Description
The lipid mediator thromboxane A
2 (TXA
2) plays a key role in platelet aggregation and vascular and bronchial smooth muscle constriction. The actions of TXA
2 are mediated by its specific G protein coupled-receptor, referred to as the TXA
2 receptor or TP. S18886 is an orally active, long-acting antagonist of the TP receptor with an IC
50 value of 16.4 nM. It inhibits TP receptor-mediated vascular contractions, platelet aggregation, and adhesion and infiltration of monocytes/macrophages in various pre-clinical and clinical models of thrombosis or atherosclerosis. S18886 is the active isomer of the potent TP receptor antagonist, S18204. Antagonists of TP receptors have advantages over aspirin as they not only block the effect of TXA
2 on platelets, but also inhibit other ligands such as prostaglandin endoperoxides and isoprostanes.
Uses
Terutroban functions as an anti-platelets therapies for patients with ischemic stroke or transient ischemic attack. Also used in the research process of anti-coagulant drugs in preventing and controlling cerebral stroke.
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].
IC 50
16.4 nm for tp receptor
References
[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.
