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The value of proteasome inhibition in cancer

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DRUG DISCOVERY TODAY
卷 13, 期 15-16, 页码 716-722

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ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2008.05.003

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  1. Ministry of Education, Youth and Sports of the Czech Republic [MSM 6198959216]
  2. Grant Agency of the Czech Republic [GACR 303/08/P137]

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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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