Description
Vorapaxar is an orally bioavailable competitive antagonist of the proteinase-activated receptor (PAR1; K
i = 8.1 nM), also known as the thrombin receptor. It is selective for PAR1 over other PARs, as well as a number of GPCRs, ion channels, and receptors. It inhibits platelet aggregation induced by thrombin and haTRAP (IC
50s = 47 and 25 nM, respectively). Vorapaxar (0.1 mg/kg, i.v.) completely inhibits platelet aggregation in cynomolgus monkeys
ex vivo. Formulations containing vorapaxar are used in the prevention of thrombotic cardiovascular events.
Definition
ChEBI: A carbamate ester that is the ethyl ester of [(1R,3aR,4aR,6R,8aR,9S,9aS)-9-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]ethyny
}-1-methyl-3-oxododecahydronaphtho[2,3-c]furan-6-yl]carbamic acid. A protease-activated receptor-1 antagonist used (as its sulfate salt) for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction
MI) or with peripheral arterial disease. It has been shown to reduce the rate of a combined endpoint of cardiovascular death, MI, stroke and urgent coronary revascularisation.
References
[1]. chackalamannil s & xia, y. thrombin receptor (par-1) antagonists as novel antithrombotic agents. expert opinion on therapeutic patents, 2006.16:493-505.
[2]. chackalamannil s, wang y, greenlee w j et al. 2008. discovery of a novel, orally active himbacine-based thrombin receptor antagonist (sch 530348) with potent antiplatelet activity. j med chem, 2008,51: 3061-3064.
