Advances and challenges in therapeutic targeting of NRF2

Activation of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is emerging as an attractive therapeutic approach to counteract oxidative stress, inflammation, and metabolic imbalances. These processes underpin many chronic pathologies with unmet therapeutic needs, including neurodegenerative disorders and metabolic diseases. As the NRF2 field transitions into the clinical phase of its evolution, the need for an understanding of the factors influencing NRF2 pharmacology has never been greater. In this opinion article we describe the rationale for targeting NRF2, summarise the recent advances in drug development of NRF2 modulators, and reflect on the remaining challenges in realising the full clinical potential of NRF2 as a therapeutic target.