Atopaxar (hydrobromide)

Atopaxar (E5555) hydrobromide is a potent, orally active, selective and reversible thrombin receptor protease-activated receptor-1 (PAR-1) antagonist. Atopaxar hydrobromide is the inhibitor for Janus kinase 1 (JAK1) and JAK2, which inhibits the JAK-STAT with EC₅₀ of 5.90 μM in A549. Atopaxar hydrobromide inhibits the cell viability of A549 (IC₅₀=7.02 μM), arrests the cell cycle at G1 phase and induces apoptosis. Atopaxar hydrobromide exhibits antiplatelet and antitumor activities. Atopaxar hydrobromide can be used for the research of atherothrombotic disease^[1][2][3]. IC50 & Target:PAR-1^[1] In Vitro:Atopaxar hydrobromide (0.0001-10 μM; 1h) inhibits haTRAP (high-affinity thrombin receptor activating peptide) binding to PAR-1 on human platelet membranes in a concentration-dependent manner, with an IC₅₀ of 0.019 μM^[2].
Atopaxar hydrobromide shows potent inhibitory effects on human platelet aggregation induced by thrombin and TRAP with IC₅₀s of 0.064 and 0.031 μM, respectively, but has no effect on platelet aggregation induced by either ADP or collagen^[2].
Atopaxar hydrobromide shows potent and selective inhibitory effects on guinea pig platelet aggregation induced by thrombin and TRAP with IC₅₀s of 0.13 and 0.097 μM, respectively^[2]. In Vivo:Atopaxar (30-100 mg/kg; p.o.) hydrobromide causes a dose-dependent prolongation of the time to occlusion of the femoral artery in photochemically-induced thrombosis (PIT) guinea pigs model^[2].
Atopaxar hydrobromide does not prolong bleeding time in guinea pigs at the highest tested dosage of 1000 mg/kg^[2].