ANTITHROMBOTIC EFFECTS OF NF-6505, A NOVEL ANION-BINDING EXOSITE INHIBITOR

NF-6505, a bi-O-Tyr-sulfated decapeptide, which specifically interacts with the anion-binding exosite of the thrombin molecule, was chemical ly synthesized and assessed for its antithrombotic effects in vitro an d in vivo. The IC50 value of this peptide on fibrin-clot formation in vitro was about 0.05 mu g/ml, which indicated a potency similar to tha t of a recombinant hirudin. NF-6505 caused a 2-fold prolongation of ac tivated partial thromboplastin time when intravenously administered at 1 mg/kg in rats. In a rat venous thrombosis model, a bolus intravenou s administration of this peptide dose-dependently inhibited the thromb us formation with an ED50 value of 0.03 mg/kg, a value smaller than th at of recombinant hirudin (ED50 0.1 mg/kg) or of argatroban (ED50 = 0. 2 mg/kg). These results suggest that NF-6505 is a highly potent and sa fe agent for the clinical treatment of venous thrombosis diseases. (C) 1997 Elsevier Science Ltd.