EN450 is a cysteine-reactive covalent molecular glue degrader targeting NF-κB. It interacts with allosteric C111 in the E2 ubiquitin ligase UBE2D that induces the ternary complex formation between UBE2D and NFKB1. It exhibits anti-proliferative effects through a Cullin E3 ligase and proteasome-dependent mechanism.