Bis(diethyldithiocarbamato)copper(II) (CuET)

Bis(diethyldithiocarbamato)copper(II), commonly known as CuET, is a metal-organic complex that serves as the primary active metabolite responsible for the anticancer activity of the alcohol-aversion drug disulfiram (Antabuse). It forms in vivo when disulfiram is reduced to diethyldithiocarbamate (DTC), which then chelates endogenous copper ions into a stable square-planar coordination environment (Skrott et al., Nature, 2017). Although CuET is a chemical complex rather than a biological receptor, it acts as a potent pharmacological agent by specifically targeting the Nuclear protein localization protein 4 (NPL4). By binding to the zinc-finger domains of NPL4, CuET induces protein aggregation and disables the p97/VCP segregase machinery, a critical component of the ubiquitin-proteasome system required for protein quality control. This disruption leads to a massive accumulation of misfolded proteins and triggers apoptosis in cancer cells, which often exhibit a high dependency on the p97 pathway and elevated copper levels (Skrott et al., Nature, 2017; PubChem CID 167304).

Other names

Cu(DTC)2Copper(II) diethyldithiocarbamateCu-DTCBis(diethyldithiocarbamate)copper

CuET acts as the active metabolite of disulfiram; it binds to the zinc-finger domains of the NPL4 protein, inducing its aggregation and disabling the p97/VCP segregase machinery, which leads to proteotoxic stress and cell death.