Conditional NRF2 activator for oxidative stress disorders

A prodrug form of monomethyl fumarate (MMF) that selectively unmasks the redox-regulating nuclear receptor NRF2 at sites of oxidative stress via a Baeyer–Villiger oxidation reaction could help treat pain and other oxidative stress disorders without the systemic side effects of marketed NRF2 activators.

An in vitro screen of three synthesized MMF prodrugs identified an α-ketoester-based candidate that activated NRF2 reporter activity in the presence of pathological but not physiological levels of peroxides and peroxynitrite. ...