The Promiscuity of Disulfiram in Medicinal Research

ACS Med Chem Lett. 2023 Nov 7;14(12):1610-1614. doi: 10.1021/acsmedchemlett.3c00450. eCollection 2023 Dec 14.

Abstract

Recent efforts to repurpose disulfiram, a drug used in alcohol-aversion therapy for decades, for other diseases suggest the molecule is almost an in vitro panacea: it seems to be effective against various cancers (by multiple mechanisms of action), Alzheimer's disease, obesity and metabolic syndrome, pythiosis, lyme borreliosis, COVID-19, and sepsis. The problem is that the molecule almost does not exist in the body after ingestion and, most importantly, is not the pharmacologically active entity in alcoholic patients, being rather a prodrug. This prodrug is widely and misleadingly used in many in vitro and in vivo experiments regardless of its physiologically reachable concentration or its metabolism in vivo.