DX-9065a, a New Synthetic, Potent Anticoagulant and Selective Inhibitor for Factor Xa

Tsuyoshi Hara; Asako Yokoyama; Hiroaki Ishihara; Yukio Yokoyama; Takayasu Nagahara; Masahiro Iwamoto

doi:10.1055/s-0038-1642436

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1994; 71(03): 314-319
DOI: 10.1055/s-0038-1642436

Original Article

Schattauer GmbH Stuttgart

DX-9065a, a New Synthetic, Potent Anticoagulant and Selective Inhibitor for Factor Xa

Authors

Tsuyoshi Hara

The Exploratory Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan
Asako Yokoyama

The Exploratory Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan
Hiroaki Ishihara

The Exploratory Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan
Yukio Yokoyama

The Exploratory Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan
Takayasu Nagahara

The Exploratory Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan
Masahiro Iwamoto

The Exploratory Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan

Abstract

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Summary

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 and PT. Its doubling concentrations for clotting times of each coagulation assay were 0.49, 0.97 and 0.52 μM, respectively. Kinetic study revealed that DX-9065a inhibited competitively human factor Xa (Ki value: 41 μM). Ki values (pM) for other human serine proteases were as follows; thrombin >2000, trypsin 0.62, chymotrypsin >2000, plasmin 23, t-PA 21, plasma kallikrein 2.3 and tissue kallikrein 1000. DX-9065a up to 100 μM had no effects on human platelet aggregation. After intravenous or oral administration, DX-9065a significantly prolonged APTT 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 become an anticoagulant by means of the specific inhibition of factor Xa.

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References

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