Plasminogen activators and their potential in therapy.
Plasminogen activators (PAs) are proteases that convert plasminogen to plasmin. Plasmin, in turn, is a protease that can lyse a fibrin clot and, therefore, PAs have a primary role in fibrinolysis. Two PAs, urokinase (UK) and streptokinase (SK), have been available for therapeutic use for years. Unfortunately, both can cause systemic fibrinogenolysis and other side effects which have limited their use. Interest has focused on a different enzyme, tissue plasminogen activator (t-PA), which will cause specific clot lysis without systemic problems. The gene for t-PA has been cloned and many biotechnology firms are preparing to produce t-PA for therapeutic use. The properties and potential for therapy of t-PA are reviewed and compared to new forms of other activators, such as pro-urokinase. How the interactions of PAs and inhibitors may affect the use of PAs is also discussed.
Hollander
I J
IJ
Immunoinflammatory Diseases Research, G. D. Searle Research and Development, Monsanto Life Sciences Research Center, St. Louis, Missouri.
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000188:drug therapy; D010960:Plasminogen Activators / Q000627:therapeutic use*; D013927:Thrombosis / Q000188:drug therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use
D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator