Abstract
Ribonucleotide reductase (RR) is a multisubunit enzyme responsible for the reduction of ribonucleotides to their corresponding deoxyribonucleotides, which are building blocks for DNA replication and repair. The key role of RR in DNA synthesis and cell growth control has made it an important target for anticancer therapy. Increased RR activity has been associated with malignant transformation and tumor cell growth. Efforts for new RR inhibitors have been made in basic and translational research. In recent years, several RR inhibitors, including Triapine, Gemcitabine, and GTI-2040, have entered clinical trial or application. Furthermore, the discovery of p53R2, a p53-inducible form of the small subunit of RR, raises the interest to develop subunit-specific RR inhibitors for cancer treatment. This review compiles recent studies on (1) the structure, function, and regulation of two forms of RR; (2) the role in tumorigenesis of RR and the effect of RR inhibition in cancer treatment; (3) the classification, mechanisms of action, antitumor activity, and clinical trial and application of new RR inhibitors that have been used in clinical cancer chemotherapy or are being evaluated in clinical trials; (4) novel approaches for future RR inhibitor discovery.
Keywords: Ribonucleotide reductase, structure and function, inhibitors, classification, mechanism of action, clinical trial and application, drug discovery
Current Cancer Drug Targets
Title: Ribonucleotide Reductase Inhibitors and Future Drug Design
Volume: 6 Issue: 5
Author(s): J. Shao, B. Zhou, Bernard Chu and Y. Yen
Affiliation:
Keywords: Ribonucleotide reductase, structure and function, inhibitors, classification, mechanism of action, clinical trial and application, drug discovery
Abstract: Ribonucleotide reductase (RR) is a multisubunit enzyme responsible for the reduction of ribonucleotides to their corresponding deoxyribonucleotides, which are building blocks for DNA replication and repair. The key role of RR in DNA synthesis and cell growth control has made it an important target for anticancer therapy. Increased RR activity has been associated with malignant transformation and tumor cell growth. Efforts for new RR inhibitors have been made in basic and translational research. In recent years, several RR inhibitors, including Triapine, Gemcitabine, and GTI-2040, have entered clinical trial or application. Furthermore, the discovery of p53R2, a p53-inducible form of the small subunit of RR, raises the interest to develop subunit-specific RR inhibitors for cancer treatment. This review compiles recent studies on (1) the structure, function, and regulation of two forms of RR; (2) the role in tumorigenesis of RR and the effect of RR inhibition in cancer treatment; (3) the classification, mechanisms of action, antitumor activity, and clinical trial and application of new RR inhibitors that have been used in clinical cancer chemotherapy or are being evaluated in clinical trials; (4) novel approaches for future RR inhibitor discovery.
Export Options
About this article
Cite this article as:
Shao J., Zhou B., Chu Bernard and Yen Y., Ribonucleotide Reductase Inhibitors and Future Drug Design, Current Cancer Drug Targets 2006; 6 (5) . https://dx.doi.org/10.2174/156800906777723949
DOI https://dx.doi.org/10.2174/156800906777723949 |
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
-
Persistent Current Blockers of Voltage-Gated Sodium Channels: A Clinical Opportunity for Controlling Metastatic Disease
Recent Patents on Anti-Cancer Drug Discovery Isolation and Boactivities of Furfuran Type Lignan Compounds from Edible Plants
Recent Patents on Food, Nutrition & Agriculture Cytotoxic Stilbenes and Derivatives as Promising Antimitotic Leads for Cancer Therapy
Current Pharmaceutical Design ICH Q8 Guidelines in Practice: Spray Drying Process Optimization by 2<sup>3</sup> Factorial Design for the Production of Famotidine Nanoparticles
Pharmaceutical Nanotechnology The Pilot Phase of the NIH Chemical Genomics Center
Current Topics in Medicinal Chemistry Synthesis of Quinazolines as Tyrosine Kinase Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Impaired Expression and Function of Signaling Pathway Enzymes by Anthocyanins: Role on Cancer Prevention and Progression
Current Enzyme Inhibition PI3K-Akt Signaling and Viral Infection
Recent Patents on Biotechnology Modulation of Regulatory T Cells in Health and Disease: Role of Toll-Like Receptors
Inflammation & Allergy - Drug Targets (Discontinued) Pretargeted Radioimmunotherapy with α-Particle Emitting Radionuclides
Current Radiopharmaceuticals New Issues about Nitric Oxide and its Effects on the Gastrointestinal Tract
Current Pharmaceutical Design Editorial (Thematic Issue: Recent Advances in Proteasome Inhibitor-Based Cancer Therapies)
Current Cancer Drug Targets Expression and Characterisation of Recombinant Molecules in Transgenic Soybean
Current Pharmaceutical Design Editorial [ Hot Topic-II: Zinc Metallo-Enzymes as Target for Drug Design (Guest Editor: Giuseppina De Simone )]
Current Medicinal Chemistry Meet Our Editorial Board Member
Anti-Cancer Agents in Medicinal Chemistry Exploration of (hetero)aryl Derived Thienylchalcones for Antiviral and Anticancer Activities
Medicinal Chemistry Editorial [Thematic Issue: Structural Characteristics of Short Peptides Solution Recombinant Therapeutic Protein Vaccines]
Protein & Peptide Letters Review of Medicinal Plants Common to Traditional Chinese and Indian Medicines with Relevance to Non-Communicable Diseases
Current Traditional Medicine Stem Cells: An Overview of the Current Status of Therapies for Central and Peripheral Nervous System Diseases
Current Medicinal Chemistry Immunosuppressive Properties of Mesenchymal Stem Cells: Advances and Applications
Current Molecular Medicine