Identification of human liver cytochrome P450 enzymes involved in the metabolism of SCH 530348 (Vorapaxar), a potent oral thrombin protease-activated receptor 1 antagonist.

Identification of Human Liver Cytochrome P450 Enzymes Involved in the Metabolism of SCH 530348 (Vorapaxar), a Potent Oral Thrombin (PAR1) Receptor Antagonist

Recent Development in Thrombin Receptor Antagonist as Novel Antithrombotic Agent

Significant progress was achieved in the search of a thrombin receptor antagonist as a novel antithrombotic treatment since the thrombin receptor (protease-activated receptor-1, PAR-1) was cloned 20 years ago. Previous works have shown that it is possible to develop potent thrombin receptor antagonists to compete effectively with the receptor’s internal “tethered” ligand to block platelet activ...

Vorapaxar: The Current Role and Future Directions of a Novel Protease-Activated Receptor Antagonist for Risk Reduction in Atherosclerotic Disease

INTRODUCTION Despite the current standard of care, patients with cardiovascular disease remain at a high risk for recurrent events. Inhibition of thrombin-mediated platelet activation through protease-activated receptor-1 antagonism may provide reductions in atherosclerotic disease beyond those achievable with the current standard of care. OBJECTIVE Our primary objective is to evaluate the cl...

Neuartige Therapie artherothrombotischer Erkrankungen â Ergebnisse präklinischer und klinischer Studien mit SCH 530348, dem ersten thromozytären PAR-1-selektiven Thrombinrezeptor-Antagonisten zur oralen Einnahme

Morbidity and mortality in patients with atherothrombotic disease remain high despite the use of antiplatelet therapy with aspirin and an ADP receptor antagonist. Selective inhibition of the principal protease-activated receptor (PAR)-1 for thrombin, the most potent agonist for platelet activation, represents a promising novel strategy to reduce thrombosis and ischaemic events. SCH 530348, a po...

SCH 602539, a protease-activated receptor-1 antagonist, inhibits thrombosis alone and in combination with cangrelor in a Folts model of arterial thrombosis in cynomolgus monkeys.

OBJECTIVE To determine the antithrombotic effects of SCH 602539, an analog of the selective protease-activated receptor (PAR)-1 antagonist vorapaxar (formerly SCH 530348) currently in advanced clinical development, and the P2Y(12) ADP receptor antagonist cangrelor, alone and in combination. METHODS AND RESULTS Multiple platelet activation pathways contribute to thrombosis. The effects of SCH ...