Abstract
Thymidylate kinase (TMPK) is a key enzyme for pyrimidine synthesis that catalyzes the phosphorylation of thymidine 5’-monophosphate (dTMP) in the presence of ATP and Mg2+ to form thymidine 5’-diphosphate (dTDP), which is then converted to thymidine 5’-triphosphate (dTTP) by nucleoside-diphosphate kinase (NDK). TMPK has an important function in cell proliferation and its enzyme kinetics and related structures have been determined in various organisms. TMPK is well recognized as a potential drug target, with the most notable function being in the activation of anti-HIV nucleoside prodrugs. Recent studies have shown that TMPK is a validated target for antibiotic development against grampositive bacterium of Staphylococcus aureus. In addition, inhibition of human TMPK increases the potential of anticancer agent doxorubicin toward colon cancer cells regardless of p53 status. Following the rapid expanding knowledge on TMPKs and the rising interests in TMPKs as a drug target, in this review we try to describe current research on TMPKs in various organisms of eukaryotes, prokaryotes and viruses and to provide information for designing new potential inhibitors against TMPKs.
Keywords: AZTMP, cancer chemotherapy, infectious disease, thymidylate kinase, TMPK assay, TMPK inhibitor
Current Medicinal Chemistry
Title:Thymidylate Kinase: An Old Topic Brings New Perspectives
Volume: 20 Issue: 10
Author(s): Q. Cui, W. S. Shin, Y. Luo, J. Tian, H. Cui and D. Yin
Affiliation:
Keywords: AZTMP, cancer chemotherapy, infectious disease, thymidylate kinase, TMPK assay, TMPK inhibitor
Abstract: Thymidylate kinase (TMPK) is a key enzyme for pyrimidine synthesis that catalyzes the phosphorylation of thymidine 5’-monophosphate (dTMP) in the presence of ATP and Mg2+ to form thymidine 5’-diphosphate (dTDP), which is then converted to thymidine 5’-triphosphate (dTTP) by nucleoside-diphosphate kinase (NDK). TMPK has an important function in cell proliferation and its enzyme kinetics and related structures have been determined in various organisms. TMPK is well recognized as a potential drug target, with the most notable function being in the activation of anti-HIV nucleoside prodrugs. Recent studies have shown that TMPK is a validated target for antibiotic development against grampositive bacterium of Staphylococcus aureus. In addition, inhibition of human TMPK increases the potential of anticancer agent doxorubicin toward colon cancer cells regardless of p53 status. Following the rapid expanding knowledge on TMPKs and the rising interests in TMPKs as a drug target, in this review we try to describe current research on TMPKs in various organisms of eukaryotes, prokaryotes and viruses and to provide information for designing new potential inhibitors against TMPKs.
Export Options
About this article
Cite this article as:
Cui Q., S. Shin W., Luo Y., Tian J., Cui H. and Yin D., Thymidylate Kinase: An Old Topic Brings New Perspectives, Current Medicinal Chemistry 2013; 20 (10) . https://dx.doi.org/10.2174/0929867311320100006
DOI https://dx.doi.org/10.2174/0929867311320100006 |
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
-
Exploring the Binding Affinity of Novel Syringic Acid Analogues and Critical Determinants of Selectivity as Potent Proteasome Inhibitors
Anti-Cancer Agents in Medicinal Chemistry In Vitro Inhibition Effect and Molecular Docking Study of Curcumin, Resveratrol, and Quercetin on Human Erythrocyte Glutathione Transferase
Current Enzyme Inhibition Biological Interfacial Engineering for Metastatic Cancer Diagnosis and Intervention
Current Medicinal Chemistry Controlled Release of Insulin in Blood from Strontium-Substituted Carbonate Apatite Complexes
Current Drug Delivery Development and Production of Commercial Therapeutic Monoclonal Antibodies in Mammalian Cell Expression Systems: An Overview of the Current Upstream Technologies
Current Pharmaceutical Biotechnology ZnS Nanoparticles: An Efficient Catalyst for the One-Pot Synthesis of Spiro [Pyrrolidine-2, 3'-Oxindole] Derivatives from Phenothiazinyl Chalcones
Letters in Organic Chemistry Microwave-Assisted Solvent-Free Synthesis of N-alkyl Benzotriazole Derivatives: Antimicrobial Studies
Letters in Drug Design & Discovery High Throughput Mutation Screening by Automated Capillary Electrophoresis
Combinatorial Chemistry & High Throughput Screening ELISA-based Protein Arrays: Multiplexed Sandwich Immunoassays
Current Proteomics Propitious Profile of Peppery Piperine
Current Molecular Pharmacology Interactions Between Proteins and Platinum-Containing Anti-Cancer Drugs
Mini-Reviews in Medicinal Chemistry Drug Delivery Nanosystems in Glioblastoma Multiforme Treatment: Current State of the Art
Current Neuropharmacology Pharmacogenomics in Aspirin Intolerance
Current Drug Metabolism Synthesis of Novel Fused Heterocyclic Compounds from 7-amino-[1,2,4]triazino[3,4- b][1,3,4]thiadiazine-8-carbonitrile
Current Organic Synthesis MicroRNAs as Cancer Biomarkers
MicroRNA Glucose Sensors Based on Core@Shell Magnetic Nanomaterials and Their Application in Diabetes Management: A Review
Current Pharmaceutical Design Applications of Metabonomics in Pesticide Toxicology
Current Drug Metabolism Neuropharmacological Mechanisms Underlying the Neuroprotective Effects of Methylphenidate
Current Neuropharmacology Evaluation of Synthetic Cell-Penetrating Peptides, Pro-Rich Peptide and Octaargine Derivatives, as Adenovirus Vector Carrier
Protein & Peptide Letters Toxicology of Tributyltin in Mammalian Animal Models
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued)