Abstract
Various oral platelet GPIIb / IIIa receptor antagonists have undergone clinical investigations, but to date without success. Various factors have been proposed to explain their failure such as low affinity for the receptor, large peak / trough ratio, low bioavailability, partial agonist activity and pro-aggregatory effect. Efforts to discover a truly effective, safe, oral antagonist led to the discovery of UR-3216 (Fig. 1). The active form of UR-3216, UR-2922, possessed a high affinity for the human platelet receptor (Kd < 1 nM) with a slow dissociation rate (koff = 90 min) in vitro. UR-2922 induced no ligandinduced binding sites (LIBS) expression or prothrombotic activity in human platelets, distinctly different from orbofiban and other small molecule antagonists. To date, UR-2922 is the only high affinity GPIIb / IIIa antagonist without LIBS expression. In vivo characteristics of UR-3216 showed prolonged duration of efficacy ( > 24 h) with its favorable pharmacokinetic profile, superior to all the other oral GPIIb / IIIa antagonists. UR-3216 showed high bioavailability, rapid bioconversion to the active form and biliary excretion. UR-3216 is a novel, orally active GPIIb / IIIa antagonist of a new generation, which has substantially improved the crucial compounding factors and will be useful for the treatment of cardiovascular diseases.
Keywords: ur-3216, antiplatelet drug, thrombosis
Current Pharmaceutical Design
Title: UR-3216: A New Generation Oral Platelet GPIIb / IIIa Antagonist
Volume: 10 Issue: 14
Author(s): Yasuhiro Aga, Kosuke Baba, Susan Tam, Takayuki Nakanishi, Kenji Yoneda, Jun-ichiro Kita and Hitoshi Ueno
Affiliation:
Keywords: ur-3216, antiplatelet drug, thrombosis
Abstract: Various oral platelet GPIIb / IIIa receptor antagonists have undergone clinical investigations, but to date without success. Various factors have been proposed to explain their failure such as low affinity for the receptor, large peak / trough ratio, low bioavailability, partial agonist activity and pro-aggregatory effect. Efforts to discover a truly effective, safe, oral antagonist led to the discovery of UR-3216 (Fig. 1). The active form of UR-3216, UR-2922, possessed a high affinity for the human platelet receptor (Kd < 1 nM) with a slow dissociation rate (koff = 90 min) in vitro. UR-2922 induced no ligandinduced binding sites (LIBS) expression or prothrombotic activity in human platelets, distinctly different from orbofiban and other small molecule antagonists. To date, UR-2922 is the only high affinity GPIIb / IIIa antagonist without LIBS expression. In vivo characteristics of UR-3216 showed prolonged duration of efficacy ( > 24 h) with its favorable pharmacokinetic profile, superior to all the other oral GPIIb / IIIa antagonists. UR-3216 showed high bioavailability, rapid bioconversion to the active form and biliary excretion. UR-3216 is a novel, orally active GPIIb / IIIa antagonist of a new generation, which has substantially improved the crucial compounding factors and will be useful for the treatment of cardiovascular diseases.
Export Options
About this article
Cite this article as:
Aga Yasuhiro, Baba Kosuke, Tam Susan, Nakanishi Takayuki, Yoneda Kenji, Kita Jun-ichiro and Ueno Hitoshi, UR-3216: A New Generation Oral Platelet GPIIb / IIIa Antagonist, Current Pharmaceutical Design 2004; 10 (14) . https://dx.doi.org/10.2174/1381612043384592
DOI https://dx.doi.org/10.2174/1381612043384592 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
![](/images/wayfinder.jpg)
- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
Isoform Selective Voltage-Gated Sodium Channel Modulators and the Therapy of Pain
Current Medicinal Chemistry Neuropeptide/Receptor Expression and Plasticity in Micturition Pathways
Current Pharmaceutical Design Genetics of Atrial Fibrilation: In Search of Novel Therapeutic Targets
Cardiovascular & Hematological Disorders-Drug Targets Drugs for AIDS
Mini-Reviews in Medicinal Chemistry Meet the Editorial Board
Current Alzheimer Research Lipid Metabolism in Patients with End-Stage Renal Disease: A Five Year Follow-up Study
Current Vascular Pharmacology Application of Multivariate Linear and Nonlinear Calibration and Classification Methods in Drug Design
Combinatorial Chemistry & High Throughput Screening Highly Active Antiretroviral Therapy-Induced Liver Injury
Current Drug Safety Fas Ligand Gene Therapy for Vascular Intimal Hyperplasia
Current Gene Therapy Anti-apoptotic Serpins as Therapeutics in Cardiovascular Diseases
Cardiovascular & Hematological Disorders-Drug Targets Inducible Nitric Oxide Synthase as a Possible Target in Hypertension
Current Drug Targets Editorial [Hot topic: Transportalopathy and Vascular Cell Dysfunction (Guest Editor: Luis Sobrevia)]
Current Vascular Pharmacology Editorial [Hot Topic:Continuous Glucose Monitoring Systems: Toys or Tools (Guest Editor: Christophe De Block)]
Current Diabetes Reviews A Tai Chi Chuan Training Model to Improve Balance Control in Older Adults
Current Aging Science The Epidemiology of Sleep Disordered Breathing and Hypertension in Various Populations
Current Hypertension Reviews <i>In Vivo/Ex Vivo</i> EPR Investigation of the Brain Redox Status and Blood-Brain Barrier Integrity in the 5xFAD Mouse Model of Alzheimer's Disease
Current Alzheimer Research Adult Stem Cell Treatment for Central Nervous System Injury
Current Tissue Engineering (Discontinued) Artificial Blood: A Futuristic Dimension of Modern Day Transfusion Sciences
Cardiovascular & Hematological Agents in Medicinal Chemistry The Intermediate Enzymes of Isoprenoid Metabolism as Anticancer Targets
Anti-Cancer Agents in Medicinal Chemistry Meet Our Editorial Board Member
Current Cardiology Reviews