Table 7

Observed and predicted Ki (apparent) for inhibitors of CYP2C9 fit to different Catalyst CYP2C9 pharmacophores

InhibitorReferenceObserved MicrosomalKi(apparent)Model 17-a Prediction Fast FitKi(apparent)Model 17-a Prediction Best FitKi(apparent)Model 27-b Prediction Fast FitKi(apparent)Model 27-b Prediction Best FitKi(apparent)
μM
R-7-fluorowarfarin Zhang et al., 1997 189.3  (−0.3)3.1  (−0.8)1.2  (−1.2)0.15  (−2.0)
S-7-fluorowarfarin Zhang et al., 1997 <119  (1.3)3.5  (0.5)1.3  (0.1)0.17  (−0.8)
Rac-6-fluorowarfarin Zhang et al., 1997 344.2  (−0.9)0.98  (−1.5)1.1  (−1.5)0.15  (−2.3)
Rac-6,7,8-trifluorowarfarin Zhang et al., 1997 57.9  (0.2)1.4  (−0.5)4.6  (−0.04)0.19  (−1.4)
S-warfarin alcohol Zhang et al., 1997 7.54.7  (−0.2)3  (−0.4)2  (−0.6)0.16  (−1.7)
Ipriflavone Monostory et al., 1998 21.749  (0.3)49  (0.3)27  (0.1)27  (0.1)
7-hydroxyisoflavone Monostory et al., 1998 13.456  (0.6)56  (0.6)30  (0.3)22  (0.2)
Ticlopidine Donahue et al., 1997 38.849  (0.1)33  (−0.1)17  (−0.4)16  (−0.4)
Omeprazole Ko et al., 1997 40.13.8  (−1.0)3.1  (−1.1)2.5  (−1.2)0.24  (−2.2)
Lansoprazole Ko et al., 1997 49.13.6  (−1.1)3.4  (−1.1)15  (−0.5)15  (−0.5)
Sertraline Schmider et al., 1997 338.3  (−0.6)4.8  (−0.8)16  (−0.3)16  (−0.3)
Desmethylsertraline Schmider et al., 1997 666.2  (−1.0)3.8  (−1.2)16  (−0.6)15  (−0.6)
Fluvoxamine Schmider et al., 1997 64.9  (−0.1)3.2  (−0.3)0.58  (−1.0)0.14  (−1.6)
Paroxetine Schmider et al., 1997 355.4  (−0.8)4.8  (−0.9)1.9  (−1.3)1.1  (−1.5)

Values in parentheses represent the residual (log units) of predicted − observed Ki (apparent) values.

  • 7-a  Data used for model construction from Table 1.

  • 7-b  Data used for model construction from Jones et al., 1996b.