Table 1.
IC50 values of vitamin K antagonists
| Compound class | Compound | Chemical structure | VKORC1 IC50 nM (95% CI) | VKORC1L1 IC50 nM (95% CI) | Ratio L1/C1 |
|---|---|---|---|---|---|
| Inactive backbone | Coumarin |  | Not inhibitory* | Not inhibitory* | NA |
| Active 4HC backbone | 4-hydroxycoumarin |  | 1978 (1837-2130) | 25110 (18530-34020) | 12.7 |
| Naturally occurring and therapeutic 4HC | Dicoumarol |  | 5.0† | 100.0† | 20.0 |
| Human therapeutic 4HC | Warfarin |  | 1.9 (1.8-2.1) | 25.2 (23.1-27.4) | 13.4 |
| Human therapeutic 4HC | Acenocoumarol |  | 1.5 (1.4-1.7) | 5.8 (5.4-6.2) | 3.9 |
| Human therapeutic 4HC | Phenprocoumon |  | 3.6 (3.3-3.9) | 10.5 (8.8-12.4) | 2.9 |
| Human therapeutic indandione | Phenindione |  | 2.9 (2.6-3.3) | 258.0 (213.4-312.0) | 89.0 |
| Human therapeutic indandione | Fluindione |  | 4.8 (4.3-5.2) | 268.5 (198.4-363.4) | 55.9 |
| First-generation rodenticide | Coumatetralyl |  | 1.9 (1.8-2.1) | 2.8 (2.7-3.0) | 1.5 |
| First-generation rodenticide | Coumachlor |  | 0.7 (0.6-0.8) | 1.0 (0.8-1.1) | 1.4 |
| Second-generation rodenticide | Bromadiolone |  | 1.6 (1.5-1.7) | 0.8 (0.8-0.9) | 0.5 |
| Second-generation rodenticide | Brodifacoum |  | 0.5 (0.5-0.6) | 0.4 (0.4-0.5) | 0.8 |
| Naturally occurring 4HC | Ferulenol |  | 0.8 (0.8-0.9) | 3.0 (2.4-3.8) | 3.8 |
| Compound class | Compound | Chemical structure | VKORC1 IC50 nM (95% CI) | VKORC1L1 IC50 nM (95% CI) | Ratio L1/C1 |
|---|---|---|---|---|---|
| Inactive backbone | Coumarin | | Not inhibitory* | Not inhibitory* | NA |
| Active 4HC backbone | 4-hydroxycoumarin | | 1978 (1837-2130) | 25110 (18530-34020) | 12.7 |
| Naturally occurring and therapeutic 4HC | Dicoumarol | | 5.0† | 100.0† | 20.0 |
| Human therapeutic 4HC | Warfarin | | 1.9 (1.8-2.1) | 25.2 (23.1-27.4) | 13.4 |
| Human therapeutic 4HC | Acenocoumarol | | 1.5 (1.4-1.7) | 5.8 (5.4-6.2) | 3.9 |
| Human therapeutic 4HC | Phenprocoumon | | 3.6 (3.3-3.9) | 10.5 (8.8-12.4) | 2.9 |
| Human therapeutic indandione | Phenindione | | 2.9 (2.6-3.3) | 258.0 (213.4-312.0) | 89.0 |
| Human therapeutic indandione | Fluindione | | 4.8 (4.3-5.2) | 268.5 (198.4-363.4) | 55.9 |
| First-generation rodenticide | Coumatetralyl | | 1.9 (1.8-2.1) | 2.8 (2.7-3.0) | 1.5 |
| First-generation rodenticide | Coumachlor | | 0.7 (0.6-0.8) | 1.0 (0.8-1.1) | 1.4 |
| Second-generation rodenticide | Bromadiolone | | 1.6 (1.5-1.7) | 0.8 (0.8-0.9) | 0.5 |
| Second-generation rodenticide | Brodifacoum | | 0.5 (0.5-0.6) | 0.4 (0.4-0.5) | 0.8 |
| Naturally occurring 4HC | Ferulenol | | 0.8 (0.8-0.9) | 3.0 (2.4-3.8) | 3.8 |
Overview of OACs investigated in the study, including their compound class as well as IC50 assessed in VKORC1L1 KO and VKORC1 KO HEK 293T cells, using K1 as substrate. Measurements were performed in triplicates.
4HC, 4-hydroxycoumarin; 95% CI, 95% confidence interval; C1, VKORC1; L1, VKORC1L1; NA, not applicable.
*
VKR enzyme activities assessed up to 1 mM coumarin.
†
Biphasic dose-response, no-curve fit with logistic function (VKORC1, 49.1%; VKORC1L1, 48.2% mean normalized activities with respect to 0 nM dicoumarol).