Design, Synthesis, and Evaluation of Triazole Derivatives That Induce Nrf2 Dependent Gene Products and Inhibit the Keap1鈥揘rf2 Protein鈥揚rotein Interaction
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- 作者：H茅l猫ne C. Bertrand ; Marjolein Schaap ; Liam Baird ; Nikolaos D. Georgakopoulos ; Adrian Fowkes ; Clarisse Thiollier ; Hiroko Kachi ; Albena T. Dinkova-Kostova ; Geoff Wells
- 刊名：Journal of Medicinal Chemistry
- 出版年：2015
- 出版时间：September 24, 2015
- 年：2015
- 卷：58
- 期：18
- 页码：7186-7194
- 全文大小：495K
- ISSN：1520-4804
文摘
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鈥揔eap1 protein鈥損rotein interaction (PPI) in vitro and in live cells and up-regulate the expression of Nrf2-dependent gene products.