Vorapaxar is an orally bioavailable competitive antagonist of the proteinase-activated receptor (PAR1; Ki = 8.1 nM), also known as the thrombin receptor.1 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 (IC50s = 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.
1.Chackalamannil, S., Wang, Y., Greenlee, W.J., et al.Discovery of a novel, orally active himbacine-based thrombin receptor antagonist (SCH 530348) with potent antiplatelet activityJ. Med. Chem.51(110)3061-3064(2008)