The search for the ideal thrombolytic agent.
Since streptokinase and urokinase became available for clinical use, numerous attempts have been made to improve these useful thrombolytic agents. To decrease its antigenicity, streptokinase has been fragmented or coupled to human plasminogen or polyethylene glycols. With a plasmin B chain-streptokinase complex a more potent agent was obtained. To prolong their half-life, streptokinase and urokinase were immobilized with water-soluble carriers. Coupling urokinase with fibrin-specific antibodies increases its thrombolytic efficacy, at least in vitro. The only thrombolytic agents with a relative fibrin specificity available for clinical purposes are tissue-type plasminogen activator and single chain urokinase-type plasminogen activator. Mutants and hybrids of these molecules are being constructed and may further improve their fibrin specificity and therapeutic potential.
D004338:Drug Combinations / Q000494:pharmacology / Q000627:therapeutic use; D004800:Enzymes, Immobilized / Q000494:pharmacology / Q000627:therapeutic use; D005341:Fibrinolysin / Q000494:pharmacology / Q000627:therapeutic use; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009154:Mutation; D010958:Plasminogen / Q000494:pharmacology / Q000627:therapeutic use; D010960:Plasminogen Activators / Q000494:pharmacology / Q000627:therapeutic use; D011092:Polyethylene Glycols; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013300:Streptokinase / Q000494:pharmacology / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000494:pharmacology / Q000627:therapeutic use; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology / Q000627:therapeutic use
D004338:Drug Combinations; D004800:Enzymes, Immobilized; D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; C049423:streptokinase-plasminogen complex; D011092:Polyethylene Glycols; D010958:Plasminogen; D013300:Streptokinase; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator