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Overview
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Background
Furegrelate (sodium salt) is a potent inhibitor of thromboxane synthase [1][2].Thromboxane A synthase 1 (platelet, cytochrome P450, family 5, subfamily A) is a cytochrome P450 enzyme that catalyzes the conversion of prostaglandin H2 to thromboxane A2. Thromboxanes play an important role in vasoconstriction and platelet aggregation. Furegrelate (sodium salt), also known as sodium 5-(3'-pyridinylmethyl)benzofuran-2-carboxylate (U-63557A), is a potent, specific and orally available thromboxane synthase inhibitor. U-63557A is a potent inhibitor of the thromboxane synthase in human platelets in vitro, as well as in rhesus monkey platelets ex vivo. U-63557A didn’t inhibit thrombin-stimulated PGI2 biosynthesis in human endothelial cells, the 5-lipoxygenase in human neutrophils, or the cyclooxygenase in a variety of test systems [2]. In rhesus monkeys, U-63557A inhibited the platelet thromboxane synthase by approximately 80% for at least 12 hrs. In anesthetized dogs, U-63557A inhibited the blockage of stenosed coronary arteries caused platelet aggregation. While the protective effects of U-63557A could be reversed by cyclooxygenase inhibitors. U-63557A is a promising compound for the evaluation of the role of thromboxane synthase in a variety of pathophysiological states [2].
[1]. Johnson RA, Nidy EG, Aiken JW, et al. Thromboxane A2 synthase inhibitors. 5-(3-Pyridylmethyl)benzofuran-2-carboxylic acids. J Med Chem. 1986 Aug;29(8):1461-8.
[2]. Gorman RR, Johnson RA, Spilman CH, et al. Inhibition of platelet thromboxane A2 synthase activity by sodium 5-(3'-pyridinylmethyl)benzofuran-2-carboxylate. Prostaglandins. 1983 Aug;26(2):325-42.
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