Association rate constants (kass) for the inhibition of procoagulant and anticoagulant blood coagulation proteases by antithrombin complexes with idraparinux and EP compounds in I 0.15, pH 7.4 buffer plus 5mM Ca2+ at 25°C
| Protease . | [AT-EP complex] . | kass (M−1s−1) . | ||||
|---|---|---|---|---|---|---|
| Idraparinux . | EP42675 . | EP217609 . | EP217609-1 . | EP307138-1 . | ||
| Thrombin | — | 1.46 ± 0.01 × 104 | — | — | — | — |
| FXa | 0.001-0.02μM | 6.73 ± 0.16 × 105 | 6.57 ± 0.07 × 105 | 5.51 ± 0.87 × 105 | 6.45 ± 0.27 × 105 | 6.36 ± 0.32 × 105 |
| FIXa | 0.1-0.5μM | 3.87 ± 0.28 × 104 | 3.35 ± 0.13 × 104 | 2.74 ± 0.32 × 104 | 3.12 ± 0.27 × 104 | 2.97 ± 0.22 × 104 |
| TF-FVIIa | 0.5-1μM | 6.48 ± 0.19 × 103 | 4.84 ± 0.05 × 103 | 4.64 ± 0.27 × 103 | 5.21 ± 0.31 × 103 | 5.81 ± 0.08 × 103 |
| FXIa | 1-2μM | 9.92 ± 0.08 × 102 | 5.95 ± 0.07 × 102 | 4.85 ± 0.02 × 102 | 5.93 ± 0.22 × 102 | 4.22 ± 0.04 × 102 |
| FXIIa | 1-2μM | 2.10 ± 0.09 × 103 | 2.80 ± 0.01 × 103 | 2.94 ± 0.15 × 103 | 2.80 ± 0.07 × 103 | 3.20 ± 0.05 × 103 |
| Kallikrein | 0.6-2μM | 2.08 ± 0.07 × 103 | 1.69 ± 0.11 × 103 | 1.81 ± 0.01 × 103 | 1.89 ± 0.13 × 103 | 1.56 ± 0.02 × 103 |
| aPC | 20-30μM | 2.09 ± 0.24 | — | — | — | — |
| tPA | 20-60μM | 1.36 ± 0.02 × 101 | 1.27 ± 0.15 × 101 | 1.27 ± 0.03 × 101 | 1.26 ± 0.01 × 101 | 1.21 ± 0.01 × 101 |
| Plasmin | 0.3-0.6μM | 1.52 ± 0.04 × 104 | 1.09 ± 0.08 × 104 | 1.33 ± 0.06 × 104 | 1.11 ± 0.16 × 104 | 1.21 ± 0.05 × 104 |
| Protease . | [AT-EP complex] . | kass (M−1s−1) . | ||||
|---|---|---|---|---|---|---|
| Idraparinux . | EP42675 . | EP217609 . | EP217609-1 . | EP307138-1 . | ||
| Thrombin | — | 1.46 ± 0.01 × 104 | — | — | — | — |
| FXa | 0.001-0.02μM | 6.73 ± 0.16 × 105 | 6.57 ± 0.07 × 105 | 5.51 ± 0.87 × 105 | 6.45 ± 0.27 × 105 | 6.36 ± 0.32 × 105 |
| FIXa | 0.1-0.5μM | 3.87 ± 0.28 × 104 | 3.35 ± 0.13 × 104 | 2.74 ± 0.32 × 104 | 3.12 ± 0.27 × 104 | 2.97 ± 0.22 × 104 |
| TF-FVIIa | 0.5-1μM | 6.48 ± 0.19 × 103 | 4.84 ± 0.05 × 103 | 4.64 ± 0.27 × 103 | 5.21 ± 0.31 × 103 | 5.81 ± 0.08 × 103 |
| FXIa | 1-2μM | 9.92 ± 0.08 × 102 | 5.95 ± 0.07 × 102 | 4.85 ± 0.02 × 102 | 5.93 ± 0.22 × 102 | 4.22 ± 0.04 × 102 |
| FXIIa | 1-2μM | 2.10 ± 0.09 × 103 | 2.80 ± 0.01 × 103 | 2.94 ± 0.15 × 103 | 2.80 ± 0.07 × 103 | 3.20 ± 0.05 × 103 |
| Kallikrein | 0.6-2μM | 2.08 ± 0.07 × 103 | 1.69 ± 0.11 × 103 | 1.81 ± 0.01 × 103 | 1.89 ± 0.13 × 103 | 1.56 ± 0.02 × 103 |
| aPC | 20-30μM | 2.09 ± 0.24 | — | — | — | — |
| tPA | 20-60μM | 1.36 ± 0.02 × 101 | 1.27 ± 0.15 × 101 | 1.27 ± 0.03 × 101 | 1.26 ± 0.01 × 101 | 1.21 ± 0.01 × 101 |
| Plasmin | 0.3-0.6μM | 1.52 ± 0.04 × 104 | 1.09 ± 0.08 × 104 | 1.33 ± 0.06 × 104 | 1.11 ± 0.16 × 104 | 1.21 ± 0.05 × 104 |
Second-order rate constants for reactions of antithrombin-EP compound complexes with proteases were determined under pseudo–first-order conditions based on exponential fits of reaction progress curves obtained at different concentrations of antithrombin complexes as described in “Methods.” Reported rate constants are average values from at least 2 progress curves with errors representing the range of values.
— indicates not measurable.