Development of New Fibrinolytic Agents

Shigeru      Ueshima; Osamu      Matsuo

doi:10.2174/138161206776056065

Abstract

Since the activation of coagulation system and platelets triggers the thrombosis, the agents possessing anticoagulation or anti-platelet function have been used for the antithrombotic procession actions. However, in the physiological condition, the fibrinolytic system serves as antithrombotic, which removes the thrombus from the circulation. The fibrinolytic system plays an important role in the dissolution of fibrin, which is the main component of thrombus. So that, the balance between the coagulation and fibrinolytic system regulates the formation of thrombus. Now, the new agents that activate the fibrinolytic system have been clinically applied for the thrombolytic therapy. The main factor in fibrinolytic system is the plasmin, which is activated from the plasminogen by the plasminogen activator (PA). The plasminogen activator is mainly used for the thrombolytic therapy. There are two types of PA. One is the non fibrin-specific PA such as streptokinase (SK) and two-chain urokinase-type PA (tcu-PA, urokinase), and another is the fibrin-specific PA such as tissue- type PA (t-PA) and single-chain urokinase-type PA (scu-PA). Recently, some derivatives of t-PA have been developed to obtain the longer half-life than native t-PA and allowed to administrate as the single-bolus. Further, the new fibrin- specific PA such as staphylokinase and bat-PA has been developed. Many attempts have been made to develop the agents that would induce the release of t-PA from endothelial cells. In this review, the development of new fibrinolytic agents is summarized.

Keywords: scu-PA, t-PA, u-PA, Fibrinolysis, mutant t-PA, staphylokinase, bat-PA, endothelial cells