Development of Anisoylated Plasminogen-Streptokinase Activator Complex from the Acyl Enzyme Concept

Fears, Robin

doi:10.1055/s-2007-1002695

Cited by 11 publications

(2 citation statements)

References 36 publications

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“…Anisoylated, lys-plasminogen-streptokinase activator complex (APSAC, or anistreplase) is a complex of human plasminogen and streptokinase, in which the active site of plasminogen has been acylated, rendering the plasminogen inert to activation or inhibition by circulating plasma proteins (24). The result is a longer half-life (92 minutes) but basically the same plasminogen-activating effect as streptokinase (25,26).…”

Section: Anistreplasementioning

confidence: 99%

Thrombolytic Therapy

Baker

2002

Clin Appl Thromb Hemost

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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 the treatment of a variety of arterial and venous thrombotic disorders. The ideal thrombolytic agent has yet to be developed but the desired clinical result of rapid opening of the thrombosed vessel without reocclusion, without activation of systemic fibrinogenolysis, and without a risk of hemorrhage is well defined. Clinical studies clearly demonstrate that the addition of a variety of adjunctive agents to the available thrombolytics enhances benefit without inordinate risk. The addition of intravascular angioplasty and stenting to thrombolysis increases the potential long-term benefit. Newer thrombolytic agents and new protocols for the use of existing therapies offer the promise of saving many who would otherwise succumb to coronary or cerebral arterial thrombosis or to venous thromboembolism.

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Section: Anistreplasementioning

confidence: 99%

Thrombolytic Therapy

Baker

2002

Clin Appl Thromb Hemost

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“…The prolonged serum half-life for APSAC, which is independent of pretreatment anti-SK IgG levels, also enables bolus dosing of APSAC. 19 Theoretically the addition of the acyl group to the SK-plasminogen complex provides thrombus-specific fibrinolysis with decreased risk for a systemic lytic state. However, preliminary clinical experience with APSAC reveals lack of total fibrin specificity because progressive reductions in plasma levels of fibrinogen, plasminogen, and alpha2-antiplasmins have been identified.…”

Section: Streptokinasementioning

confidence: 99%

Thrombolytic Therapy and Modern Vascular Surgery: An Overview

Harris¹,

Porter²

1989

Perspectives in Vascular Surgery and Endovascular Therapy

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a number of clinical situations. In this article we will review the mechanisms of thrombolysis and the clinical use of thrombolytic agents.Thrombolysis is initiated through the activation of the plasma protein plasminogen to the active serine protease, plasmin. Plasminogen activators are naturally occurring proteins that have been identified in injured tissue, blood, urine, endothelial cells, and various body fluids that convert plasminogen into plasmin. The physiologic source of circulating plasminogen activator is believed to be the vascular intima. Thrombolysis occurs as plasmin converts fibrin into soluble degradation products. Though plasmin in high concentration may initiate proteolysis of most plasma proteins, plasmin proteolysis is physiologically specific for the hydrolysis of fibrin. Circulating blood contains a number of inhibitors of fibrinolysis, which appear critical for the maintenance of homeostatic balance.The development of fibrinolytic agents for clinical use began in the mid-1940s following Christensen's description of the fibrinolytic enzyme cascade, which was developed from observations of streptococcal fibrinolysiS.2Because the streptococcal product appeared to be an activator of fibrinolysis rather than a primary fibrinolysin, Christensen suggested the name &dquo;streptokinase&dquo; for this substance. Subsequent investigations identified the binding of plasminogen to fibrin during the formation of thrombus. 3,4 This intercalation is critical to the plasminogen-plasmin zymogen system since fibrin-bound plasminogen is more readily activated than plasma plasminogen4 and the plasmin is formed inside the fibrin clot in an environment shielded from circulating antiplasmins. To mediate lysis of thrombus, plasminogen activators are introduced into the systemic circulation in amounts sufficient to achieve maximal activation of fibrin-bound plasminogen. Some fibrinogen proteolysis invariably occurs during thrombolytic therapy as a result of activation of non-fibrin-bound plasminogen to circulating free plasnun. 5Although originally recommended for the treatment of venous thrombosis and critical pulmonary embolism, thrombolytic therapy has also been used widely in the treatment of acute arterial thromboembolism. However, the major use of thrombolytic therapy has been and will probably continue to be for the treatment of acute myocardial infarction (AMI). Abundant data have shown that, in comparison to conventional therapy, intravenous thrombolytic therapy begun soon after the onset of AMI results in decreased mortality and probable at The University of Auckland Library on June 5, 2016 pvs.sagepub.com Downloaded from

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Cardiovascular Agents

Cervoni¹,

Crandall²,

Chan³

2000

Kirk-Othmer Encyclopedia of Chemical Technology

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The six primary classes of cardiovascular drugs, ie, antiarrhythmic agents, antianginal agents, agents used in the treatment of congestive heart failure, antiatherosclerotic agents, antihypertensive agents, and thrombolytic agents, are reviewed. An overview of the physiology of the cardiovascular system is presented for each class together with the pathology of the system leading to specific cardiovascular disorders. The mechanism(s) of action of the cardiovascular agents are discussed when known, and the principal actions of the cardiovascular agents that contribute to amelioration of the underlying pathology of the cardiovascular disease are reviewed. Side effects and toxicities of the cardiovascular agents are also presented. Drugs clinically in use and some of those drugs under development are discussed. A brief review of the current and projected sales of ethical pharmaceuticals is presented in relation to the sales of cardiovascular agents which is the fastest growing segment of the ethical pharmaceutical market.

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Development of Anisoylated Plasminogen-Streptokinase Activator Complex from the Acyl Enzyme Concept

Cited by 11 publications

References 36 publications

Thrombolytic Therapy

Thrombolytic Therapy

Thrombolytic Therapy and Modern Vascular Surgery: An Overview

Cardiovascular Agents

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