Sova Matej, Saso Luciano
Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia,
Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University, Rome, Italy.
Drug Des Devel Ther. 2018 Sep 25;12:3181-3197. doi: 10.2147/DDDT.S172612. eCollection 2018.
A major cell defense mechanism against oxidative and xenobiotic stress is mediated by the Nrf2/Keap1 signaling pathway. The Nrf2/Keap1 pathway regulates gene expression of many cytoprotective and detoxifying enzymes, thus playing a pivotal role in maintaining redox cellular homeostasis. Many diseases including cancer have been closely related to impaired Nrf2 activity. Targeting Nrf2 and modulating its activity represents a novel modern strategy for cancer chemoprevention and therapy. In this review, different design strategies used for the development of Nrf2 modulators are described in detail. Moreover, the main focus is on important and recently developed Nrf2 activators and inhibitors, their in vitro and in vivo studies, and their potential use as chemopreventive agents and/or cancer therapeutics.
细胞对抗氧化和外源性应激的主要防御机制由Nrf2/Keap1信号通路介导。Nrf2/Keap1通路调节许多细胞保护和解毒酶的基因表达，从而在维持细胞氧化还原稳态中发挥关键作用。包括癌症在内的许多疾病都与Nrf2活性受损密切相关。靶向Nrf2并调节其活性是癌症化学预防和治疗的一种新型现代策略。在这篇综述中，详细描述了用于开发Nrf2调节剂的不同设计策略。此外，主要关注的是重要且最近开发的Nrf2激活剂和抑制剂、它们的体外和体内研究，以及它们作为化学预防剂和/或癌症治疗药物的潜在用途。
