Atopaxar (hydrobromide)

Atopaxar is an antagonist of proteinase-activated receptor 1 (PAR1; IC₅₀ = 0.019 µM).¹ It selectively inhibits thrombin- or TRAP-6 amide-induced aggregation of isolated human platelet-rich plasma (IC₅₀s = 0.064 and 0.09 µM, respectively) over ADP-, PAR4-AP-, U-46619-, or collagen-induced aggregation of isolated human platelet-rich plasma at 10 µM. Atopaxar (10 µM) inhibits IL-6-induced phosphorylation of STAT3 in A549 non-small cell lung cancer (NSCLC) cells and transactivation of STAT3 in a reporter assay using A549 cells (IC₅₀ = 5.901 µM).² It reduces granzyme B- and IL-1β-induced cytotoxicity in human neurons derived from induced pluripotent stem cells (iPSCs) when used at a concentration of 1 µM.³ Atopaxar (30 and 100 mg/kg) increases the time to occlusion of the femoral artery but does not affect bleeding time in a guinea pig model of photochemically induced thrombosis.¹

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1. Kogushi, M., Matsuoka, T., Kawata, T., et al. The novel and orally active thrombin receptor antagonist E5555 (Atopaxar) inhibits arterial thrombosis without affecting bleeding time in guinea pigs. Eur. J. Pharmacol. 657(1-3), 131-137 (2011).

2. Sun, J., Du, Y., Zhang, X., et al. Discovery and evaluation of Atopaxar hydrobromide, a novel JAK1 and JAK2 inhibitor, selectively induces apoptosis of cancer cells with constitutively activated STAT3. Invest. New Drugs 38(4), 1003-1011 (2020).

3. Lee, P.R., Johnson, T.P., Gnanapavan, S., et al. Protease-activated receptor-1 activation by granzyme B causes neurotoxicity that is augmented by interleukin-1β. J. Neuroinflammation 14(1), 131 (2017).