Recent progress in Keap1-Nrf2 protein-protein interaction inhibitors

Therapeutic targeting the protein-protein interaction (PPI) of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its main regulator, Kelch-like ECH-Associating protein 1 (Keap1) has been emerged as a feasible way to combat oxidative stress related diseases, due to the key role of Nrf2 in oxidative stress regulation. In recent years, many efforts have been made to develop potent Keap1-Nrf2 inhibitors with new chemical structures. Various molecules with diverse chemical structures have been reported and some compounds exhibit high potency. This review summarizes peptide and small molecule Keap1-Nrf2 inhibitors reported recently. We also highlight the pharmacological effects and discuss the possible therapeutic application of Keap1-Nrf2 inhibitors. [Display omitted] •Enhancing Nrf2 activity via disrupting Keap1-Nrf2 interaction is a furnish way for drug development.•Various potent Keap1-Nrf2 inhibitors have been reported and some molecules showed proper drug-like properties.•Keap1-Nrf2 inhibitors have shown the expected efficacy in several in vivo models.•Keap1 related interactome and the oncogenic role of Nrf2 are new concerns for further development .