Table 3.
CYP2B6 substrates from the original pharmacophore and test set [5] with molecular properties calculated with ChemSpider.
| Substrate | Reaction | Km (µM) | MW | ACD/logP | LogDpH5.5 | LogDpH7.4 | HBD | HBA | RBN | PSA | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Antipyrine | hydroxylation | 17700 | 188.23 | 0.27 | 0.27 | 0.27 | 0 | 3 | 1 | 23.55 | |
| Benzphetamine | N-demethylation | 93.4 | 239.35 | 4.43 | 1.51 | 2.95 | 0 | 1 | 5 | 3.24 | |
| Benzyloxyresorufin | N-demethylation | 1.28 | 303.31 | 3.15 | 3.15 | 3.15 | 0 | 4 | 3 | 47.89 | |
| Cinnarizine | hydroxylation | 17.2 | 368.51 | 4.63 | 3.47 | 4.56 | 0 | 2 | 6 | 6.48 | |
| 4-chloro-7-ethoxycoumarin | O-deethylation | 33.7 | 224.64 | 2.50 | 2.37 | 2.37 | 0 | 3 | 2 | 35.53 | |
| 3-cyano-7-ethoxycoumarin | O-deethylation | 71.3 | 215.20 | 2.00 | 2.51 | 2.51 | 0 | 4 | 2 | 59.32 | |
| Dextromethorphan | N-demethylation | 350 | 271.40 | 4.11 | 1.12 | 2.39 | 0 | 2 | 1 | 12.47 | |
| Diazepam | N-demethylation | 113 | 284.74 | 2.91 | 2.91 | 2.91 | 0 | 3 | 1 | 32.67 | |
| 1,2-Dibromoethane | 2-bromoacetaldehyde formation | 9700 | 187.86 | 2.08 | 2.08 | 2.08 | 0 | 0 | 1 | 0 | |
| 7-ethoxycoumarin | O-deethylation | 115 | 190.19 | 2.31 | 2.31 | 2.31 | 0 | 3 | 2 | 35.53 | |
| 7-ethoxy-4-trifluoromethylcou marin | O-deethylation | 1.7 | 258.19 | 3.41 | 3.42 | 3.42 | 0 | 3 | 2 | 35.53 | |
| Imipramine | N-demethylation | 383 | 280.41 | 4.80 | 1.76 | 2.79 | 0 | 2 | 4 | 6.48 | |
| Midazolam | Hydroxylation | 46.1 | 325.77 | 3.93 | 3.48 | 3.92 | 0 | 3 | 1 | 30.18 | |
| RP73401 | Hydroxylation | 22.5 | 381.25 | 4.27 | 4.27 | 4.27 | 1 | 5 | 5 | 51.66 | |
| S-mephenytoin | N-demethylation | 564 | 218.25 | 1.40 | 1.4 | 1.32 | 1 | 4 | 2 | 40.62 | |
| Testosterone | Hydroxylation | 50.5 | 288.42 | 3.47 | 3.48 | 3.48 | 1 | 2 | 1 | 26.3 | |
| Amitriptyline | N-demethylation | 144.4 | 277.40 | 4.92 | 1.92 | 3.15 | 0 | 1 | 3 | 3.24 | |
| Bupropion | Hydroxylation | 107.5 | 239.74 | 3.47 | 1.82 | 3.27 | 1 | 2 | 4 | 20.31 | |
| Lidocaine | N-deethylation | 537.6 | 234.34 | 2.36 | −0.13 | 1.57 | 1 | 3 | 5 | 23.55 | |
| Verapamil | O-demethylation Dihydroqinghaosu | 137.4 | 454.60 | 3.90 | 0.95 | 2.33 | 0 | 6 | 13 | 63.95 | |
| Arteether | formation | 28 | 312.40 | 3.60 | 3.6 | 3.6 | 0 | 5 | 2 | 46.15 | |
| Mean | 273.53 | 3.23 | 2.27 | 2.79 | 0.24 | 2.90 | 3.14 | 28.79 | |||
| (±SD) | (68.35) | (1.20) | (1.17) | (1.00) | (0.44) | (1.44) | (2.76) | (18.95) | |||
MW = molecular weight, HBA = hydrogen bond acceptors, HBD = hydrogen bond donors, RBN = rotatable bond number, PSA = polar surface area
For references for the original Km data please refer to [5].