TABLE 3

Mean and standard deviations of the mean for three determinations of IC50 values for CYPIA2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4


Compound

Fluorogenic

Conventional
Mean
S.D.
Mean
S.D.
A. CYP1A2
CMPD-1A2-1 0.05 0.02 0.15 0.01
CMPD-1A2-2 >30 >30
CMPD-1A2-3 1.7 0.35 14.9 3.6
CMPD-1A2-4 0.39 0.04 1.6 0.20
CMPD-1A2-5 >30 >30
CMPD-1A2-6 0.04 0.00 0.09 0.01
CMPD-1A2-7 0.78 0.05 0.72 0.21
CMPD-1A2-8 4.2 0.62 16.3 2.2
CMPD-1A2-9 0.10 0.01 0.70 0.13
CMPD-1A2-10 >30 >30
CMPD-1A2-11 11.1 0.82 18.1 3.3
Furafylline 1.1 0.09 1.9 0.54
CMPD-1A2-13 0.40 0.02 1.3 0.45
CMPD-1A2-14 >30 >30
CMPD-1A2-15 >30 >30
CMPD-1A2-16 0.65 0.03 3.8 0.24
CMPD-1A2-17 0.16 0.01 1.1 0.08
CMPD-1A2-18 4.28 0.20 17.2 1.2
CMPD-1A2-19 12.5 1.48 >30
CMPD-1A2-20 >30 >30
CMPD-1A2-21 9.5 0.82 >30
CMPD-1A2-22 0.07 0.00 0.56 0.13
CMPD-1A2-23 <0.03 0.17 0.07
Furafylline 1.1 0.08 2.9 0.78
CMPD-1A2-25 5.8 0.57 7.9 0.62
CMPD-1A2-26 0.11 0.01 0.58 0.01
CMPD-1A2-27 0.18 0.01 0.81 0.04
CMPD-1A2-28 2.2 0.11 6.4 0.36
CMPD-1A2-29 1.5 0.15 1.2 0.09
CMPD-1A2-30 0.26 0.03 1.9 0.13
CMPD-1A2-31 1.4 0.02 5.0 0.42
CMPD-1A2-32 2.6 0.15 3.4 0.19
CMPD-1A2-33 >30 >30
CMPD-1A2-34 0.07 0.01 0.43 0.03
CMPD-1A2-35 >30 >30
Furafylline 1.1 0.11 1.5 0.23
Amitriptyline >30 >30
Caffeine >30 >30
Clozapine >30 >30
Warfarin >30 >30
Haloperidol >30 >30
β-Estradiol >30 >30
Propranolol 1.4 0.17 3.84 0.63
Theophylline >30 >30
Verapamil >30 >30
Cimetidine >30 >30
Tacrine 1.5 0.02 5.2 0.49
Furafylline 0.64 0.04 1.2 0.16
Phanacetin >30 28.0 0.46
Acetanilide >30 >30
Ticlopidine 3.7 0.72 6.1 0.45
Mexiletine 2.8 0.72 1.84 0.27
Riluzole 6.9 0.59 15.8 0.26
Amiodarone >30 >30
Ellipticine 0.06 0.00 0.11 0.01
Cyclobenzaprine >30 >30
8-Methoxypsoralen 0.06 0.01 0.05 0.00
Imiprimine >30 >30
α-Naphthoflavone >30 0.08 0.02
Furafylline 2.5 0.51 1.6 0.05
B. CYP2C9
CMPD-2C9-1 0.47 0.21 9.1 1.1
CMPD-2C9-2 20.4 7.6 >30
CMPD-2C9-3 0.45 0.14 1.6 0.11
CMPD-2C9-4 11.5 4.1 >30
CMPD-2C9-5 >30 >30
CMPD-2C9-6 7.5 1.0 >30
CMPD-2C9-7 1.1 0.23 2.0 1.5
CMPD-2C9-8 0.86 0.31 6.1 1.3
CMPD-2C9-9 0.06 0.01 0.14 0.00
CMPD-2C9-10 >30 >30
CMPD-2C9-11 4.9 1.5 1.7 0.06
Sulfaphenazole 0.34 0.06 2.3 0.24
CMPD-2C9-13 0.20 0.05 1.5 0.09
CMPD-2C9-14 >30 >30
CMPD-2C9-15 2.2 0.29 7.6 0.76
CMPD-2C9-16 4.5 0.67 21.3 0.62
CMPD-2C9-17 0.65 0.10 2.4 0.38
CMPD-2C9-18 0.66 0.09 5.9 1.7
CMPD-2C9-19 0.20 0.04 0.42 0.06
CMPD-2C9-20 1.6 0.19 4.3 0.92
CMPD-2C9-21 2.0 0.17 15.2 3.3
CMPD-2C9-22 0.05 0.01 0.08 0.01
CMPD-2C9-23 0.52 0.10 5.5 5.7
Sulfaphenazole 0.26 0.03 2.5 0.13
CMPD-2C9-25 0.57 0.07 2.7 0.67
CMPD-2C9-26 0.26 0.02 2.8 0.97
CMPD-2C9-27 0.75 0.06 3.4 0.86
CMPD-2C9-28 0.78 0.12 8.6 0.57
CMPD-2C9-29 0.25 0.03 1.6 0.08
CMPD-2C9-30 20.7 3.9 >30
CMPD-2C9-31 1.6 0.12 19.8 3.3
CMPD-2C9-32 4.4 0.26 14.5 0.35
CMPD-2C9-33 0.16 0.01 0.68 0.05
CMPD-2C9-34 0.26 0.02 1.1 0.02
CMPD-2C9-35 0.11 0.00 0.61 0.06
Sulfaphenazole 0.32 0.03 2.1 0.41
CMPD-2C9-37 >30 >30
CMPD-2C9-38 3.0 2.2 5.4 0.30
CMPD-2C9-39 1.6 1.2 19.6 1.4
CMPD-2C9-40 3.2 0.85 >30
CMPD-2C9-41 0.08 0.01 2.0 0.37
CMPD-2C9-42 17.3 11.2 >30
CMPD-2C9-43 0.79 0.33 4.9 0.55
Warfarin >30 21.6 2.4
Amiptriptyline 12.6 0.49 >30
Ibuprofen >30 19.1 3.0
Tamoxifen 4.5 2.0 10.2 2.1
Sulfaphenazole 0.18 0.06 2.9 0.65
Diclofenac/MFC 6.1 3.1 >30
Suprofen 6.7 3.3 >30
Naprozen >30 >30
Fluoxetine 7.0 0.72 >30
Phenylbutazone 5.9 2.4 >30
Coumarin >30 >30
Amitriptyline >30 >30
Phenytoin >30 >30
Amiodarone >30 >30
Ibuprofen >30 >30
Tamoxifen 7.3 1.5 10.2 1.2
Sulfaphenazole 0.25 0.01 2.4 0.72
C. CYP2C19
CMPD-2C19-1 0.45 0.04 0.54 0.02
CMPD-2C19-2 0.33 0.05 0.75 0.04
CMPD-2C19-3 0.07 0.01 0.11 0.00
CMPD-2C19-4 25.1 2.2 11.4 0.70
CMPD-2C19-5 0.52 0.03 0.43 0.01
CMPD-2C19-6 2.2 0.49 4.8 1.8
CMPD-2C19-7 0.63 0.15 2.1 0.66
CMPD-2C19-8 >30 >30
CMPD-2C19-9 0.86 0.15 1.8 0.22
CMPD-2C19-10 0.51 0.04 0.91 0.03
CMPD-2C19-11 0.57 0.08 1.7 0.52
Ticlopidine 0.20 0.01 0.42 0.01
CMPD-2C19-13 1.2 0.14 2.3 0.17
CMPD-2C19-14 6.1 0.38 1.5 0.08
CMPD-2C19-15 0.35 0.05 0.44 0.02
CMPD-2C19-16 0.40 0.04 1.07 0.05
CMPD-2C19-17 3.7 0.53 7.4 0.62
CMPD-2C19-18 0.09 0.00 0.18 0.01
CMPD-2C19-19 4.6 0.09 11.1 0.50
CMPD-2C19-20 0.59 0.06 0.89 0.06
CMPD-2C19-21 0.04 0.01 0.04 0.00
CMPD-2C19-22 1.3 0.12 1.8 0.05
CMPD-2C19-23 1.9 0.15 4.0 0.62
Ticlopidine 0.17 0.02 0.36 0.05
CMPD-2C19-25 1.7 0.34 3.9 0.03
CMPD-2C19-26 1.0 0.19 2.1 0.23
CMPD-2C19-27 3.0 1.4 11.6 1.3
CMPD-2C19-28 0.14 0.03 0.37 0.02
CMPD-2C19-29 0.58 0.09 2.2 0.21
CMPD-2C19-30 1.1 0.20 2.9 0.12
CMPD-2C19-31 0.18 0.02 0.15 0.01
CMPD-2C19-32 0.53 0.10 1.1 0.10
CMPD-2C19-33 0.83 0.14 1.5 0.11
CMPD-2C19-34 0.07 0.01 0.27 0.00
CMPD-2C19-35 0.20 0.03 0.67 0.04
Ticlopidine 0.16 0.03 0.35 0.05
CMPD-2C19-37 1.2 0.18 2.4 0.12
CMPD-2C19-38 0.68 0.14 0.40 0.02
CMPD-2C19-39 1.2 0.18 3.8 0.45
CMPD-2C19-40 0.16 0.03 0.32 0.02
CMPD-2C19-41 0.36 0.05 0.29 0.02
CMPD-2C19-42 >30 >30
CMPD-2C19-43 22.9 1.8 >30
CMPD-2C19-44 2.7 0.61 9.4 2.4
CMPD-2C19-45 2.1 0.30 5.5 0.36
Progesterone 2.8 0.75 4.1 0.33
Indomethicin >30 >30
Ticlopidine 0.18 0.03 0.41 0.04
Amitriptyline 3.1 0.93 3.3 1.2
Warfarin >30 >30
Imipramine 15.3 2.3 27.4
Tranylcypromine 3.4 0.08 8.2 0.67
Omeprazole 0.89 0.02 2.1 0.36
Proranolol >30 >30
Cyclophosphamide >30 >30
Cimetidine 27.6 28.0
Pentamidine >30 >30
Fluoxetine 0.14 0.01 0.11 0.02
Felbamate >30 >30
Ticlopidine 0.17 0.02 0.40 0.04
D. CYP2D6
CMPD-2D6-1 0.13 0.02 <0.03
CMPD-2D6-2 3.3 0.07 4.2 1.3
CMPD-2D6-3 0.12 0.02 <0.03
CMPD-2D6-4 1.2 0.15 0.06 0.01
CMPD-2D6-5 2.6 0.35 0.89 0.19
CMPD-2D6-6 0.32 0.03 0.13 0.03
CMPD-2D6-7 0.62 0.12 0.19 0.05
CMPD-2D6-8 0.13 0.01 <0.03
CMPD-2D6-9 2.6 0.32 0.81 0.07
CMPD-2D6-10 1.8 0.25 0.58 0.07
CMPD-2D6-11 5.2 0.28 5.6 0.20
Quinidine 0.021 0.004 0.006 0.000
CMPD-2D6-13 0.41 0.06 0.33 0.06
CMPD-2D6-14 0.62 0.13 0.18 0.02
CMPD-2D6-15 4.1 0.61 3.0 0.66
CMPD-2D6-16 0.35 0.09 0.05 0.01
CMPD-2D6-17 0.08 0.02 <0.03
CMPD-2D6-18 19.9 2.4 14.5 2.3
CMPD-2D6-19 2.1 0.43 0.38 0.04
CMPD-2D6-20 >30 >30
CMPD-2D6-21 2.1 0.40 3.0 0.18
CMPD-2D6-22 0.05 0.01 <0.03
CMPD-2D6-23 2.4 0.41 1.1 0.09
Quinidine 0.016 0.002 0.006 0.001
CMPD-2D6-25 0.51 0.03 <0.03
CMPD-2D6-26 1.4 0.04 0.80 0.13
CMPD-2D6-27 20.5 4.0 >30
CMPD-2D6-28 1.6 0.16 2.9 0.59
CMPD-2D6-29 0.15 0.01 0.15 0.01
CMPD-2D6-30 0.94 0.12 1.2 0.12
CMPD-2D6-31 1.4 0.12 2.8 0.06
CMPD-2D6-32 0.69 0.09 0.15 0.01
CMPD-2D6-33 0.31 0.05 0.06 0.01
CMPD-2D6-34 0.37 0.07 <0.03
CMPD-2D6-35 0.07 0.01 0.03 0.00
Quinidine 0.016 0.001 0.005 0.001
CMPD-2D6-37 24.0 0.32 19.2 5.0
CMPD-2D6-38 0.34 0.07 0.18 0.01
CMPD-2D6-39 0.19 0.03 <0.03
CMPD-2D6-40 6.9 0.67 5.1 0.15
CMPD-2D6-41 5.0 0.99 6.4 1.1
CMPD-2D6-42 0.65 0.11 1.4 0.46
CMPD-2D6-43 0.17 0.04 0.32 0.08
CMPD-2D6-44 6.6 1.1 4.3 0.44
CMPD-2D6-45 2.6 0.27 7.3 1.2
CMPD-2D6-46 0.03 0.01 >30
Sparteine 22.0 5.8 21.0 3.9
Quinidine 0.015 0.001 0.005 0.001
Bufuralol/AMMC 11.7 3.2 6.1 1.6
Imipramine 2.7 0.96 3.8 0.99
Tamoxifen 17.1 7.0 5.4 1.1
Debrisoquin 9.4 3.9 >30
Clomipramine 1.4 0.46 1.6 0.17
Fluoxetine 0.50 0.18 1.4 0.36
Perphenazine 0.16 0.04 <0.03
Nortriptyline 3.5 1.4 2.2 0.29
Metoprolol 12.7 3.5 >30
Timolol 3.4 0.09 22.6 0.37
Alprenolol 18.6 9.7 2.2 0.89
Quinidine 0.017 0.004 0.006 0.001
E. CYP3A4
CMPD-3A4-1 14.8 5.8 >30
CMPD-3A4-2 >30 2.3 0.05
CMPD-3A4-3 >30 >30
CMPD-3A4-4 >30 2.9 0.18
CMPD-3A4-5 >30 4.9 0.15
CMPD-3A4-6 >30 >30
CMPD-3A4-7 5.4 5.6 0.11 0.01
CMPD-3A4-8 16.1 1.5 2.1 0.24
CMPD-3A4-9 0.87 0.05 0.74 0.10
CMPD-3A4-10 1.7 0.11 4.2 1.2
CMPD-3A4-11 >30 22.0 2.5
Ketoconazole 0.020 0.003 0.059 0.008
CMPD-3A4-13 11.6 0.09 4.2 0.55
CMPD-3A4-14 >30 >30
CMPD-3A4-15 0.96 0.07 0.36 0.01
CMPD-3A4-16 7.1 0.65 0.90 0.09
CMPD-3A4-17 >30 3.6 0.16
CMPD-3A4-18 >30 >30
CMPD-3A4-19 11.7 0.85 2.1 0.15
CMPD-3A4-20 >30 8.7 1.3
CMPD-3A4-21 >30 1.1 0.21
CMPD-3A4-22 5.0 0.19 1.9 0.23
CMPD-3A4-23 1.7 0.04 1.5 0.09
Ketoconazole 0.017 0.002 0.050 0.009
CMPD-3A4-25 19.8 7.8 7.5 0.51
CMPD-3A4-26 >30 1.7 0.14
CMPD-3A4-27 2.2 0.35 2.3 0.58
CMPD-3A4-28 0.94 0.24 0.31 0.04
CMPD-3A4-29 >30 4.9 0.96
CMPD-3A4-30 >30 20.2 0.87
CMPD-3A4-31 0.25 0.01 0.23 0.08
CMPD-3A4-32 0.06 0.01 0.72 0.10
CMPD-3A4-33 12.4 0.69 1.2 0.25
CMPD-3A4-34 0.15 0.02 0.19 0.03
CMPD-3A4-35 >30 >30
Ketoconazole 0.018 0.003 0.040 0.005
CMPD-3A4-37 >30 15.9 0.84
Nifedipine 0.78 0.04 1.7 0.18
CMPD-3A4-39 0.64 0.04 <0.03
Terfenidine >30 0.38 0.06
CMPD-3A4-41 0.30 0.03 1.0 0.16
CMPD-3A4-42 >30 5.2 1.4
CMPD-3A4-43 >30 6.7 1.8
CMPD-3A4-44 >30 2.1 0.52
Quinidine >30 20.5 5.7
Buspirone >30 25.7 1.1
Mifepristone >30 0.25 0.21
Ketoconazole 0.023 0.000 0.040 0.011
Testo/Vivid Red >30 0.52 0.08
CP-16171 (Piroxicam) >30 >30
Erythromycin 4.0 0.35 2.4 0.35
Progesterone >30 16.6 3.2
Hydrocortisone >30 >30
Dextromethorphan >30 >30
Clotrimazole >30 >30
β-Estradiol >30 15.0 2.2
± Verapamil 7.9 1.4 2.0 0.28
Troleandonycin 1.3 0.11 1.0 0.95
Theophylline >30 >30
Ketoconazole
0.016
0.002
0.046
0.007