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.
Département de Chimie, Université de Sherbrooke , 2500 Boulevard Université, Sherbrooke, Québec J1K 2R1, Canada.|Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke , Sherbrooke, Québec J1H 5N4, Canada.
Ludovic J
LJ
Deny
Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke , Sherbrooke, Québec J1H 5N4, Canada.|Département de Médecine, Service de Pneumologie et Centre de Recherche Clinique, Centre Hospitalier de l'Université de Sherbrooke , Sherbrooke, Québec J1H 5N4, Canada.
Hussein
H
Traboulsi
Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke , Sherbrooke, Québec J1H 5N4, Canada.|Département de Médecine, Service de Pneumologie et Centre de Recherche Clinique, Centre Hospitalier de l'Université de Sherbrooke , Sherbrooke, Québec J1H 5N4, Canada.
André M
AM
Cantin
Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke , Sherbrooke, Québec J1H 5N4, Canada.|Département de Pharmacologie, Université de Sherbrooke , Sherbrooke, Québec J1K 2R1, Canada.
Éric
É
Marsault
Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke , Sherbrooke, Québec J1H 5N4, Canada.|Département de Médecine, Service de Pneumologie et Centre de Recherche Clinique, Centre Hospitalier de l'Université de Sherbrooke , Sherbrooke, Québec J1H 5N4, Canada.
Martin V
MV
Richter
Département de Chimie, Université de Sherbrooke , 2500 Boulevard Université, Sherbrooke, Québec J1K 2R1, Canada.|Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke , Sherbrooke, Québec J1H 5N4, Canada.
Guillaume
G
Bélanger
D000818:Animals; D061745:Antioxidant Response Elements; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D000072019:Kelch-Like ECH-Associated Protein 1 / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000975:Antioxidants; C431364:KEAP1 protein, human; C117301:Keap1 protein, mouse; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2