Hara T, Yokoyama A, Ishihara H, Yokoyama Y, Nagahara T, Iwamoto M
Exploratory Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Thromb Haemost. 1994 Mar;71(3):314-9.
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 microM, respectively. Kinetic study revealed that DX-9065a inhibited competitively human factor Xa (Ki value: 41 nM). Ki values (microM) 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 microM 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.
DX - 9065a是一种新合成的口服活性Xa因子特异性抑制剂。我们已在体外和体内研究了DX - 9065a的特性。DX - 9065a延长了人血浆复钙时间、活化部分凝血活酶时间（APTT）和凝血酶原时间（PT）。其在各凝血试验中使凝血时间加倍的浓度分别为0.49、0.97和0.52微摩尔。动力学研究表明，DX - 9065a竞争性抑制人Xa因子（Ki值：41纳摩尔）。其对其他人类丝氨酸蛋白酶的Ki值（微摩尔）如下：凝血酶>2000、胰蛋白酶0.62、糜蛋白酶>2000、纤溶酶23、组织型纤溶酶原激活剂（t - PA）21、血浆激肽释放酶2.3和组织激肽释放酶1000。高达100微摩尔的DX - 9065a对人血小板聚集无影响。静脉或口服给药后，DX - 9065a以剂量依赖方式显著延长APTT和PT。这些作用与血浆中的抗Xa活性密切相关。这些结果表明，DX - 9065a可能通过特异性抑制Xa因子而成为一种抗凝剂。
