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Matches in SemOpenAlex for { <https://semopenalex.org/work/W2056549607> ?p ?o ?g. }

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• W2056549607 abstract "Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of tissue plasminogen activator (tPA) and is elevated in diseases of vascular remodeling. In this study, we describe an inhibitor of active PAI-1, WAY-140312. Using fluorescence spectroscopy, it was determined that WAY-140312 bound PAI-1 at a single binding site with a dissociation constant of 5 microM. In a biochemical assay determining direct tPA activity, human recombinant PAI-1 completely inhibited tPA, but this inhibition was blocked by WAY-140312 at an IC(50) of 15.6 microM. In vivo, a 10 mg/kg oral dose of WAY-140312 to rats produced a significant plasma reduction of active PAI-1. Bleeding time, thrombin clotting time, and ex vivo platelet aggregation induced by ADP (20 microM) or collagen (2.5 microg/ml) were not affected by administration of WAY-140312. These results are the first to demonstrate that an orally active PAI-1 inhibitor can reduce plasma PAI-1 activity while maintaining normal platelet aggregation and coagulation." @default.
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• W2056549607 date "2003-11-01" @default.
• W2056549607 modified "2023-09-26" @default.
• W2056549607 title "WAY-140312 reduces plasma PAI-1 while maintaining normal platelet aggregation" @default.
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• W2056549607 doi "https://doi.org/10.1016/j.bbrc.2003.10.088" @default.
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