Non-electrophilic modulators of the canonical Keap1/Nrf2 pathway.
Nrf2 is the major transcription factor that regulates many of the cytoprotective enzymes involved in the adaptive stress response. Modulation of Nrf2 could be therapeutically useful in a number of disease states. Activation can occur through either an electrophilic or non-electrophilic mechanism. To date, most of the research has focused on electrophilic Nrf2 activators, but there is increasing interest in non-electrophilic modulators of Nrf2. This Digest examines the current selection of small molecules that modulate Nrf2 through non-electrophilic mechanisms, and it highlights new opportunities for this important therapeutic target.
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, 833 S. Wood St., Chicago, IL 60612, United States.
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Richardson
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, 833 S. Wood St., Chicago, IL 60612, United States.
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Jain
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, 833 S. Wood St., Chicago, IL 60612, United States.
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Speltz
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, 833 S. Wood St., Chicago, IL 60612, United States; University of Illinois Cancer Center, University of Illinois at Chicago, 833 S. Wood St., Chicago, IL 60612, United States. Electronic address: twmoore@uic.edu.
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Moore
D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000072019:Kelch-Like ECH-Associated Protein 1; D008958:Models, Molecular; D051267:NF-E2-Related Factor 2 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D015398:Signal Transduction / Q000187:drug effects*
D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2
Adaptive stress response; Cul3; Keap1; Nrf2; Nrf2 activator; Nrf2 repressor; Nrf2/Keap1 interaction; Protein–protein interaction