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Disulfiram, and Disulfiram Derivatives as Novel Potential Anticancer Drugs Targeting the Ubiquitin Proteasome System in Both Preclinical and Clinical Studies

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Disulfiram is a FDA approved drug for the treatment of alcoholism and has been available for clinical use for over five decades. Despite data from the 1970s and 80s, which showed that disulfiram and analogs are able to enhance the activity of anticancer cytotoxic drugs and might be useful as chemopreventative agents, the underlying molecular mechanisms remained unknown until recently. Large scale screening efforts for agents that can inhibit the proteasome and be used as novel anticancer drugs revealed that disulfiram has proteasome inhibitory activity. Moreover, disulfiram was also found to have specific activity against zinc fingers and RING-finger ubiquitin E3 ligases that play an important role in cancer development. Here we review the preclinical and clinical studies exploring disulfiram as an anticancer agent, as well as research programs that focus on the development of disulfiram derivatives as inhibitors of the ubiquitinproteasome system.

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Keywords: Disulfiram; anticancer activity; clinical trials; copper; proteasome; ubiquitin E3 ligases; zinc; zinc ejection

Document Type: Research Article

Publication date: March 1, 2011

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  • Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes, genes.
    Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in cancer.
    As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.
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