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

Richard C. Becker; John Alexander; You Fu Li; Edwin Bovill; Frederick A. Spencer; Thomas L. Robertson; Satoshi Kunitada; Christopher K. Dyke; Robert A. Harrington

doi:10.1055/s-0037-1614301

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(06): 1229-1231
DOI: 10.1055/s-0037-1614301

Theme Issue Letter to the Editor

Schattauer GmbH

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

Authors

Richard C. Becker

¹Cardiovascular Thrombosis Center, Duke University Medical Center, Durham, North Carolina, USA

²Duke Clinical Research Institute Durham, North Carolina, USA
John Alexander

¹Cardiovascular Thrombosis Center, Duke University Medical Center, Durham, North Carolina, USA

²Duke Clinical Research Institute Durham, North Carolina, USA
You Fu Li

³Laboratory for Vascular Biology Research, UMASS Memorial Medical Center,Worcester, Massachusetts, USA
Edwin Bovill

⁴Department of Pathology, University of Vermont, Burlington, Vermont, USA
Frederick A. Spencer

³Laboratory for Vascular Biology Research, UMASS Memorial Medical Center,Worcester, Massachusetts, USA
Thomas L. Robertson

⁵Daiichi Pharmaceuticals, Inc.,Tokyo, Japan
Satoshi Kunitada

⁵Daiichi Pharmaceuticals, Inc.,Tokyo, Japan
Christopher K. Dyke

¹Cardiovascular Thrombosis Center, Duke University Medical Center, Durham, North Carolina, USA

²Duke Clinical Research Institute Durham, North Carolina, USA
Robert A. Harrington

¹Cardiovascular Thrombosis Center, Duke University Medical Center, Durham, North Carolina, USA

²Duke Clinical Research Institute Durham, North Carolina, USA

Abstract

Full Text

References

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.