A New Class of Molecular Glues: Double Allostery Restores KEAP1 Control of NRF2

Roy and colleagues describe VVD-065, a covalent allosteric molecular glue that binds KEAP1 at Cys151 to enhance KEAP1-CUL3 assembly, restore NRF2 ubiquitination and degradation, and selectively suppress NRF2-driven tumors by reactivating endogenous E3 ligase function. See related article by Roy et al., p. 953.