Abstract
Background: Modified nucleoside and nucleotide analogs are now the cornerstone of antiviral and anticancer chemotherapies. However, these compounds are not active on their own and need, after entering the cell, to be metabolized to their active 5'-triphosphate form.
Methods: Limitations of these metabolic processes led to development of nucleoside/nucleotide prodrugs in which nucleosides are masked with different groups that can be intracellularly cleaved either chemically or enzymatically.
Results: Several prodrug approaches have been successfully developed in order to increase the efficacy, bioavailability, penetration in target organ, and selectivity of nucleoside/nucleotide analogs.
Conclusion: The concept of nucleoside/nucleotide prodrug is now a well-established approach that led to the approval of numerous drugs for the treatment of HIV, HBV, HCV, HSV and cancer.
Keywords: Antiviral agents, prodrug, nucleoside, enzyme, monophosphate, triphosphate.
Current Pharmaceutical Design
Title:Metabolism of Nucleosides and Nucleotides Prodrugs
Volume: 23 Issue: 45
Author(s): Coralie De Schutter, Maryam Ehteshami, Emily T. Hammond, Franck Amblard and Raymond F. Schinazi*
Affiliation:
- Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta,United States
Keywords: Antiviral agents, prodrug, nucleoside, enzyme, monophosphate, triphosphate.
Abstract: Background: Modified nucleoside and nucleotide analogs are now the cornerstone of antiviral and anticancer chemotherapies. However, these compounds are not active on their own and need, after entering the cell, to be metabolized to their active 5'-triphosphate form.
Methods: Limitations of these metabolic processes led to development of nucleoside/nucleotide prodrugs in which nucleosides are masked with different groups that can be intracellularly cleaved either chemically or enzymatically.
Results: Several prodrug approaches have been successfully developed in order to increase the efficacy, bioavailability, penetration in target organ, and selectivity of nucleoside/nucleotide analogs.
Conclusion: The concept of nucleoside/nucleotide prodrug is now a well-established approach that led to the approval of numerous drugs for the treatment of HIV, HBV, HCV, HSV and cancer.
Export Options
About this article
Cite this article as:
De Schutter Coralie, Ehteshami Maryam, Hammond T. Emily, Amblard Franck and Schinazi F. Raymond *, Metabolism of Nucleosides and Nucleotides Prodrugs, Current Pharmaceutical Design 2017; 23 (45) . https://dx.doi.org/10.2174/1381612823666171011104158
DOI https://dx.doi.org/10.2174/1381612823666171011104158 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- 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
-
Obesity in the Cardiovascular Continuum
Current Clinical Pharmacology Acute Actions of Natriuretic Peptides in Coronary Vasculature and Ischaemic Myocardium
Current Pharmaceutical Design Effect of a New Class of Compounds of the Group of Substituted 5R1, 6H2-1,3,4-thiadiazine-2-amines on the Inflammatory and Cytokine Response in Experimental Myocardial Infarction
Current Vascular Pharmacology Clinical Approaches Toward Tumor Angiogenesis: Past, Present and Future
Current Pharmaceutical Design Old And New Oral Anticoagulants In Management Of Atrial Fibrillation: A Double-Edged Sword For Women
Current Vascular Pharmacology Metalloprotein Inhibitors for the Treatment of Human Diseases
Current Topics in Medicinal Chemistry Novel oral Anticoagulants in Non-Valvular Atrial Fibrillation
Cardiovascular & Hematological Agents in Medicinal Chemistry Innovative Therapeutic Potential of Cannabinoid Receptors as Targets in Alzheimer’s Disease and Less Well-Known Diseases
Current Medicinal Chemistry Current Concepts of Immunopathogenesis, Diagnosis and Therapy in Whipples Disease
Current Medicinal Chemistry Immunomodulation Mechanism of Antidepressants: Interactions between Serotonin/Norepinephrine Balance and Th1/Th2 Balance
Current Neuropharmacology The Spatial QRS-T Angle: Implications in Clinical Practice
Current Cardiology Reviews Extranuclear Effects of Thyroid Hormones in Skeletal Muscle
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Mitochondrial Dysfunction and Antioxidant Therapy in Sepsis
Infectious Disorders - Drug Targets Pharmacological Manipulation of Peripheral Vascular Resistance in Single Ventricle Patients (Stages I, II, and III of Palliation)
Current Vascular Pharmacology Angiotensin 1-7 Promotes Cardiac Angiogenesis Following Infarction
Current Vascular Pharmacology Safety Issues of Vitamin D Supplementation
Anti-Cancer Agents in Medicinal Chemistry Targeting Chemokine Receptor CXCR4 for Treatment of HIV-1 Infection, Tumor Progression, and Metastasis
Current Topics in Medicinal Chemistry Mitochondrial Oxidative Stress and Heart Failure ∼Novel Pathophysiological Insight and Treatment Strategies∼
Current Cardiology Reviews Diabetes and Nutritional Screening in Post-Bariatric Patients
Current Diabetes Reviews Part 1: The Wider Considerations in Translating Heart Failure Guidelines
Current Cardiology Reviews