Protease-activated receptor-1 antagonists: focus on SCH 530348.

Abstract

Currently available antiplatelet agents have shown improved short- and long-term clinical outcomes but are associated with increased bleeding risk, and the rates of recurrent ischemic events still remain high. Selective inhibition of protease-activated receptor-1 for thrombin represents a potential novel strategy to reduce ischemic events without increasing the risk of bleeding. Two protease-activated receptor-1 antagonists are currently being evaluated in clinical trials: SCH 530348 and E5555. Results of phase II trials have shown that SCH 530348, when added to standard antiplatelet therapy, was well tolerated and not associated with increased bleeding risk. Two large-scale phase III trials assessing the efficacy of SCH 530348 in addition to the standard of care are currently ongoing. This review provides an outline of the current status of understanding on platelet thrombin-receptor antagonist SCH 530348, focusing on its pharmacologic properties and clinical development.

• Authors: Jaya Prakash Sugunaraj, Vimal Mehta, Ankur Kalra, Rishi Sukhija, Chandrasekar Palaniswamy
• Journal: American journal of therapeutics (Am J Ther) Vol. 19 Issue 6 Pg. 465-9 (Nov 2012) ISSN: 1536-3686 [Electronic] United States
• PMID: 21248619 (Publication Type: Journal Article, Review)

Chemical References

• Lactones
• Platelet Aggregation Inhibitors
• Pyridines
• Receptor, PAR-1
• Receptors, Thrombin
• vorapaxar

Topics

• Clinical Trials, Phase II as Topic
• Clinical Trials, Phase III as Topic
• Drug Design
• Hemorrhage (chemically induced)
• Humans
• Lactones (adverse effects, pharmacology)
• Platelet Aggregation Inhibitors (adverse effects, pharmacology)
• Pyridines (adverse effects, pharmacology)
• Receptor, PAR-1 (antagonists & inhibitors)
• Receptors, Thrombin (antagonists & inhibitors)