Table 2
Kinetic parameters for metabolism of propranolol analogs by recombinant human CYP1A2
| Substrate | 4′-OH Product | 5′-OH Product | N-Dealkylation Product | Total Ring OH/DIP | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Km | kcat | kcat/Km | Km | kcat | kcat/Km | Km | kcat | kcat/Km | ||
| μM | min−1 | μM | min−1 | μM | min−1 | |||||
| 2S-P | 3.5 ± 0.20 | 4.40 ± 0.20 | 1.3 | 0.0 | ||||||
| 2R-P | 1.5 ± 0.10 | 4.20 ± 0.20 | 2.8 | 0.0 | ||||||
| 2S-FP | 0.83 ± 0.51 | 0.32 ± 0.07 | 0.4 | 0.70 ± 0.10 | 1.60 ± 0.10 | 2.3 | 0.2 | |||
| 2S-DFP | 0.39 ± 0.1 | 1.40 ± 0.10 | 3.6 | 0.33 ± 0.05 | 5.00 ± 0.20 | 15.2 | 0.3 | |||
| 2S-TFP | 0.43 ± 0.12 | 4.00 ± 0.30 | 9.3 | 0.17 ± 0.03 | 0.90 ± 0.03 | 5.3 | 0.18 ± 0.03 | 1.90 ± 0.05 | 10.6 | 2.6 |
| 2R-TFP | 0.56 ± 0.09 | 2.60 ± 0.10 | 4.6 | 0.23 ± 0.02 | 0.86 ± 0.02 | 3.7 | 1.13 ± 0.38 | 7.10 ± 0.80 | 6.3 | 0.5 |
| 2S,4R-TFP | 0.62 ± 0.05 | 1.28 ± 0.03 | 2.1 | 0.28 ± 0.02 | 0.42 ± 0.01 | 1.5 | 0.23 ± 0.02 | 1.45 ± 0.03 | 6.3 | 1.2 |
| iPrMe | 0.76 ± 0.24 | 0.95 ± 0.10 | 1.3 | 0.74 ± 0.12 | 0.50 ± 0.02 | 0.7 | 0.98 ± 0.12 | 3.90 ± 0.20 | 4.0 | 0.4 |
| tBuMe | 0.70 ± 0.16 | 1.37 ± 0.10 | 2.0 | 0.21 ± 0.14 | 0.50 ± 0.07 | 2.4 | 1.40 ± 0.20 | 0.69 ± 0.05 | 0.5 | 2.7 |
| TFE | 0.56 ± 0.12 | 2.83 ± 0.16 | 5.1 | 0.56 ± 0.22 | 0.42 ± 0.04 | 0.8 | 0.15 ± 0.03 | 0.84 ± 0.04 | 5.6 | 3.9 |
| desOHP | 0.82 ± 0.13 | 1.09 ± 0.05 | 1.3 | 0.81 ± 0.14 | 0.30 ± 0.02 | 0.4 | 0.41 ± 0.20 | 0.30 ± 0.04 | 0.7 | 4.6 |
| desOHTFP | 1.42 ± 0.23 | 3.66 ± 0.21 | 2.6 | 0.64 ± 0.1 | 0.49 ± 0.02 | 0.8 | 0.30 ± 0.07 | 0.22 ± 0.01 | 0.7 | 18.9 |
