A TP receptor antagonist
IC50: 16.4 nM for TP receptor
S18886 is a potent thromboxane A2 (TP) inhibitor.
The lipid mediator thromboxane A2 (TXA2) plays a critical role in platelet aggregation and vascular and bronchial smooth muscle constriction. The actions of TXA2 are mediated via the specific G protein coupled-receptor, TXA2 receptor (TP).
In vitro: S18886 was identified as the active isomer of the potent TP receptor antagonist S18204. S18886 was also found to be a selective antagonist of thromboxaneprostaglandin receptors in platelets and in the vessel wall [1].
In vivo: In a previous animal study, it was found that S18886 treatment could reduce the portal pressure in both animal models without producing significant changes in portal blood flow, indicating a reduction in hepatic vascular resistance. S18886 could not significantly change arterial pressure in CCl4 -cirrhotic rats but could significantly decrease it in BDL-cirrhotic rats [2].
Clinical trial: A previoius trial aiming to evaluate S18886 versus aspirin in patients with cerebral ischaemic events showed similar rates of the primary endpoint with S18886 and aspirin, without safety advantages for S18886 [3].
参考文献:
[1] Cimetière B, Dubuffet T, Landras C, Descombes JJ, Simonet S, Verbeuren TJ, Lavielle G.? New tetrahydronaphthalene derivatives as combined thromboxane receptor antagonists and thromboxane synthase inhibitors. Bioorg Med Chem Lett. 1998 Jun 2;8(11):1381-6.
[2] Rosado E, Rodríguez-Vilarrupla A, Gracia-Sancho J, Tripathi D, García-Calderó H, Bosch J, García-Pagán JC.? Terutroban, a TP-receptor antagonist, reduces portal pressure in cirrhotic rats. Hepatology. 2013 Oct;58(4):1424-35.
[3] Bousser MG, Amarenco P, Chamorro A, Fisher M, Ford I, Fox KM, Hennerici MG, Mattle HP, Rothwell PM, de Cordoüe A, Fratacci MD; PERFORM Study Investigators.?Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial. Lancet. 2011 Jun 11;377(9782):2013-22.
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