NRF2 is a basic leucine zipper (bZip) transcription factor that is the master regulator of redox homeostasis. Under basal conditions, the cellular level of NRF2 is low due to a posttranslational regulation by the ubiquitin proteasome system (UPS). But, when an organism is challenged with oxidative or xenobiotic stress, the NRF2 pathway is activated by inhibition of the E3 ubiquitin ligase complex that normally marks NRF2 for destruction. For several decades, researchers have searched for molecules that can intentionally activate NRF2, as this was shown to be a means to prevent certain diseases, at least in animal models. In the present era, there are many compounds known to activate the NRF2 pathway including natural products and synthetic compounds, covalent and non-covalent compounds, and others. However, it was also revealed that like many protective pathways, the NRF2 pathway has a dark side. Just as NRF2 can protect normal cells from damage, it can protect malignant cells from damage. As cells transform, they are exposed to many stressors and aberrant upregulation of NRF2 can facilitate transformation and it can help cancer cells to grow, to spread, and to resist treatment. For this reason, researchers are also interested in the discovery and development of NRF2 inhibitors. In the present review, we will begin with a general discussion of NRF2 structure and function, we will discuss the latest in NRF2 non-covalent activators, and we will discuss the current state of NRF2 inhibitors.

NRF2 是一种基本的亮氨酸拉链 (bZip) 转录因子，是氧化还原稳态的主要调节因子。在基础条件下，由于泛素蛋白酶体系统 (UPS) 的翻译后调节，NRF2 的细胞水平较低。但是，当生物体受到氧化或外源性应激的挑战时，NRF2 途径会通过抑制通常标记 NRF2 被破坏的 E3 泛素连接酶复合物而被激活。几十年来，研究人员一直在寻找可以有意激活 NRF2 的分子，因为这被证明是预防某些疾病的一种手段，至少在动物模型中是这样。在当今时代，已知有许多化合物可以激活 NRF2 途径，包括天然产物和合成化合物、共价和非共价化合物等。然而，还发现，与许多保护途径一样，NRF2 途径也有阴暗面。正如 NRF2 可以保护正常细胞免受损害一样，它也可以保护恶性细胞免受损害。当细胞转化时，它们会暴露在许多压力源中，NRF2 的异常上调可以促进转化，它可以帮助癌细胞生长、扩散和抵抗治疗。出于这个原因，研究人员也对 NRF2 抑制剂的发现和开发感兴趣。在本综述中，我们将从对 NRF2 结构和功能的一般性讨论开始，我们将讨论 NRF2 非共价激活剂的最新进展，并讨论 NRF2 抑制剂的现状。它们暴露于许多压力源中，NRF2 的异常上调可以促进转化，它可以帮助癌细胞生长、扩散和抵抗治疗。出于这个原因，研究人员也对 NRF2 抑制剂的发现和开发感兴趣。在本综述中，我们将从对 NRF2 结构和功能的一般性讨论开始，我们将讨论 NRF2 非共价激活剂的最新进展，并讨论 NRF2 抑制剂的现状。它们暴露于许多压力源中，NRF2 的异常上调可以促进转化，它可以帮助癌细胞生长、扩散和抵抗治疗。出于这个原因，研究人员也对 NRF2 抑制剂的发现和开发感兴趣。在本综述中，我们将从对 NRF2 结构和功能的一般性讨论开始，我们将讨论 NRF2 非共价激活剂的最新进展，并讨论 NRF2 抑制剂的现状。