2-[2-[[4-(ジフェニルメチル)ピペラジノ]カルボニルメトキシ]アセチルアミノ]-5-クロロ安息香酸ナトリウム

説明TM5275 is an inhibitor of plasminogen activator inhibitor 1 (PAI-1; IC50 = 6.95 μM), a serine-protease inhibitor involved in thrombosis. TM5275 inhibits formation of a complex consisting of tissue plasminogen activator (tPA), PAI-1, and GFP on vascular endothelial cells (VECs) in vitro, prolonging the time that tPA is retained on VECs. It also enhances fibrin clot dissolution and plasminogen accumulation in vitro and has antithrombotic effects in rat models of thrombosis. TM5275 (10 and 50 mg/kg) decreases blood clot weight in an arteriovenous shunt thrombosis model and increases the time to primary occlusion in a ferric chloride-treated carotid artery thrombosis model when used at doses of 1 and 3 mg/kg. In a cynomolgus monkey model of photochemical-induced arterial thrombosis, TM5275 (10 mg/kg) increases the time to primary occlusion. It does not affect platelet activity, activated partial thromboplastin time, prothrombin time, or prolong bleeding time.

使用TM 5275 Sodium Salt is a novel inhibitor of plasminogen activator inhibitor-1 (PAI-1), which provides antithrombitic benefits devoid of bleeding in primates.