Abstract
Thrombin is a key enzyme of blood coagulation system which has multiple functions including pro- and anticoagulant, platelet aggregating and inflammatory activities. Unsurprisingly, this enzyme has been a target for anticoagulant drug development for decades. Among the most interesting direct thrombin inhibitors with intravenous administration route are the following ones: 1) hirudins, proteins with bivalent binding mode to the thrombin, 2) bivalirudin, the peptide with bivalent binding mode to the thrombin, 3) argatroban, the chemical that binds to the thrombin active site, and 4) G-quadruplex DNA aptamers, structured oligonucleotides with an affinity to protein-binding site of the thrombin. Efficiency of all these inhibitors has been studied in vivo in preclinical and clinical trials, as well as in vitro with various tests, allowing to compare them thoroughly.
In the review three levels of comparison were used to highlight the features of each inhibitor: 1) thrombin inhibition constants as a characteristic of inhibitor potency in simple enzymatic system; 2) inhibition of fibrin fiber formation and thrombin generation in coagulation cascade as a characteristic of anticoagulant potency in human blood plasma; and 3) therapeutic doses used and therapeutic profiles obtained after intravenous administration into animals and humans. The data clearly demonstrate weak and strong aspects of thrombin binding aptamers providing a solid background for further novel anticoagulant development.
Keywords: Anticoagulant, Aptamer, Coagulation, Inhibitor, Thrombin, Thrombin generation test.
Current Medicinal Chemistry
Title:G-Quadruplex Aptamers to Human Thrombin Versus Other Direct Thrombin Inhibitors: The Focus on Mechanism of Action and Drug Efficiency as Anticoagulants
Volume: 23 Issue: 21
Author(s): Elena Zavyalova, Nikita Ustinov, Andrey Golovin, Galina Pavlova and Alexey Kopylov
Affiliation:
Keywords: Anticoagulant, Aptamer, Coagulation, Inhibitor, Thrombin, Thrombin generation test.
Abstract: Thrombin is a key enzyme of blood coagulation system which has multiple functions including pro- and anticoagulant, platelet aggregating and inflammatory activities. Unsurprisingly, this enzyme has been a target for anticoagulant drug development for decades. Among the most interesting direct thrombin inhibitors with intravenous administration route are the following ones: 1) hirudins, proteins with bivalent binding mode to the thrombin, 2) bivalirudin, the peptide with bivalent binding mode to the thrombin, 3) argatroban, the chemical that binds to the thrombin active site, and 4) G-quadruplex DNA aptamers, structured oligonucleotides with an affinity to protein-binding site of the thrombin. Efficiency of all these inhibitors has been studied in vivo in preclinical and clinical trials, as well as in vitro with various tests, allowing to compare them thoroughly.
In the review three levels of comparison were used to highlight the features of each inhibitor: 1) thrombin inhibition constants as a characteristic of inhibitor potency in simple enzymatic system; 2) inhibition of fibrin fiber formation and thrombin generation in coagulation cascade as a characteristic of anticoagulant potency in human blood plasma; and 3) therapeutic doses used and therapeutic profiles obtained after intravenous administration into animals and humans. The data clearly demonstrate weak and strong aspects of thrombin binding aptamers providing a solid background for further novel anticoagulant development.
Export Options
About this article
Cite this article as:
Zavyalova Elena, Ustinov Nikita, Golovin Andrey, Pavlova Galina and Kopylov Alexey, G-Quadruplex Aptamers to Human Thrombin Versus Other Direct Thrombin Inhibitors: The Focus on Mechanism of Action and Drug Efficiency as Anticoagulants, Current Medicinal Chemistry 2016; 23 (21) . https://dx.doi.org/10.2174/0929867323666160517120126
DOI https://dx.doi.org/10.2174/0929867323666160517120126 |
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
-
Simulated Microgravity Based Stem Cell Cultures Enhance Their Utility for Cell-Based Therapy
Current Biotechnology Opioid-induced Cardioprotection
Current Pharmaceutical Design Leaf Aqueous Extract of Argania spiniosa Exhibits Antihyperglycemic Effect in Diabetic Rats
Cardiovascular & Hematological Agents in Medicinal Chemistry The Contribution of Cerebral Vascular Neuropathology to Mild Stage of Alzheimer’s Dementia Using the NACC Database
Current Alzheimer Research The Effects of Caffeine on the Cholinergic System
Mini-Reviews in Medicinal Chemistry Cerebral Arachidonate Cascade in Dementia: Alzheimers Disease and Vascular Dementia
Current Neuropharmacology The Importance of Stereochemistry on the Actions of Vitamin D
Current Topics in Medicinal Chemistry Development of Radiolabeled Compounds for Myocardial Perfusion Imaging
Current Pharmaceutical Design Can Decision Making Research Provide a Better Understanding of Chemical and Behavioral Addictions?
Current Drug Abuse Reviews Pleiotropic Effects of Drugs Inhibiting the Renin-Angiotensin-Aldosterone System
Current Pharmaceutical Design Carbohydrates in Therapeutics
Cardiovascular & Hematological Agents in Medicinal Chemistry Arterial Duct Stenting in Congenital Heart Disease with Duct-Dependent Pulmonary Circulation
Current Pediatric Reviews Editorial from Guest Editors [Hot Topic: Children with Congenital Heart Disease (Guest Editors: Kris De Boeck and Tony Reybrouck)]
Current Respiratory Medicine Reviews Regulation of Smooth Muscle Myosin Light Chain Phosphatase by Multisite Phosphorylation of the Myosin Targeting Subunit, MYPT1
Cardiovascular & Hematological Disorders-Drug Targets Immune System Modulates the Function of Adult Neural Stem Cells
Current Immunology Reviews (Discontinued) Acute Toxicological and Histopathological Elucidation of <i>Rheum emodi</i> Rhizome Extract to Demonstrate Antidiabetic Activity in Alloxan-induced Diabetic Rats
Current Bioactive Compounds Plant-food-derived Bioactives in Managing Hypertension: From Current Findings to Upcoming Effective Pharmacotherapies
Current Topics in Medicinal Chemistry The Role of Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging in Drug Development for Ischemic Stroke: From Laboratory to Clinics
Current Vascular Pharmacology Effective Strategies for Diagnosis of Systemic Inflammatory Response Syndrome (SIRS) due to Bacterial Infection in Surgical Patients
Infectious Disorders - Drug Targets Actigraphy for Assessing Light Effects on Sleep and Circadian Activity Rhythm in Alzheimer's Dementia: A Narrative Review
Current Alzheimer Research