Disulfiram is a copper and zinc chelator and an irreversible inhibitor of aldehyde dehydrogenase (IC50 = 0.1 mM) that has been indicated for the treatment of alcohol dependence. It also inhibits the copper-dependent enzyme dopamine β-hydroxylase, which prevents the breakdown of dopamine and has been considered as a treatment for cocaine dependence. When in complex with copper, disulfiram has been shown to inhibit purified 20S proteasome (IC50 = 7.5 μM) and 26S proteasome (IC50 = 20 μM) from MDA-MB-0231 breast cancer cells. Because disulfiram targets the ubiquitin-proteasome pathway, it has been investigated as an anti-cancer agent. Furthermore, at 250 nM it has been shown to induce reactive oxygen species, to activate JNK and p38 pathways, and to inhibit NF-κB activity, which suppresses self-renewal in cancer stem cells.
