Prasa D, Svendsen L, Stürzebecher J
Zentrum für Vaskuläre Biologie und Medizin, Klinikum der Friedrich-Schiller-Universität Jena, Germany.
Thromb Haemost. 1997 Oct;78(4):1215-20.
A series of inhibitors of factor Xa (FXa) were investigated using the thrombin generation assay to evaluate the potency and specificity needed to efficiently block thrombin generation in activated human plasma. By inhibiting FXa the generation of thrombin in plasma is delayed and decreased. Inhibitor concentrations which cause 50 percent inhibition of thrombin generation (IC50) correlate in principle with the Ki values for inhibition of free FXa. Recombinant tick anticoagulant peptide (r-TAP) is able to inhibit thrombin generation with considerably low IC50 values of 49 nM and 37 nM for extrinsic and intrinsic activation, respectively. However, the potent synthetic, low molecular weight inhibitors of FXa (Ki values of about 20 nM) are less effective in inhibiting the generation of thrombin with IC50 values at micromolar concentrations. The overall effect of inhibitors of FXa in the thrombin generation assay was compared to that of thrombin inhibitors. On the basis of similar Ki values for the inhibition of the respective enzyme, synthetic FXa inhibitors are less effective than thrombin inhibitors. In contrast, the highly potent FXa inhibitor r-TAP causes a stronger reduction of the thrombin activity in plasma than the most potent thrombin inhibitor hirudin.
使用凝血酶生成测定法研究了一系列凝血因子Xa（FXa）抑制剂，以评估有效阻断活化人血浆中凝血酶生成所需的效力和特异性。通过抑制FXa，血浆中凝血酶的生成会延迟并减少。导致凝血酶生成50%抑制的抑制剂浓度（IC50）原则上与抑制游离FXa的Ki值相关。重组蜱抗凝肽（r-TAP）能够抑制凝血酶生成，对于外源性和内源性激活，其IC50值分别低至49 nM和37 nM。然而，高效的合成低分子量FXa抑制剂（Ki值约为20 nM）在抑制凝血酶生成方面效果较差，其IC50值处于微摩尔浓度。在凝血酶生成测定中，将FXa抑制剂的总体效果与凝血酶抑制剂的效果进行了比较。基于抑制各自酶的相似Ki值，合成FXa抑制剂的效果不如凝血酶抑制剂。相比之下，高效的FXa抑制剂r-TAP比最强效的凝血酶抑制剂水蛭素更能强烈降低血浆中的凝血酶活性。
