IC50 of clinically used oral anticoagulants for naturally occurring VKOR mutations
| VKOR mutations . | IC50 ± standard deviation, nM . | |||
|---|---|---|---|---|
| Warfarin . | Phenprocoumon . | Acenocoumarol . | Fluindione . | |
| Wild type | 5.1 ± 0.5 | 4.2 ± 0.6 | 0.81 ± 0.12 | 6.6 ± 0.7 |
| A26P | 367 ± 32 | 83.3 ± 6.0 | 7.84 ± 1.13 | 135 ± 42 |
| A26T | 9.8 ± 1.9 | 17.7 ± 2.3 | 1.40 ± 0.16 | 30.2 ± 7.3 |
| L27V | 7.2 ± 0.4 | 8.7 ± 0.8 | 1.25 ± 0.21 | 21.1 ± 1.2 |
| H28Q | 6.6 ± 0.7 | 10.3 ± 1.6 | 0.54 ± 0.06 | 25.9 ± 2.0 |
| V29L | 98 ± 19 | 146 ± 16 | 3.65 ± 0.32 | 95 ± 25 |
| A34P | 99 ± 20 | 128 ± 20 | 1.91 ± 0.23 | 72 ± 17 |
| D36G | 10.5 ± 2.4 | 13.6 ± 1.8 | 0.80 ± 0.09 | 11.5 ± 0.8 |
| D36Y | 6.4 ± 0.8 | 5.1 ± 0.4 | 1.14 ± 0.15 | 9.0 ± 0.2 |
| A41S | 9.5 ± 1.2 | 19.5 ± 1.9 | 0.73 ± 0.07 | 12.8 ± 1.4 |
| V45A | 13.2 ± 2.9 | 17.7 ± 2.2 | 0.91 ± 0.09 | 30.5 ± 1.0 |
| S52L | 119 ± 20 | 87 ± 22 | 2.07 ± 0.14 | 141 ± 16 |
| S52W | 33.5 ± 5.0 | 21.9 ± 4.0 | 1.95 ± 0.21 | 81 ± 13 |
| V54L | 43.2 ± 6.9 | 28.5 ± 1.9 | 6.04 ± 0.79 | 152 ± 19 |
| S56F | 8.4 ± 1.1 | 9.0 ± 2.0 | 1.13 ± 0.07 | 15.0 ± 1.3 |
| R58G | 30.8 ± 3.0 | 14.7 ± 2.8 | 1.16 ± 0.08 | 27.6 ± 3.3 |
| W59R | 500 ± 43 | 835 ± 142 | 11.21 ± 1.47 | 742 ± 76 |
| W59C | 100 ± 12 | 292 ± 23 | 3.81 ± 0.48 | 85.4 ± 5.1 |
| W59L | 431 ± 58 | 398 ± 45 | 6.19 ± 0.79 | 370 ± 58 |
| V66G | 19.9 ± 3.0 | 12.8 ± 2.0 | 1.23 ± 0.16 | 68 ± 11 |
| V66M | 6.8 ± 1.0 | 17.2 ± 1.8 | 1.36 ± 0.14 | 10.2 ± 1.5 |
| H68Y | 8.1 ± 0.9 | 5.5 ± 0.5 | 0.63 ± 0.04 | 12.5 ± 0.6 |
| G71A | 5.2 ± 0.6 | 8.4 ± 1.4 | 1.46 ± 0.26 | 15.2 ± 1.6 |
| N77S | 30.8 ± 5.3 | 53.0 ± 9.6 | 1.45 ± 0.09 | 124 ± 11 |
| N77Y | 19.8 ± 2.5 | 40.5 ± 9.1 | 1.38 ± 0.09 | 23.1 ± 6.4 |
| 123IN | 17.4 ± 2.0 | 46.4 ± 8.2 | 2.60 ± 0.26 | 54.1 ± 8.0 |
| L128R | 431 ± 61 | 592 ± 103 | 10.11 ± 1.62 | 626 ± 127 |
| Y139H | 24.2 ± 2.3 | 60.7 ± 5.8 | 2.27 ± 0.18 | 77.5 ± 6.3 |
| VKOR mutations . | IC50 ± standard deviation, nM . | |||
|---|---|---|---|---|
| Warfarin . | Phenprocoumon . | Acenocoumarol . | Fluindione . | |
| Wild type | 5.1 ± 0.5 | 4.2 ± 0.6 | 0.81 ± 0.12 | 6.6 ± 0.7 |
| A26P | 367 ± 32 | 83.3 ± 6.0 | 7.84 ± 1.13 | 135 ± 42 |
| A26T | 9.8 ± 1.9 | 17.7 ± 2.3 | 1.40 ± 0.16 | 30.2 ± 7.3 |
| L27V | 7.2 ± 0.4 | 8.7 ± 0.8 | 1.25 ± 0.21 | 21.1 ± 1.2 |
| H28Q | 6.6 ± 0.7 | 10.3 ± 1.6 | 0.54 ± 0.06 | 25.9 ± 2.0 |
| V29L | 98 ± 19 | 146 ± 16 | 3.65 ± 0.32 | 95 ± 25 |
| A34P | 99 ± 20 | 128 ± 20 | 1.91 ± 0.23 | 72 ± 17 |
| D36G | 10.5 ± 2.4 | 13.6 ± 1.8 | 0.80 ± 0.09 | 11.5 ± 0.8 |
| D36Y | 6.4 ± 0.8 | 5.1 ± 0.4 | 1.14 ± 0.15 | 9.0 ± 0.2 |
| A41S | 9.5 ± 1.2 | 19.5 ± 1.9 | 0.73 ± 0.07 | 12.8 ± 1.4 |
| V45A | 13.2 ± 2.9 | 17.7 ± 2.2 | 0.91 ± 0.09 | 30.5 ± 1.0 |
| S52L | 119 ± 20 | 87 ± 22 | 2.07 ± 0.14 | 141 ± 16 |
| S52W | 33.5 ± 5.0 | 21.9 ± 4.0 | 1.95 ± 0.21 | 81 ± 13 |
| V54L | 43.2 ± 6.9 | 28.5 ± 1.9 | 6.04 ± 0.79 | 152 ± 19 |
| S56F | 8.4 ± 1.1 | 9.0 ± 2.0 | 1.13 ± 0.07 | 15.0 ± 1.3 |
| R58G | 30.8 ± 3.0 | 14.7 ± 2.8 | 1.16 ± 0.08 | 27.6 ± 3.3 |
| W59R | 500 ± 43 | 835 ± 142 | 11.21 ± 1.47 | 742 ± 76 |
| W59C | 100 ± 12 | 292 ± 23 | 3.81 ± 0.48 | 85.4 ± 5.1 |
| W59L | 431 ± 58 | 398 ± 45 | 6.19 ± 0.79 | 370 ± 58 |
| V66G | 19.9 ± 3.0 | 12.8 ± 2.0 | 1.23 ± 0.16 | 68 ± 11 |
| V66M | 6.8 ± 1.0 | 17.2 ± 1.8 | 1.36 ± 0.14 | 10.2 ± 1.5 |
| H68Y | 8.1 ± 0.9 | 5.5 ± 0.5 | 0.63 ± 0.04 | 12.5 ± 0.6 |
| G71A | 5.2 ± 0.6 | 8.4 ± 1.4 | 1.46 ± 0.26 | 15.2 ± 1.6 |
| N77S | 30.8 ± 5.3 | 53.0 ± 9.6 | 1.45 ± 0.09 | 124 ± 11 |
| N77Y | 19.8 ± 2.5 | 40.5 ± 9.1 | 1.38 ± 0.09 | 23.1 ± 6.4 |
| 123IN | 17.4 ± 2.0 | 46.4 ± 8.2 | 2.60 ± 0.26 | 54.1 ± 8.0 |
| L128R | 431 ± 61 | 592 ± 103 | 10.11 ± 1.62 | 626 ± 127 |
| Y139H | 24.2 ± 2.3 | 60.7 ± 5.8 | 2.27 ± 0.18 | 77.5 ± 6.3 |