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

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
› Author Affiliations
Further Information

Publication History

Received: 22 June 1993

Accepted after revision 12 September 1993

Publication Date:
06 July 2018 (online)

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.