of electron-transporting membrane enzymes whose main function is reactive oxygen species (ROS) generation. Strong evidence suggests that ROS produced by NOX enzymes are major contributors to oxidative damage under pathologic conditions. Therefore, blocking the undesirable actions of these enzymes is a therapeutic strategy for treating various pathological disorders, such as cardiovascular diseases, inflammation, and cancer. To date, identification of selective NOX inhibitors is quite challenging, precluding a pharmacologic demonstration of NOX as therapeutic targets . The aim of this Perspective is to furnish an updated outlook about the small-molecule NOX inhibitors described over the last two decades. Structures, activities, and / specificity are discussed, as well as the main biological assays used.
NADPH 氧化酶（NOXs）形成了一类电子传递膜酶家族，其主要功能是产生活性氧物种（ROS）。有强有力的证据表明，NOX 酶产生的 ROS 是病理条件下氧化损伤的主要贡献者。因此，阻断这些酶的不良作用是治疗各种病理疾病的一种治疗策略，如心血管疾病、炎症和癌症。迄今为止，鉴定选择性 NOX 抑制剂极具挑战性，这使得无法通过药理学方法证明 NOX 作为治疗靶点的合理性。本文的目的是提供过去二十年中描述的小分子 NOX 抑制剂的最新观点。讨论了结构、活性和/特异性，以及所使用的主要生物学测定方法。
