SCH79797 dihydrochloride is a highly potent and selective nonpeptide protease activated receptor 1 (PAR1) antagonist. It inhibits the binding of a high-affinity thrombin receptor-activating peptide to PAR1 with an IC50 of 70 nM and a Ki of 35 nM. SCH79797 dihydrochloride also inhibits thrombin-induced platelet aggregation with an IC50 of 3 μM. Moreover, it has antiproliferative and pro-apoptotic effects, and limits myocardial ischemia/reperfusion injury in rat hearts. Additionally, SCH79797 dihydrochloride potently prevents PAR1 activation in vascular smooth muscle cells, endothelial cells, and astrocytes[1][2][3][4].
体内研究
SCH79797 (2.5-250 μg/kg; intravenous injection; male Sprague Dawley rats) immediately before or during ischemia reduces myocardial necrosis following I/R in the intact rat heart in two rat models of myocardial ischemia/reperfusion (I/R) injury. This response is dose-dependent, with the optimal dose being 25 μg/kg[4].
体外研究
SCH79797 inhibits high-affinity thrombin receptor-activating peptide ([3H]haTRAP) binding in a competitive manner. It also inhibits α-thrombin- and haTRAP-induced aggregation of human platelets, while not inhibiting human platelet aggregation induced by other agonists. Furthermore, SCH79797 effectively inhibits the transient increases in cytosolic free Ca2+ concentration ([Ca2+]i) in hCASMC induced by thrombin. Additionally, it completely inhibits Thrombin- and TK-stimulated [3H]thymidine incorporation[1].
SCH79797 is capable of interfering with the growth of several human and mouse cell lines in a concentration-dependent manner. It exhibits ED50 values of 75 nM, 81 nM, and 116 nM for growth inhibition in NIH 3T3, HEK 293, and A375 cells, respectively. In NIH 3T3 cells, SCH79797 inhibits serum-stimulated activation of p44/p42 mitogen-activated protein kinases (MAPK) at low concentrations and induces apoptosis at higher concentrations[2].
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