An updated patent review of Nrf2 activators (2020-present)

IntroductionThe nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal transcription factor that controls the expression of numerous cytoprotective genes and regulates cellular defense system against oxidative insults. Thus, activating the Nrf2 pathway is a promising strategy for the treatment of various chronic diseases characterized by oxidative stress.Areas coveredThis review first discusses the biological effects of Nrf2 and the regulatory mechanism of Kelch-like ECH-associated protein 1-Nrf2-antioxidant response element (Keap1-Nrf2-ARE) pathway. Then, Nrf2 activators (2020-present) are summarized based on the mechanism of action. The case studies consist of chemical structures, biological activities, structural optimization, and clinical development.Expert opinionExtensive efforts have been devoted to developing novel Nrf2 activators with improved potency and drug-like properties. These Nrf2 activators have exhibited beneficial effects in in vitro and in vivo models of oxidative stress-related chronic diseases. However, some specific problems, such as target selectivity and brain blood barrier (BBB) permeability, still need to be addressed in the future.

Automated summary

The Nrf2 pathway plays a crucial role in protecting cells against oxidative stress, and activating this pathway has potential therapeutic implications for oxidative stress-related chronic diseases. This review summarizes the biological effects of Nrf2, the regulatory mechanism of the Keap1-Nrf2-ARE pathway, and the development of Nrf2 activators.