The Promiscuity of Disulfiram in Medicinal Research
Open accessAbstract
High Resolution Image Download MS PowerPoint Slide 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 .
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These characteristics reduce pharmaceutical industry incentives to fund expensive, large-scale clinical trials, creating a gap between preclinical findings and the evidence required for regulatory approval of new indications.
“However, these same characteristics reduce pharmaceutical industry incentives to fund expensive, large-scale clinical trials, creating a gap between preclinical findings and the evidence required for regulatory approval of new indications.156,157”
From Off-label and repurposed use of disulfiram beyond alcohol dependence: A systematic review of clinical and preclinical evidence (2026) · cites this paper as [157]
The ‘Repurposing the Drug in Clinical Trials’ section discusses in vitro research and two phase II cancer trials; the Conclusion calls for more physiologically meaningful evidence. Neither section addresses pharmaceutical-industry incentives, funding for large-scale trials, or the evidence needed for regulatory approval. Searches for those financial and regulatory points found no supporting passage in our copy. (LLM, conf=0.75)
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Self-citation
- Authors
- Cvek, B.
- Affiliations
- Palacký University Olomouc (CZ)
- Corresponding author
- Cvek, Boris
- ORCID
- Cvek, Boris
- Venue
- ACS Medicinal Chemistry Letters
- Publisher
- American Chemical Society (ACS)
- Published
- 2023-11-07
- Volume
- 14
- Issue
- 12
- Pages
- 1610-1614
- ISSN
- 1948-5875 (ISSN-L)
- PMC
- PMC10726457
- OpenAlex
- W4388465297
- Cited by
- 21
- References
- 29
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 6 · 2023: 1
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- ACS Medicinal Chemistry Letters (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- disulfiram, drug repurposing, prodrugs, pharmacological activity, cancer, Alzheimer's disease, obesity, metabolic syndrome, pythiosis, Lyme disease, COVID-19 pandemic, sepsis, in vitro drug testing, alcohol aversion therapy
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