Abstract
Nucleoside analogs serve as important chemotherapeutic agents in a number of severe diseases such as cancer and viral infections. These agents are pro-drugs that have to be taken up and phosphorylated in several steps to be trapped in the cells and transformed to active metabolites that inhibit essential steps in the replication of viruses or malignant cells. The anabolic deoxynucleoside kinases (dNKs) and catabolic 5'-nucleotidases(5'-NTs) are involved in maintaining substrate cycles, and act as regulators for the intracellular pools of active nucleotide metabolites. In this chapter the expression patterns of the four dNKs i.e.cytosolic deoxycytidine kinase (dCK) and thymidine kinase 1 (TK1) and the mitochondrial thymidine kinase 2 (TK2) and deoxyguanosine kinase (dGK) as well as the six intracellular 5'-NTs: cN-IA, cN-IB, cN-II, cN-III, cdN, mdN, present in animal cells and tissues will be described. Their role as primary controllers of the accumulation and activation of important anti viral and anti cancer nucleoside analogs in different tissues involved in the pathophysiology of these diseases will be evaluated. The predictability of using the ratios between the activities of the dNKs and 5'-NTs for estimating efficacy and side effects of nucleoside drug candidates will be discussed as well as recommendations on how to use this information to improve future therapies with nucleoside drugs.
Keywords: Nucleoside analogs, deoxynucleoside kinases, 5’-nucleotidases, cell culture models, tissues extracts, efficacy, toxicity.
Current Medicinal Chemistry
Title:Is the Expression of Deoxynucleoside Kinases and 5'-nucleotidases in Animal Tissues Related to the Biological Effects of Nucleoside Analogs?
Volume: 20 Issue: 34
Author(s): Staffan Eriksson
Affiliation:
Keywords: Nucleoside analogs, deoxynucleoside kinases, 5’-nucleotidases, cell culture models, tissues extracts, efficacy, toxicity.
Abstract: Nucleoside analogs serve as important chemotherapeutic agents in a number of severe diseases such as cancer and viral infections. These agents are pro-drugs that have to be taken up and phosphorylated in several steps to be trapped in the cells and transformed to active metabolites that inhibit essential steps in the replication of viruses or malignant cells. The anabolic deoxynucleoside kinases (dNKs) and catabolic 5'-nucleotidases(5'-NTs) are involved in maintaining substrate cycles, and act as regulators for the intracellular pools of active nucleotide metabolites. In this chapter the expression patterns of the four dNKs i.e.cytosolic deoxycytidine kinase (dCK) and thymidine kinase 1 (TK1) and the mitochondrial thymidine kinase 2 (TK2) and deoxyguanosine kinase (dGK) as well as the six intracellular 5'-NTs: cN-IA, cN-IB, cN-II, cN-III, cdN, mdN, present in animal cells and tissues will be described. Their role as primary controllers of the accumulation and activation of important anti viral and anti cancer nucleoside analogs in different tissues involved in the pathophysiology of these diseases will be evaluated. The predictability of using the ratios between the activities of the dNKs and 5'-NTs for estimating efficacy and side effects of nucleoside drug candidates will be discussed as well as recommendations on how to use this information to improve future therapies with nucleoside drugs.
Export Options
About this article
Cite this article as:
Eriksson Staffan, Is the Expression of Deoxynucleoside Kinases and 5'-nucleotidases in Animal Tissues Related to the Biological Effects of Nucleoside Analogs?, Current Medicinal Chemistry 2013; 20 (34) . https://dx.doi.org/10.2174/0929867311320340004
DOI https://dx.doi.org/10.2174/0929867311320340004 |
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
- 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
-
Voltage-Gated Ion Channels, New Targets in Anti-Cancer Research
Recent Patents on Anti-Cancer Drug Discovery Radiation Protection of the Child from Diagnostic Imaging
Current Pediatric Reviews Notch Signaling Proteins: Legitimate Targets for Cancer Therapy
Current Protein & Peptide Science Novel Inhibitors of Inosine Monophosphate Dehydrogenase in Patent Literature of the Last Decade
Recent Patents on Anti-Cancer Drug Discovery The Akt Pathway: Molecular Targets for Anti-Cancer Drug Development
Current Cancer Drug Targets Aptamer-Mediated Cancer Gene Therapy
Current Gene Therapy Luteolin, a Flavonoid with Potential for Cancer Prevention and Therapy
Current Cancer Drug Targets The Effects of Cantharidin and Cantharidin Derivates on Tumour Cells
Anti-Cancer Agents in Medicinal Chemistry What Western Pharmacists Need to Know About Traditional Chinese Medicine; A Canadian Perspective
Current Traditional Medicine Clinical Applicability of Microarray Technology in the Diagnosis, Prognostic Stratification, Treatment and Clinical Surveillance of Cervical Adenocarcinoma
Current Pharmaceutical Design Hemopoiesis in Ph-Negative Chronic Myeloproliferative Disorders
Current Stem Cell Research & Therapy Internal Ribosome Entry Site Elements in Eukaryotic Genomes
Current Genomics Immunotherapeutic and Immunoregulatory Drugs in Haematologic Malignancies
Current Topics in Medicinal Chemistry Epigenetic Multiple Modulators
Current Topics in Medicinal Chemistry Natural Product Origins of Hsp90 Inhibitors
Current Cancer Drug Targets Is there a Possible Single Mediator in Modulating Neuroendocrine–thymus Interaction in Ageing?
Current Aging Science Natural Products Chemistry in Marine Ascidians of the Genus Aplidium
Mini-Reviews in Organic Chemistry Old Tyrosine Kinase Inhibitors and Newcomers in Gastrointestinal Cancer Treatment
Current Cancer Drug Targets Making Sense of Molecular Signatures in The Immune System
Combinatorial Chemistry & High Throughput Screening Recent Patents Concerning Diagnostic and Therapeutic Applications of Aberrantly Methylated Sequences in Pancreatic Cancer
Recent Patents on DNA & Gene Sequences