Nrf2 activation through the inhibition of Keap1–Nrf2 protein–protein interaction

被引：0
作者：
Sumi Lee
Longqin Hu
机构：
[1] The State University of New Jersey,Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers
[2] Cancer Institute of New Jersey,undefined
来源：
Medicinal Chemistry Research | 2020年 / 29卷
关键词：
Keap1; Nrf2; Keap1–Nrf2 interaction; Protein–protein interaction Inhibitor; Oxidative stress; Structure–activity relationship;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Activation of the transcription factor Nrf2 via the Keap1–Nrf2–ARE signaling system regulates the transcription and subsequent expression of cellular cytoprotective proteins and plays a crucial role in preventing pathological conditions exacerbated by the overproduction of oxidative stress. In addition to electrophilic modulators, direct noncovalent inhibitors that interrupt the Keap1–Nrf2 protein–protein interaction (PPI) leading to Nrf2 activation have attracted a great deal of attention as potential preventive and therapeutic agents for oxidative stress-related diseases. Structural studies of Keap1-binding ligands, development of biochemical and cellular assays, and new structure-based design approaches have facilitated the discovery of small molecule PPI inhibitors. This perspective reviews the Keap1–Nrf2–ARE system, its physiological functions, and the recent progress in the discovery and the potential applications of direct inhibitors of Keap1–Nrf2 PPI.
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页码：846 / 867
页数：21
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