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
-
Role of Alterations in the Apoptotic Machinery in Sensitivity of Cancer Cells to Treatment
Current Pharmaceutical Design Antioxidant Properties of Hydroxycinnamic Acids: A Review of Structure- Activity Relationships
Current Medicinal Chemistry Recent Advances in Use of Topoisomerase Inhibitors in Combination Cancer Therapy
Current Topics in Medicinal Chemistry Synthesis, Molecular Docking Study and in vitro Anticancer Activity of Tetrazole Linked Benzochromene Derivatives
Anti-Cancer Agents in Medicinal Chemistry Patent Selections
Recent Patents on DNA & Gene Sequences Proteasome Inhibitors in Cancer Therapy
Current Drug Targets 5-HT3 Receptors
Current Drug Targets - CNS & Neurological Disorders Amaranth: A Pseudo-Cereal with Nutraceutical Properties
Current Nutrition & Food Science Caspase-Independent Pathways of Programmed Cell Death: The Unraveling of New Targets of Cancer Therapy?
Current Cancer Drug Targets Radioimmunotherapy of Solid Tumors: Searching for the Right Target
Current Drug Delivery Anticarcinogenic Effects of Capsaicin-Loaded Nanoparticles on In vitro Hepatocellular Carcinoma
Current Chemical Biology Benzothiazole: A Versatile and Multitargeted Pharmacophore in the Field of Medicinal Chemistry
Letters in Organic Chemistry Interactome Analysis of the Differentially Expressed Proteins in Uterine Leiomyoma
Anti-Cancer Agents in Medicinal Chemistry Biomolecules Linked to Transition Metal Complexes - New Chances for Chemotherapy
Current Medicinal Chemistry Morin Inhibits Ovarian Cancer Growth through the Inhibition of NF-κB Signaling Pathway
Anti-Cancer Agents in Medicinal Chemistry Protein Kinases as Tumor Biomarkers and Therapeutic Targets
Current Pharmaceutical Design Synthesis and in vitro Anti-tumor Activity of Some New Sebacoyl Chloride Based Heterocycles
Current Organic Synthesis Oxaliplatin-induced Hyperexcitation of Rat Sciatic Nerve Fibers: An Intra-axonal Study
Anti-Cancer Agents in Medicinal Chemistry Cryptotanshinone Induces Pro-death Autophagy through JNK Signaling Mediated by Reactive Oxygen Species Generation in Lung Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Hitting the Golden TORget: Curcumin’s Effects on mTOR Signaling
Anti-Cancer Agents in Medicinal Chemistry