Figure 7. (A) Time- and concentration-dependent inactivation by
sunitinib of CYP3A4-mediated rivaroxaban metabolism. (B) Observed
inactivation rates (Kobs ) were plotted against
the sunitinib concentration to calculate the inactivation kinetic
constants KI and Kinact .
Each point in Figure 7A was obtained from duplicate experiments.
Molecular docking
simulations
Molecular
docking simulations were used to elucidate the binding conformations for
the interactions between the TKIs and CYP2J2 or CYP3A4. The
corresponding ChemScore values of three TKIs are shown in Figure. 8. In
the docking simulation between CYP2J2 and the TKIs, gefitinib had the
lowest ChemScore value, followed by imatinib and then sunitinib. This
ChemScore ranking was consistent with the inhibitory intensity of the
TKIs on CYP2J2. Additionally, imatinib had the lowest ChemScore value in
the docking simulation with CYP3A4, followed by gefitinib and then
sunitinib, which was also consistent with the inhibitory intensity of
these TKIs on CYP3A4.