Development of New Fibrinolytic Agents

Ueshima, Shigeru; Matsuo, Osamu
March 2006
Current Pharmaceutical Design;Mar2006, Vol. 12 Issue 7, p849
Academic Journal
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.


Related Articles

  • Fibrinolysis at the Fluid-Solid Interface of Thrombi. Kolev, K.; Longstaff, C.; Machovich, R. // Current Medicinal Chemistry - Cardiovascular & Hematological Age;Oct2005, Vol. 3 Issue 4, p341 

    Thrombolysis is conventionally regarded as dissolution of the fibrin matrix of thrombi by plasmin, a protease generated by plasminogen activators from its inactive precursor, plasminogen. Typically plasminogen activation occurs on the surface of the clot, where fibrin behaves as a cofactor in...

  • The Biochemical and Physical Process of Fibrinolysis and Effects of Clot Structure and Stability on the Lysis Rate. Weisel, J. W.; Litvinov, R. I. // Cardiovascular & Hematological Agents in Medicinal Chemistry;2008, Vol. 6 Issue 3, p161 

    The effectiveness of fibrinolysis results from the combination of regulated enzymatic activity and the physical properties of the fibrin scaffold. Physiologically, clots or thrombi are dissolved from within via internal lysis. In contrast, with therapeutic thrombolysis, lytic agents are...

  • Lumbrokinase -- A Potent and Stable Fibrin--Specific Plasminogen Activator. Verma, Mahendra Kumar; Pulicherla, K. K. // International Journal of Bio-Science & Bio-Technology;Jun2011, Vol. 3 Issue 2, p57 

    Cardio and cerebrocascular disorders lead to about 26 million deaths every year around the world. Cardio and cerebrovaccular disorders have not only high mortality rate across the globe but also leading to subsequent complication such as thrombolysis could favorably influence the outcome of such...

  • Evaluation of Two Recombinant Plasminogen Activators in Massive Pulmonary Embolism Model and Potato Carboxypeptidase Inhibitor (PCI) role in Inhibition of Thrombin Activatable Fibrinolysis Inhibitor TAFIa in Lungs. Konecny, Filip // Recent Patents on Endocrine, Metabolic & Immune Drug Discovery;Jan2008, Vol. 2 Issue 1, p45 

    Massive pulmonary embolism (MPE) is characterized by high mortality. Two thirds of patients die within the first hour of MPE presentation. Significantly lower mortality could be achieved by using the optimal therapeutic dose of plasminogen activators (PAc's). It was expected that Retavase,...

  • Thrombolytic Therapy. Baker Jr., William F. // Clinical & Applied Thrombosis/Hemostasis;Oct2002, Vol. 8 Issue 4, p291 

    The therapeutic use of thrombolytic agents is the natural result of the increasing understanding of the pathophysiologic mechanisms underlying normal and deranged thrombosis and fibrinolysis. Plasminogen activators capable of increasing the production of plasmin exhibit considerable efficacy in...

  • CORONARY ARTERIAL AND OTHER INTRAVASCULAR THROMBOSES TREATED WITH FIBRINOLYSIN. Mazel, M. S.; Bolton, Houck E.; Stern, Joel R.; Riera, Rogelio; Cabral, Hector // Angiology;Feb1963, Vol. 14 Issue 2, p88 

    Investigates the efficacy of fibrinolytic agents for the treatment of intravascular thromboses. Accomplishment of cerebral embolization by cannulation of the carotid artery; Doubts on the actual amount of fibrinolysin which the brain can tolerate by perfusion of a carotid artery; Safety profile...

  • Fibrin Binding and the Regulation of Plasminogen Activators during Thrombolytic Therapy. Longstaff, C.; Williams, S.; Thelwell, C. // Cardiovascular & Hematological Agents in Medicinal Chemistry;2008, Vol. 6 Issue 3, p212 

    First generation thrombolytics (streptokinase and urokinase) had no fibrin binding capabilities and caused systemic plasminogen activation with concomitant destruction of haemostatic proteins. A primary driving force behind the development of the second generation plasminogen activator tissue...

  • A Pilot Study into the Removal of Blood Clots using tPA Delivered Locally through the 'GP' Mechanical Thrombectomy Device. Pearce, Gillian; Perkinson, Neil; Brooker, Lee; Wong, Julian // International Journal of Technology, Knowledge & Society;2011, Vol. 7 Issue 1, p107 

    We present data concerning the use of tPA with our recently invented thrombus aspiration device as a means of extracting blood clots in in-vitro experiments. We also remove the blood clots using the aspiration device alone. Our esults are compared. Background There are approximately 130,000...

  • Simultaneous Measurement of All Thrombosis Parameters from Native Human Blood: Usefulness in Monitoring Efficacy and Complications of Thrombolytic Therapy. Kovacs, Iren B.; Path, F. R. C.; Görög, Peter; Path, M.R.C. // Angiology;Oct1990, Vol. 41 Issue 10, p829 

    The sequelae of thrombus formation, both by shear forces and by collagen fiber, the subsequent coagulation, and the dislodgement of thrombi (thrombolysis) were measured from a small volume of nonanticoagulated blood sample, by a new instrument. Addition of streptokinase (SK) or tissue-type...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics