Design, synthesis, and evaluation of triazole derivatives that induce Nrf2 dependent gene products and inhibit the Keap1-Nrf2 protein-protein interaction

Hélène C. Bertrand, Marjolein Schaap, Liam Baird, Nikolaos D. Georgakopoulos, Adrian Fowkes, Clarisse Thiollier, Hiroko Kachi, Albena T. Dinkova-Kostova, Geoff Wells (Lead / Corresponding author)

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    57 Citations (Scopus)


    The transcription factor Nrf2 regulates the expression of a large network of cytoprotective and metabolic enzymes and proteins. Compounds that directly and reversibly inhibit the interaction between Nrf2 and its main negative regulator Keap1 are potential pharmacological agents for a range of disease types including neurodegenerative conditions and cancer. We describe the development of a series of 1,4-diphenyl-1,2,3-triazole compounds that inhibit the Nrf2-Keap1 protein-protein interaction (PPI) in vitro and in live cells and up-regulate the expression of Nrf2-dependent gene products.

    Original languageEnglish
    Pages (from-to)7186-7194
    Number of pages9
    JournalJournal of Medicinal Chemistry
    Issue number18
    Publication statusPublished - 24 Sep 2015



    • Cell Line, Tumor
    • Click chemistry
    • Computer simulation
    • Databases, Chemical
    • Dose-response relationship, Drug
    • Fluorescence polarization
    • HEK293 cells
    • Heme oxygenase-1
    • Humans
    • Intracellular signaling Peptides and Proteins
    • Isothiocyanates
    • Molecular docking simulation
    • NAD(P)H dehydrogenase (Quinone)
    • NF-E2-related factor 2
    • Protein binding
    • Structure-activity relationship
    • Triazoles

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