VVD 065 is an NRF2 inhibitor that functions through a covalent allosteric binding mechanism. It promotes the degradation of NRF2 by covalently bonding with C151 on KEAP1, thereby enhancing the formation of the KEAP1-CUL3 ubiquitin ligase complex. With potent target binding affinity (TE50 of 9 nM in KYSE70 cells) and selectivity for unrelated targets, VVD 065 effectively inhibits NRF2-associated cell growth.
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