Combined coagulation phase-directed factor Xa inhibition with heparin compounds and DX-9065a - A direct and selective antagonist

• References

• 1 Hoffman M, Monroe III DM. A cell-based model of hemostasis. Thromb Haemost 2001; 85: 958-65.
• 2 Rogers KL, Chi L, Rapundalo ST. et al. Effects of factor Xa inhibitor, DX-9065a, in a novel rabbit model of venous thrombosis. Basic Res Cardiol 1999; 94: 15-22.
• 3 Herbert JM, Bernat A, Dol F, Herault JP, Crepon B, Lormeau JC. et al DX-9065a, a novel, synthetic, selective and orally active inhibitor of factor Xa: in vitro and in vivo studies. J Pharmacol Exp Ther 1996; 276: 1030-8.
• 4 Yokoyama T, Kelly AB, Marzec UM. et al. Antithrombotic effects of orally active synthetic antagonist of activated factor X in nonhuman primates. Circulation 1995; 92: 485-91.
• 5 Kim DI, Kambayashi J, Shibuya T. et al. In vivo evaluation of DX-9065a, a synthetic factor Xa inhibitor, in experimental vein graft. J Atheroscler Thromb 1996; 02: 110-16.
• 6 Yamazaki M, Asakura H, Aoshima K. et al. Effects of DX-9065a, an orally active, newly synthesized and specific inhibitor of factor Xa, against experimental disseminated intravascular coagulation in rats. Thromb Haemost 1994; 72: 392-6.
• 7 Dyke CK, Becker RC, Kleiman NS. et al. First experience with direct factor Xa inhibition in patients with stable coronary disease: A pharmacokinetic and pharmacodynamic evaluation. Circulation 2002; 105: 2385-91.
• 8 Armitage P, Berry G. Statistical Methods in Medical Research. Third Edition.. Blackwell Scientific Publications; Boston, MA: 1994: 386-401.
• 9 Sheth SB, DiCicco RA, Hursting MJ, Montague T, Jorkasky DK. et al Interpreting the internationalized normalized ratio (INR) in individuals receiving Argatroban and Warfanin. Thromb Haemost 2001; 85: 435-40.
• 10 Rezaie AR. Identification of basic residues in the heparin-binding exosite of factor Xa critical for heparin and factor Va binding. J Biol Chem 2000; 275: 3320-27.
• 11 Rezaie AR. DX-9065a inhibition of factor Xa and the prothrombinase complex: Mechanism of inhibition and comparison with therapeutic heparins. Thromb Haemost 2003; 89: 112-21.
• 12 Katakura S, Nagahara T, Hara T. et al. Molecular model of an interaction between factor Xa and DX-9065a, a novel factor Xa inhibitor: contribution of the acetimidoylpyrrolidine moiety of the inhibitor to potency and selectivity for serine proteases. Eur J Med Chem 1995; 30: 387-94.
• 13 Brandstetter H, Kühnet A, Bode W. et al. X-ray structure of active site-inhibited clotting factor Xa. J Biol Chemistry 1996; 271: 29988-92.