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Curr Opin Chem Biol. 2011 Feb;15(1):162-73. doi: 10.1016/j.cbpa.2010.12.009. Epub 2010 Dec 30.

Small molecule modulators of antioxidant response pathway.

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Department of Cancer Biology, Dana-Farber Cancer Institute, 250 Longwood Ave, Boston, MA 02115, USA.


Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that regulates Antioxidant Response Element (ARE)-mediated transcription of a plethora of antioxidant and protective genes to counteract the harmful effects of reactive oxygen species or environmental carcinogens. Studies have demonstrated that pre-emptive activation of the Nrf2-ARE pathway reinforces the cellular defense mechanism against oxidative stress and leads to protection in a variety of disease models. Non-carcinogenic ARE inducers have been identified from a variety of chemical classes that enhance the transcriptional activity of Nrf2 through S-alkylation of reactive cysteines within the cellular redox sensor protein Keap1 (Kelch-like ECH associated protein 1). Here we review the currently known small molecule ARE inducers and their reported biological activities in various models.

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