Abstract
Benzamide riboside (BR), a synthetic C-nucleoside, acts as a strong growth inhibitor of cancer cells in vitro and in vivo. BR, like TR and related nucleoside prodrugs, act by anabolism to NAD analogs. These analogs selectively inhibit IMPDH, leading to depletion of cellular GTP, growth cessation, and cell differentiation. To date only preclinical studies have been carried out. However, in tiazofurin (TR), a related drug, phase I / II clinical trials have been conducted in patients with acute leukemia and shown to be a very promising agent with a response rate of 85percent in 26 patients in one of the trials. Tiazofurin is now undergoing phase III clinical trials as a result. Dose limiting toxicity of tiazofurin was headache, somnolence and nausea with no myelosuppression noted. By contrast, BR showed skeletal muscle toxicity, hepatotoxicity and myelosuppression in preclinical data. Skeletal muscle toxicity was noted in the paraspinal muscles and may represent dose-limiting toxicity. Since BR does exhibit myelosuppression, the most common chemotherapy-related side effect in humans, careful judgment is warranted should BR be included in multidrug regimens, although BRs potent cytotoxicity to tumor cells in preclinical models still makes it a promising drug.
Keywords: c-nucleoside, benzamide riboside, cancer chemotherapy, toxicity, apoptosis
Current Medicinal Chemistry
Title: Toxicity and Efficacy of Benzamide Riboside in Cancer Chemotherapy Models
Volume: 9 Issue: 7
Author(s): Hiremagalur N. Jayaram, Joel A. Yalowitz, Francisco Arguello and John F. Greene,Jr
Affiliation:
Keywords: c-nucleoside, benzamide riboside, cancer chemotherapy, toxicity, apoptosis
Abstract: Benzamide riboside (BR), a synthetic C-nucleoside, acts as a strong growth inhibitor of cancer cells in vitro and in vivo. BR, like TR and related nucleoside prodrugs, act by anabolism to NAD analogs. These analogs selectively inhibit IMPDH, leading to depletion of cellular GTP, growth cessation, and cell differentiation. To date only preclinical studies have been carried out. However, in tiazofurin (TR), a related drug, phase I / II clinical trials have been conducted in patients with acute leukemia and shown to be a very promising agent with a response rate of 85percent in 26 patients in one of the trials. Tiazofurin is now undergoing phase III clinical trials as a result. Dose limiting toxicity of tiazofurin was headache, somnolence and nausea with no myelosuppression noted. By contrast, BR showed skeletal muscle toxicity, hepatotoxicity and myelosuppression in preclinical data. Skeletal muscle toxicity was noted in the paraspinal muscles and may represent dose-limiting toxicity. Since BR does exhibit myelosuppression, the most common chemotherapy-related side effect in humans, careful judgment is warranted should BR be included in multidrug regimens, although BRs potent cytotoxicity to tumor cells in preclinical models still makes it a promising drug.
Export Options
About this article
Cite this article as:
Jayaram N. Hiremagalur, Yalowitz A. Joel, Arguello Francisco and Greene,Jr F. John, Toxicity and Efficacy of Benzamide Riboside in Cancer Chemotherapy Models, Current Medicinal Chemistry 2002; 9 (7) . https://dx.doi.org/10.2174/0929867024606858
DOI https://dx.doi.org/10.2174/0929867024606858 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
![](/images/wayfinder.jpg)
- 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
- Announcements
Related Articles
-
The Quest for a Tumor Suppressor Gene Phenotype
Current Molecular Medicine Oligonucleotides and G-quadruplex Stabilizers: Targeting Telomeres and Telomerase in Cancer Therapy
Current Pharmaceutical Design Antitumor Activity and Structure-Activity Relationship of Diterpenoids with a Dehydroabietyl Skeleton
Combinatorial Chemistry & High Throughput Screening Novel Anticancer Targets and Drug Discovery in Post Genomic Age
Current Medicinal Chemistry - Anti-Cancer Agents Activatable Optical Probes for the Detection of Enzymes
Current Organic Synthesis Heat Shock Proteins in Cancer: Signaling Pathways, Tumor Markers and Molecular Targets in Liver Malignancy
Protein & Peptide Letters Proteomics and Epigenetic Mechanisms in Stem Cells
Current Proteomics Role of Extracellular Vesicles in Glioma Progression: Deciphering Cellular Biological Processes to Clinical Applications
Current Topics in Medicinal Chemistry Heme Oxygenase-1 in Tumor Biology and Therapy
Current Drug Targets Genetic Chemoprotection with Mutant O6-Alkylguanine-DNA-Alkyltransferases
Current Gene Therapy Na<sup>+</sup>/K<sup>+</sup> ATPase Inhibitors in Cancer
Current Drug Targets Tumor Protein p63/microRNA Network in Epithelial Cancer Cells
Current Genomics Cationic Polymers and their Self-Assembly for Antibacterial Applications
Current Topics in Medicinal Chemistry The Chemopreventive and Chemotherapeutic Potentials of Tea Polyphenols
Current Pharmaceutical Biotechnology IAPs, their Antagonists and their Role in Neurological Disease and Cancer
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Stem Cell-Mediated Delivery of Therapies in the Treatment of Glioma
Mini-Reviews in Medicinal Chemistry Manipulation of Glycolysis in Malignant Tumors: Fantasy or Therapy?
Current Medicinal Chemistry Metabolic Features of Melanoma: A Gold Mine of New Therapeutic Targets?
Current Cancer Drug Targets AGE-RAGE System and Carcinogenesis
Current Pharmaceutical Design Natural Sirtuin Modulators in Drug Discovery: A Review (2010 -2020)
Current Medicinal Chemistry