Cifuentes-Pagano M Eugenia, Meijles Daniel N, Pagano Patrick J
Department of Pharmacology & Chemical Biology, Vascular Medicine Institute, University of Pittsburgh School of Medicine, Biomedical Science Tower, 12th Floor, Room E1247, 200 Lothrop St., Pittsburgh, PA 15261, USA.
Curr Pharm Des. 2015;21(41):6023-35. doi: 10.2174/1381612821666151029112013.
Oxidative stress-related diseases underlie many if not all of the major leading causes of death in United States and the Western World. Thus, enormous interest from both academia and pharmaceutical industry has been placed on the development of agents which attenuate oxidative stress. With that in mind, great efforts have been placed in the development of inhibitors of NADPH oxidase (Nox), the major enzymatic source of reactive oxygen species and oxidative stress in many cells and tissue. The regulation of a catalytically active Nox enzyme involves numerous protein-protein interactions which, in turn, afford numerous targets for inhibition of its activity. In this review, we will provide an updated overview of the available Nox inhibitors, both peptidic and small molecules, and discuss the body of data related to their possible mechanisms of action and specificity towards each of the various isoforms of Nox. Indeed, there have been some very notable successes. However, despite great commitment by many in the field, the need for efficacious and well-characterized, isoform-specific Nox inhibitors, essential for the treatment of major diseases as well as for delineating the contribution of a given Nox in physiological redox signalling, continues to grow.
氧化应激相关疾病是美国和西方世界许多（即便不是所有）主要死因的潜在病因。因此，学术界和制药行业都对开发减轻氧化应激的药物产生了浓厚兴趣。考虑到这一点，人们在开发NADPH氧化酶（Nox）抑制剂方面付出了巨大努力，Nox是许多细胞和组织中活性氧和氧化应激的主要酶源。具有催化活性的Nox酶的调节涉及众多蛋白质-蛋白质相互作用，这反过来又为抑制其活性提供了众多靶点。在这篇综述中，我们将提供有关现有Nox抑制剂（包括肽类和小分子抑制剂）的最新概述，并讨论与其可能的作用机制以及对Nox各种同工型的特异性相关的数据。确实，已经取得了一些非常显著的成功。然而，尽管该领域的许多人付出了巨大努力，但对于治疗重大疾病以及阐明特定Nox在生理氧化还原信号传导中的作用至关重要的有效且特征明确的同工型特异性Nox抑制剂的需求仍在不断增长。
