Bis-Michael Acceptors as Novel Probes to Study the Keap1/Nrf2/ARE Pathway

Nuclear
factor erythroid 2-related factor 2 (Nrf2) is a master
regulator that promotes the transcription of cytoprotective genes
in response to oxidative/electrophilic stress. Various Michael-type
compounds were designed and synthesized, and their potency to activate
the Keap1/Nrf2/ARE pathway was evaluated. Compounds bearing two Michael-type
acceptors proved to be the most active. Tether length and rigidity
between the acceptors was crucial. This study will help to understand
how this feature disrupts the interaction between Keap1 and Nrf2.