The value of proteasome inhibition in cancer. Can the old drug, disulfiram, have a bright new future as a novel proteasome inhibitor?
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
PubMed
18579431
DOI
10.1016/j.drudis.2008.05.003
PII: S1359-6446(08)00163-3
Knihovny.cz E-resources
- MeSH
- Bortezomib MeSH
- Disulfiram pharmacology therapeutic use MeSH
- Proteasome Inhibitors * MeSH
- Boronic Acids therapeutic use MeSH
- Humans MeSH
- Neoplasms drug therapy enzymology MeSH
- NF-kappa B metabolism MeSH
- Alcohol Deterrents pharmacology therapeutic use MeSH
- Forecasting MeSH
- Proteasome Endopeptidase Complex metabolism MeSH
- Antineoplastic Agents pharmacology therapeutic use MeSH
- Pyrazines therapeutic use MeSH
- Drug Screening Assays, Antitumor MeSH
- Thiocarbamates pharmacology therapeutic use MeSH
- Ubiquitin metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Bortezomib MeSH
- Disulfiram MeSH
- Proteasome Inhibitors * MeSH
- Boronic Acids MeSH
- NF-kappa B MeSH
- Alcohol Deterrents MeSH
- Proteasome Endopeptidase Complex MeSH
- Antineoplastic Agents MeSH
- Pyrazines MeSH
- Thiocarbamates MeSH
- Ubiquitin MeSH
The major approach to the development of anticancer drugs involves searching for new compounds, efficient against malignancies, which are not, as yet, used clinically. This strategy is time-consuming and expensive. Recent studies have disclosed a surprising, but mechanistically consistent, anticancer activity of disulfiram (antabuse), a drug used for about 50 years in the treatment of alcoholism. Disulfiram has been successfully used to suppress hepatic metastases originating from ocular melanoma. The pharmacokinetics of disulfiram and its pharmacological profile in cancer cell lines and in cancer cells obtained from patients is well known. Disulfiram is a readily available and inexpensive substance whose adverse effects are negligible, compared to classical cancerostatics. In addition, the inhibitory potency of disulfiram against the proteasome conforms to current anticancer strategies and represents a new, promising approach to proteasome inhibition.
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