Abstract
Venous thromboembolic disease, including deep vein thrombosis and pulmonary embolism, is a cause of significant mortality and morbidity. For several decades, anticoagulant options for the treatment and prevention of thrombosis have been limited mainly to agents such as unfractionated heparin and oral vitamin K antagonists such as warfarin. Although these therapies have proven benefits, they also have important limitations that result in their underuse in routine clinical practice. A variety of novel anticoagulants with improved pharmacologic and clinical profiles are in development, offering benefits over traditional therapies. Specifically, progress has been made in the development of small molecule Factor Xa inhibitors and thrombin inhibitors. The most advanced drugs reviewed include DPC-423, DPC- 602, razaxaban, GSKs 813893, Portolas Xa inhibitors (formerly Millennium), otamixaban, DU-176b, KFA-1982, BAY- 59-7939, DX-9065a, YM-150, LY-517717, Exanta, 3DPs thrombin inhibitors, SSR-182289, LB-30057, LB-30870, BIBR-1048 and Mercks thrombin inhibitors. With their potentially consistent and predictable pharmacological profile, oral formulation, and decreased need for coagulation monitoring, these new agents will likely increase the use and duration of anticoagulation treatment in thromboembolic disorders and reduce the burden associated with long-term management.
Keywords: Venous thromboembolism, Anticoagulant Agent, DPC-423, Razaxaban, antithrombotic, LY-517717
Current Topics in Medicinal Chemistry
Title: Small Molecule Coagulation Cascade Inhibitors in the Clinic
Volume: 5 Issue: 16
Author(s): Eddine Saiah and Chris Soares
Affiliation:
Keywords: Venous thromboembolism, Anticoagulant Agent, DPC-423, Razaxaban, antithrombotic, LY-517717
Abstract: Venous thromboembolic disease, including deep vein thrombosis and pulmonary embolism, is a cause of significant mortality and morbidity. For several decades, anticoagulant options for the treatment and prevention of thrombosis have been limited mainly to agents such as unfractionated heparin and oral vitamin K antagonists such as warfarin. Although these therapies have proven benefits, they also have important limitations that result in their underuse in routine clinical practice. A variety of novel anticoagulants with improved pharmacologic and clinical profiles are in development, offering benefits over traditional therapies. Specifically, progress has been made in the development of small molecule Factor Xa inhibitors and thrombin inhibitors. The most advanced drugs reviewed include DPC-423, DPC- 602, razaxaban, GSKs 813893, Portolas Xa inhibitors (formerly Millennium), otamixaban, DU-176b, KFA-1982, BAY- 59-7939, DX-9065a, YM-150, LY-517717, Exanta, 3DPs thrombin inhibitors, SSR-182289, LB-30057, LB-30870, BIBR-1048 and Mercks thrombin inhibitors. With their potentially consistent and predictable pharmacological profile, oral formulation, and decreased need for coagulation monitoring, these new agents will likely increase the use and duration of anticoagulation treatment in thromboembolic disorders and reduce the burden associated with long-term management.
Export Options
About this article
Cite this article as:
Saiah Eddine and Soares Chris, Small Molecule Coagulation Cascade Inhibitors in the Clinic, Current Topics in Medicinal Chemistry 2005; 5 (16) . https://dx.doi.org/10.2174/156802605775009702
DOI https://dx.doi.org/10.2174/156802605775009702 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Flavonoids in Atherosclerosis: An Overview of Their Mechanisms of Action
Current Medicinal Chemistry Fondaparinux for the Prevention or Treatment of Venous ThromboEmbolism Related to Lower Limb Trauma: Evidence Today
Current Vascular Pharmacology Development of Trypsin-Like Serine Protease Inhibitors as Therapeutic Agents: Opportunities, Challenges, and their Unique Structure-Based Rationales
Current Topics in Medicinal Chemistry Biomarkers Associated with Bleeding Risk in the Setting of Atrial Fibrillation
Current Medicinal Chemistry Idarucizumab: Clinical Role of a Novel Reversal Agent for Dabigatran
Cardiovascular & Hematological Disorders-Drug Targets New Oral Anticoagulation after Heart Valve Replacement
Cardiovascular & Hematological Disorders-Drug Targets Cardiovascular Pharmacogenomics
Current Pharmacogenomics and Personalized Medicine Genetic Variability of Matrix Metalloproteinase Genes in Cardiovascular Disease
Current Topics in Medicinal Chemistry Elevated Levels of Soluble Fibrin in Patients with Thrombosis or a Pre- Thrombotic State
Vascular Disease Prevention (Discontinued) Apixaban - Metabolism, Pharmacologic Properties and Drug Interactions
Current Drug Metabolism The Emerging Role of microRNA in Stroke
Current Topics in Medicinal Chemistry Arterial Duct Stenting in Congenital Heart Disease with Duct-Dependent Pulmonary Circulation
Current Pediatric Reviews Mathematical Models of Blood Coagulation and Platelet Adhesion: Clinical Applications
Current Pharmaceutical Design Deep Venous Thrombosis Associated with Thalidomide use in a Case of Steroid Dependent Erythema Nodosum Leprosum-a Management Conundrum
Current Drug Safety Gene Therapy for Cardiovascular Diseases
Current Pharmaceutical Design Effect of Cardioembolic Etiology on Intravenous Thrombolysis Efficacy for Acute Ischemic Stroke
Current Neurovascular Research Current Therapeutic Strategies and Future Perspectives for the Prevention of Arterial Thromboembolism: Focus on Atrial Fibrillation
Current Pharmaceutical Design Pathophysiology of Coronary Thrombus Formation and Adverse Consequences of Thrombus During PCI
Current Cardiology Reviews Microparticles in Health and Disease: Small Mediators, Large Role?
Current Vascular Pharmacology Ophthalmological and Otological Manifestations in the Antiphospholipid Syndrome
Current Rheumatology Reviews