NAcM-OPT

NAcM-OPT (2089293-61-6) is a potent and selective NEDD8 ligation inhibitor, IC50=80 nM (in vitro).1 It inhibits the N-terminal acetyl-dependent interaction between the E2 conjugating enzyme UBE2M/UBC12 and DCN1, a subunit of a multiprotein E3 ligase for the ubiquitin-like protein NEDD8, an interaction which is essential for assembly of the multiprotein ligation complex.2 NAcM-OPT inhibits NEDD8 ligation in vitro and in cells (IC50=10 μM) and suppresses anchorage-independent growth of HCC95 cells and is highly selective with respect to other N-terminal acetyl protein binding sites.1

NAcM-OPT inhibits N-Acetyl-mediated interaction between BE2M (E2 conjugating enzyme) and DCN1 (a component of E3 ligase complex). Also has inhibitory action on DCN2 and NEDD8 ubiquitin-like protein. Reduces anchorage-independent growth in DCN1-amplified cell line.

ChEBI: 1-Benzyl-1-(1-butyl-4-piperidinyl)-3-(3,4-dichlorophenyl)urea is a member of ureas.

[1] DANIEL C SCOTT. Blocking an N-terminal acetylation–dependent protein interaction inhibits an E3 ligase[J]. Nature chemical biology, 2017, 13 8: 850-857. DOI:10.1038/nchembio.2386
[2] DANIEL C. SCOTT. N-Terminal Acetylation Acts as an Avidity Enhancer Within an Interconnected Multiprotein Complex[J]. Science, 2011, 334 6056. DOI:10.1126/science.1209307