Dabigatran Acylglucuronide, the Major Metabolite of Dabigatran, Shows a Weaker Anticoagulant Effect than Dabigatran

Figure 1. Inhibition of thrombin generation by DAB and DABG (n = 5). (A) Cmax; (B) AUC; (C) Lag time and (D) Tmax. *, p < 0.05; **, p < 0.01; ***, p < 0.001.

Figure 2. Representative thrombin-generation inhibition by DAB (A) and DABG (B).

Figure 3. Anticoagulant effects of DAB and DABG assessed by PT (A), aPTT (B), TT (C), and fibrinogen (D) (n = 5). *, p < 0.05; **, p < 0.01; ***, p < 0.001.

Figure 4. Additive inhibitory effect of co-treatment with DAB and DABG on thrombin-generation assay (n = 5). (A), Cmax; (B), AUC; (C), lag time; (D), Tmax.

Figure 5. Docking-simulation results between thrombin and ligands. (A) Binding affinity energies obtained from the top-hit docking mode of DAB and DABG using Autodock Vina. Docking conformation of DAB with thrombin with (B) cartoon plot and (C) protein surface plot. Docking conformation of DABG with thrombin with (D) cartoon plot and (E) protein surface plot. Docking results and hydrogen bonding were visualized using PyMOL (v2.3.5).