Document Detail


Disulfiram, and disulfiram derivatives as novel potential anticancer drugs targeting the ubiquitin-proteasome system in both preclinical and clinical studies.
MedLine Citation:
PMID:  21247383     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Disulfiram is a FDA approved drug for the treatment of alcoholism and available for clinical use since over 5 decades. Despite data from the 1970s and 80s that showed that disulfiram and analogs are able to enhance the activity of anticancer cytotoxic drugs and might be useful 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 ubiquitin-proteasome system.
Authors:
F R Kona; D Buac; A M Burger
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Current cancer drug targets     Volume:  11     ISSN:  1873-5576     ISO Abbreviation:  Curr Cancer Drug Targets     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-14     Completed Date:  2011-07-07     Revised Date:  2012-08-20    
Medline Journal Info:
Nlm Unique ID:  101094211     Medline TA:  Curr Cancer Drug Targets     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  338-46     Citation Subset:  IM    
Affiliation:
Barbara Ann Karmanos Cancer Institute and Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / therapeutic use*
Clinical Trials as Topic
Disulfiram / therapeutic use*
Drug Evaluation, Preclinical
Humans
Neoplasms / drug therapy*,  metabolism
Protease Inhibitors / therapeutic use*
Proteasome Endopeptidase Complex / drug effects*
Grant Support
ID/Acronym/Agency:
R01CA127258/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Protease Inhibitors; 97-77-8/Disulfiram; EC 3.4.25.1/Proteasome Endopeptidase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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