Abstract
NF-6505, a bi- O-Tyr-sulfated decapeptide, which specifically interacts with the anion-binding exosite of the thrombin molecule, was chemically synthesized and assessed for its antithrombotic effects in vitro and in vivo. The IC 50 value of this peptide on fibrin-clot formation in vitro was about 0.05 μg/ml, which indicated a potency similar to that of a recombinant hirudin. NF-6505 caused a 2-fold prolongation of activated partial thromboplastin time when intravenously administered at 1 mg/kg in rats. In a rat venous thrombosis model, a bolus intravenous administration of this peptide dose-dependently inhibited the thrombus formation with an ED 50 value of 0.03 mg/kg, a value smaller than that of recombinant hirudin (ED 50 = 0.1 mg/kg) or of argatroban (ED 50 = 0.2 mg/kg). These results suggest that NF-6505 is a highly potent and safe agent for the clinical treatment of venous thrombosis diseases. © 1997 Elsevier Science Ltd
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