Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line, Tumor
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Click Chemistry
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Computer Simulation
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Databases, Chemical
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Dose-Response Relationship, Drug
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Fluorescence Polarization
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HEK293 Cells
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Heme Oxygenase-1 / biosynthesis*
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Heme Oxygenase-1 / genetics
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Humans
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Intracellular Signaling Peptides and Proteins / chemistry
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Intracellular Signaling Peptides and Proteins / metabolism*
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Isothiocyanates / chemistry
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Isothiocyanates / pharmacology
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Kelch-Like ECH-Associated Protein 1
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Molecular Docking Simulation
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NAD(P)H Dehydrogenase (Quinone) / biosynthesis*
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NAD(P)H Dehydrogenase (Quinone) / genetics
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NF-E2-Related Factor 2 / chemistry
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NF-E2-Related Factor 2 / metabolism*
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Protein Binding
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Structure-Activity Relationship
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Sulfoxides
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Triazoles / chemical synthesis
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Triazoles / chemistry*
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Triazoles / pharmacology
Substances
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Intracellular Signaling Peptides and Proteins
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Isothiocyanates
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KEAP1 protein, human
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Kelch-Like ECH-Associated Protein 1
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NF-E2-Related Factor 2
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NFE2L2 protein, human
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Sulfoxides
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Triazoles
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HMOX1 protein, human
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Heme Oxygenase-1
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NAD(P)H Dehydrogenase (Quinone)
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NQO1 protein, human
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sulforaphane