Abstract
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.
Keywords: Disulfiram, proteasome, ubiquitin E3 ligases, zinc ejection, zinc, copper, anticancer activity, clinical trials
Current Cancer Drug Targets
Title: Disulfiram, and Disulfiram Derivatives as Novel Potential Anticancer Drugs Targeting the Ubiquitin Proteasome System in Both Preclinical and Clinical Studies
Volume: 11 Issue: 3
Author(s): F. R. Kona, D. Buac and A. M. Burger
Affiliation:
Keywords: Disulfiram, proteasome, ubiquitin E3 ligases, zinc ejection, zinc, copper, anticancer activity, clinical trials
Abstract: 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.
Export Options
About this article
Cite this article as:
R. Kona F., Buac D. and M. Burger A., Disulfiram, and Disulfiram Derivatives as Novel Potential Anticancer Drugs Targeting the Ubiquitin Proteasome System in Both Preclinical and Clinical Studies, Current Cancer Drug Targets 2011; 11 (3) . https://dx.doi.org/10.2174/156800911794519798
DOI https://dx.doi.org/10.2174/156800911794519798 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Design of Novel Chemotherapeutic Agents Targeting Checkpoint Kinase 1 Using 3D-QSAR Modeling and Molecular Docking Methods
Current Computer-Aided Drug Design Angiogenesis: A Target for Cancer Therapy
Current Pharmaceutical Design Pieces of the Complex Puzzle of Cancer Cell Energy Metabolism: An Overview of Energy Metabolism and Alternatives for Targeted Cancer Therapy
Current Medicinal Chemistry Physiology of Folic Acid in Health and Disease
Current Drug Metabolism The Cyclin-Dependent Kinase Inhibitor p21CDKN1A as a Target of Anti-Cancer Drugs
Current Cancer Drug Targets Mitochondria: A Promising Target for Anticancer Alkaloids
Current Topics in Medicinal Chemistry Nanoliposome is a Promising Carrier of Protein and Peptide Biomolecule for the Treatment of Cancer
Anti-Cancer Agents in Medicinal Chemistry Recent Patents on Influenza Vaccines
Recent Patents on Biotechnology The Akt Pathway: Molecular Targets for Anti-Cancer Drug Development
Current Cancer Drug Targets Tumor Specific Novel Taxoid-Monoclonal Antibody Conjugates
Current Medicinal Chemistry Current Status of Magnetite-Based Core@Shell Structures for Diagnosis and Therapy in Oncology Short running title: Biomedical Applications of Magnetite@Shell Structures
Current Pharmaceutical Design Non-Surgical Treatment Options for Symptomatic Uterine Leiomyomas
Current Women`s Health Reviews Quercetin as a Systemic Chemopreventative Agent: Structural and Functional Mechanisms
Mini-Reviews in Medicinal Chemistry Combination of Phytochemicals as Adjuvants for Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Therapeutic Targeting of CPT-11 Induced Diarrhea: A Case for Prophylaxis
Current Drug Targets Antitumor Activity of Cyclodextrin-based Supramolecular Platinum Prodrug In vitro and In vivo
Letters in Drug Design & Discovery Immune Responses to Adeno-Associated Virus Vectors
Current Gene Therapy Editorial [Hot Topic: Tumor Immunology (Guest Editors: Bharat H. Joshi and Raj K. Puri)]
Current Molecular Medicine Recent Advances in Biotransformation by Cunninghamella Species
Current Drug Metabolism HIF-1 Inhibitors for Cancer Therapy: From Gene Expression to Drug Discovery
Current Pharmaceutical Design