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Bis-Michael Acceptors as Novel Probes to Study the Keap1/Nrf2/ARE Pathway
Ludovic J Deny1,2, Hussein Traboulsi2,3, André M Cantin2,3
1Département de Chimie, Université de Sherbrooke , 2500 Boulevard Université, Sherbrooke, Québec J1K 2R1, Canada.
Abstract:
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.

