DX-9065A, A NEW SYNTHETIC, POTENT ANTICOAGULANT AND SELECTIVE INHIBITOR FOR FACTOR-XA

DX-9065a is an orally active newly synthesized and specific inhibitor for factor Xa. We have examined the property of DX-9065a in vitro and ex vivo. DX-9065a prolonged human plasma recalcification time, APTT an d PT. Its doubling concentrations for clotting times of each coagulati on assay were 0.49, 0.97 and 0.52 muM, respectively. Kinetic study rev ealed that DX-9065a inhibited competitively human factor Xa (Ki value: 41 nM). Ki values (muM) for other human serine proteases were as foll ows; thrombin >2000, trypsin 0.62, chymotrypsin >2000, plasmin 23, t-P A 21, plasma kallikrein 2.3 and tissue kallikrein 1000. DX-9065a up to 100 muM had no effects on human platelet aggregation. After intraveno us or oral administration, DX-9065a significantly prolonged APT and PT with a dose dependent manner. These effects were well correlated with anti-Xa activity in plasma. These results suggest that DX-9065a may b ecome an anticoagulant by means of the specific inhibition of factor X a.