Activators and Inhibitors of NRF2: A Review of Their Potential for Clinical Development

© 2019 Natalia Robledinos-Antón et al.The transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) triggers the first line of homeostatic responses against a plethora of environmental or endogenous deviations in redox metabolism, proteostasis, inflammation, etc. Therefore, pharmacological activation of NRF2 is a promising therapeutic approach for several chronic diseases that are underlined by oxidative stress and inflammation, such as neurodegenerative, cardiovascular, and metabolic diseases. A particular case is cancer, where NRF2 confers a survival advantage to constituted tumors, and therefore, NRF2 inhibition is desired. This review describes the electrophilic and nonelectrophilic NRF2 activators with clinical projection in various chronic diseases. We also analyze the status of NRF2 inhibitors, which at this time provide proof of concept for blocking NRF2 activity in cancer therapy.This work was supported by grants SAF2016-76520-R of the Spanish Ministry of Economy and Competitiveness, B2017/BMD-3827 of the Autonomous Community of Madrid, and P_37_732/2016 REDBRAIN of the European Regional Development Fund; Competitiveness Operational Program 2014-2020. NRA and RFG are recipients of FPU and FPI contracts, respectively, of the Spanish Ministry of Economy and Competitiveness