Selective, orally active inhibitor of plasminogen activator inhibitor-1 (PAI-1; IC50 value 6.95 µM in tissue plasminogen activator-dependent peptide hydrolysis essay) with antithrombotic benefits devoid of bleeding effect in rodents and nonhuman primates, and with impressive bioavailability.TM 5275 prolongs tPA retention and enhances plasmin generation on the vascular endothelial cell (VEC) surface as a result of PAI-1 inhibition.
Additionally, TM 5275 represents a novel class of anti-inflammatory agents targeting macrophage migration by the inhibition of the interaction of PAI-1 with low-density lipoprotein receptor–related protein (IC50 values 3.13 µM and 3.02 µM for LRP1 protein Cl II and Cl IV, respectively).