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Disulfiram + chelated zinc is a combination therapy involving the drug disulfiram and a supplemental form of bioavailable (chelated) zinc. Disulfiram is an aldehyde dehydrogenase inhibitor originally approved for the treatment of chronic alcoholism, where it works by causing unpleasant effects when alcohol is consumed. In addition to its established use in alcohol dependence, disulfiram has been repurposed for investigational uses in oncology and infectious diseases due to its ability to form metal complexes with divalent cations such as copper and zinc via its metabolite diethyldithiocarbamate (DDTC). When combined with chelated zinc, this therapy exploits the formation of a stable Zn-DDTC complex that exhibits potent cytotoxic activity against certain cancer cells and protozoan parasites. The mechanism involves inhibition of metalloproteases (such as CSN5), disruption of proteasome-mediated protein degradation, induction of oxidative stress through reactive oxygen species generation, alteration of intracellular metal homeostasis (notably increasing lysosomal sequestration of zinc), and impairment of essential enzymatic pathways in target cells. This combination has shown preclinical efficacy against disseminated melanoma and amebic infections (*Entamoeba histolytica*), with clinical trials completed or ongoing for refractory metastatic melanoma[3][5][6][9].
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