College of Pharmacy and Chemistry & Chemical Engineering, Taizhou University, Taizhou, 225300, China.
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China.
Eur J Med Chem. 2020 Sep 15;202:112532. doi: 10.1016/j.ejmech.2020.112532. Epub 2020 Jul 6.
Therapeutic targeting the protein-protein interaction (PPI) of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its main regulator, Kelch-like ECH-Associating protein 1 (Keap1) has been emerged as a feasible way to combat oxidative stress related diseases, due to the key role of Nrf2 in oxidative stress regulation. In recent years, many efforts have been made to develop potent Keap1-Nrf2 inhibitors with new chemical structures. Various molecules with diverse chemical structures have been reported and some compounds exhibit high potency. This review summarizes peptide and small molecule Keap1-Nrf2 inhibitors reported recently. We also highlight the pharmacological effects and discuss the possible therapeutic application of Keap1-Nrf2 inhibitors.
治疗性靶向核因子（红细胞衍生 2 样 2）（Nrf2）与其主要调节剂 Kelch 样 ECH 相关蛋白 1（Keap1）的蛋白-蛋白相互作用（PPI）已经成为对抗氧化应激相关疾病的一种可行方法，因为 Nrf2 在氧化应激调节中起关键作用。近年来，人们致力于开发具有新化学结构的强效 Keap1-Nrf2 抑制剂。已经报道了具有不同化学结构的各种分子，其中一些化合物具有很高的活性。本文综述了最近报道的肽和小分子 Keap1-Nrf2 抑制剂。我们还强调了 Keap1-Nrf2 抑制剂的药理学作用，并讨论了其可能的治疗应用。
