Figure Legends
Figure 1. The initial
screening of imatinib, sunitinib and gefitinib inhibition with: (A) HLM,
(B) CYP2J2 and (C) CYP3A4. The TKI concentrations were 1, 10 and 100 μM.
Results are shown as the mean ± S.D. of at least five determinations.
N.D.: not detectable.
Figure 2. Dose-response
curves of TKI inhibition with (A, D) HLM, (B, E) CYP2J2 and (C, F)
CYP3A4. Results are shown as the mean from at least five experiments.
Figure 3. Reversible
inhibition of CYP2J2 by imatinib and gefitinib. Lineweaver–Burk plots
for the inhibition of (A) imatinib and (C) gefitinib (C) on
CYP2J2-mediated rivaroxaban metabolism; (B) and (D) are the
corresponding Dixon plots. Data represent the
mean
± S.D.
Figure 4. Reversible inhibition of CYP3A4 by imatinib,
gefitinib and sunitinib. Lineweaver–Burk plots for the inhibition of
(A) imatinib, (C) gefitinib and (E) sunitinib on CYP3A4-mediated
rivaroxaban metabolism; (B), (D) and (F) are the corresponding Dixon
plots. Data represent the mean ± S.D.
Figure 5. Effects of
imatinib, sunitinib and gefitinib on rivaroxaban metabolism by (A, B and
C) CYP2J2 and (D, E and F) CYP3A4 with or without a 30-min
pre-incubation in the presence of NADPH. Data points are from five
independent experiments.
Figure 6. (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 .
Figure 7. Molecular docking
simulations of imatinib (A), sunitinib (B) and gefitinib (C) with
CYP2J2, and (D, E and F) with CYP3A4.