TM5275

TM5275 is an inhibitor of plasminogen activator inhibitor 1 (PAI-1; IC₅₀ = 6.95 µM), a serine-protease inhibitor involved in thrombosis.¹ 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.² It also enhances fibrin clot dissolution and plasminogen accumulation in vitro and has antithrombotic effects in rat models of thrombosis.¹ 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.

WARNING This product is not for human or veterinary use.

1. Izuhara, Y., Yamaoka, N., Kodama, H., et al. A novel inhibitor of plasminogen activator inhibitor-1 provides antithrombotic benefits devoid of bleeding effect in nonhuman primates. J. Cereb. Blood Flow Metab. 30(5), 904-912 (2010).

2. Yasui, H., Suzuki, Y., Sano, H., et al. TM5275 prolongs secreted tissue plasminogen activator retention and enhances fibrinolysis on vascular endothelial cells. Thromb. Res. 132(1), 100-105 (2013).