The proteins Keap1 and Nrf2 together act as a cytoprotective mechanism that enables cells to overcome electrophilic and oxidative stress. Research has shown that manipulating this system by modulating the Keap1-Nrf2 interaction either through inhibition at the binding interface or via the covalent modification of Keap1 could provide a powerful therapeutic strategy for a range of diseases. However, despite intensive investigation of the system and significant progress in the development of inhibitory small molecules, there is still much to learn about the pathways associated with the Keap1-Nrf2 system and the structural details underpinning its mechanism of action. In this review, we discuss how a deeper understanding could prove revolutionary in the development of new inhibitors and activators as well as guiding how to best harness Keap1 for targeted protein degradation.

中文翻译：

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对Keap1-Nrf2系统的结构和机制洞察力，以此作为药物发现的途径。

蛋白质Keap1和Nrf2共同起细胞保护机制的作用，使细胞能够克服亲电和氧化应激。研究表明，通过抑制Keap1-Nrf2相互作用（通过在结合界面处抑制或通过Keap1的共价修饰）来操纵该系统可以为多种疾病提供强大的治疗策略。然而，尽管对该系统进行了深入的研究并且在抑制性小分子的发展方面取得了重大进展，但是与Keap1-Nrf2系统相关的途径以及构成其作用机理的结构细节仍然有很多东西要学习。在这篇评论中