793719-01-4

EN450 is a cysteine-reactive covalent molecular glue degrader targeting NF-κB. EN450 interacts with allosteric C111 in the E2 ubiquitin ligase UBE2D. EN450 induces the ternary complex formation between UBE2D and NFKB1. EN450 exerts its anti-proliferative effects through a Cullin E3 ligase and proteasome-dependent mechanism[1].

EN450 is a molecular glue degraders of the oncogenic transcription factor NFKB1 th at induces ternary complex formation between ubiquitin-conjugating enzyme E2D1 (UBE2D1) and NFKB1. EN450 covalently modifies an allosteric C111 in UBE2D1 and significantly reduces NFKB1 p105 levels. It impairs leukemia cell viability in a NEDDylation and proteasome-dependent manner at 50 μM.

[1] King EA, et al. Chemoproteomics-enabled discovery of a covalent molecular glue degrader targeting NF-κB. Cell Chem Biol. 2023 Apr 20;30(4):394-402.e9. DOI:10.1016/j.chembiol.2023.02.008