TABLE 1

Selectivity of reversible and time-dependent inhibition of human P450 enzymes by CYP3cide

Marker Substrate ActivityEnzymeReversible InhibitionTime-Dependent Inhibition*
IsoformConc.Mean ± S.E.PreincubationResult
mg/mlIC50, μMConc., μM%Decrease
Phenacetin O-deethylaseCYP1A20.03043 ± 9100−17
Bupropion hydroxylaseCYP2B60.03088 ± 30100−2.4
Paclitaxel 6α-hydroxylaseCYP2C80.03078 ± 57100−13
Diclofenac 4′-hydroxylaseCYP2C90.030>1001005.4
S-Mephenytoin 4′-hydroxylaseCYP2C190.1077 ± 15100−0.79
Dextromethorphan O-demethylaseCYP2D60.03071 ± 4100−6.0
Felodipine oxidaseCYP3A0.0100.16 ± 0.01N.D.N.D.
Midazolam 1′-hydroxylaseCYP3A0.0100.33 ± 0.04147
Testosterone 6β-hydroxylaseCYP3A0.0101.4 ± 0.1553
Midazolam 1′-hydroxylaserCYP3A40.0100.30 ± 0.020.05087
Testosterone 6β-hydroxylaserCYP3A40.0200.69 ± 0.220.05074
Midazolam 1′-hydroxylaserCYP3A50.01017 ± 2261
Testosterone 6β-hydroxylaserCYP3A50.02071 ± 30271
Midazolam 1′-hydroxylaserCYP3A70.02033 ± 2100−15
  • N.D., not determined.

  • * The preincubation step for the IC25 shift assays were performed for 30 min at 37°C.