Drug Discov Today.
2008 Aug;13(15-16):716-22. Epub 2008 Jun 23.
value of proteasome inhibition in cancer. Can the old drug, disulfiram,
have a bright new future as a novel proteasome inhibitor?
Department of Medical Chemistry and
Biochemistry at Palacky University, Hnevotinska 3, Olomouc 77515, Czech
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.