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

doi:10.1021/acs.jmedchem.5b00602

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

74 Scopus citations

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.

Original language	English (US)
Pages (from-to)	7186-7194
Number of pages	9
Journal	Journal of Medicinal Chemistry
Volume	58
Issue number	18
DOIs	https://doi.org/10.1021/acs.jmedchem.5b00602
State	Published - Sep 24 2015

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery
General Medicine

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Bertrand, H. C., Schaap, M., Baird, L., Georgakopoulos, N. D., Fowkes, A., Thiollier, C., Kachi, H., Dinkova-Kostova, A. T., & Wells, G. (2015). Design, Synthesis, and Evaluation of Triazole Derivatives That Induce Nrf2 Dependent Gene Products and Inhibit the Keap1-Nrf2 Protein-Protein Interaction. Journal of Medicinal Chemistry, 58(18), 7186-7194. https://doi.org/10.1021/acs.jmedchem.5b00602

Bertrand, HC, Schaap, M, Baird, L, Georgakopoulos, ND, Fowkes, A, Thiollier, C, Kachi, H, Dinkova-Kostova, AT & Wells, G 2015, 'Design, Synthesis, and Evaluation of Triazole Derivatives That Induce Nrf2 Dependent Gene Products and Inhibit the Keap1-Nrf2 Protein-Protein Interaction', Journal of Medicinal Chemistry, vol. 58, no. 18, pp. 7186-7194. https://doi.org/10.1021/acs.jmedchem.5b00602

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AU - Schaap, Marjolein

AU - Baird, Liam

AU - Georgakopoulos, Nikolaos D.

AU - Fowkes, Adrian

AU - Thiollier, Clarisse

AU - Kachi, Hiroko

AU - Dinkova-Kostova, Albena T.

AU - Wells, Geoff

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Design, Synthesis, and Evaluation of Triazole Derivatives That Induce Nrf2 Dependent Gene Products and Inhibit the Keap1-Nrf2 Protein-Protein Interaction

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