Advances on Keap1-Nrf2 protein-protein interaction inhibitors and degraders
10.16438/j.0513-4870.2022-0669
- VernacularTitle:Keap1-Nrf2蛋白相互作用小分子抑制剂及降解剂研究进展
- Author:
Jian-yu YAN
;
Guo-dong LIU
;
Zhen-yuan MIAO
;
Chun-lin ZHUANG
- Publication Type:Research Article
- Keywords:
oxidative stress;
nuclear factor E2-related factor 2;
Kelch like ECH-associated protein 1;
protein-protein interaction;
proteolysis targeting chimeras
- From:
Acta Pharmaceutica Sinica
2022;57(10):2932-2948
- CountryChina
- Language:Chinese
-
Abstract:
Oxidative stress is a redox imbalance in the body, which is one of the important factors leading to tissue damage and diseases. The nuclear factor E2-related factor 2 (Nrf2)-Kelch like ECH-associated protein 1 (Keap1) signaling pathway is not only an important defense system against oxidative damage, but also one of the key signaling pathways of the antioxidant capacity. Numerous studies have shown that targeting the Keap1-Nrf2 signaling pathway to activate Nrf2 has become an effective strategy for the treatment of oxidative stress and related diseases. Using small molecules to directly block the Keap1-Nrf2 protein-protein interaction (PPI) is one of the important directions for activating Nrf2 and exerting the cytoprotective effect, which can avoid the potential side effects of covalent modification of Nrf2. On the other hand, the Keap1 is an efficient E3 ubiquitin ligase that has been used in the design of proteolysis targeting chimeras (PROTACs). This review summarizes the research progresses of Keap1-Nrf2 protein interaction inhibitors and degraders based on the Keap1 E3 ubiquitination system in recent years.
