Background:

Ozagrel(OKY-046) is an antiplatelet agent working as a thromboxane A2 synthesis inhibitor.Target: Thromboxane A2 SynthaseOzagrel was selected as the best compound of highly selective inhibitors of TXA2 synthase. The inhibition of TXA2 synthase by ozagrel was more effective on human and rabbit enzymes than those of other species. Ozagrel increased 6-keto-PGF1 alpha, one of stable metabolites of PGI2, in various isolated cells and tissues perhaps via accumulated PG endoperoxides resulted by the inhibition of TXA2 synthase [1]. Ozagrel was estimated to be a reversible mixed-type inhibitor of diphenolase activity with the constants (K (S1), K (S2), K (i1), and K (i2)) determined to be 2.21, 3.89, 0.454, and 0.799 mM, repectively [2]. Infusion of OKY-046 significantly inhibited pulmonary thromboxane B2 delivery, attenuated the early increase in pulmonary vascular resistance, and blocked the increase in systemic vascular resistance. In addition, OKY-046 blunted and delayed the decrease in cardiac output and maintained end-systolic pressure-diameter relation, +dp/dt, and lung lymph flow at baseline values [3].

参考文献:
[1]. Nakazawa, M., et al., [Research and development of ozagrel, a highly selective inhibitor of TXA2 synthase]. Yakugaku Zasshi, 1994. 114(12): p. 911-33.
[2]. Li, S.B., et al., In vitro effect of ozagrel on mushroom tyrosinase. Protein J, 2009. 28(3-4): p. 182-8.
[3]. Westphal, M., et al., Selective thromboxane A2 synthase inhibition by OKY-046 prevents cardiopulmonary dysfunction after ovine smoke inhalation injury. Anesthesiology, 2005. 102(5): p. 954-61.