Kinetic parameters for metabolism of propranolol analogs by recombinant human CYP2D6
| 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 | 2.5 ± 0.4 | 51.5 ± 1.6 | 20.6 | 6.4 ± 1.0 | 7.9 ± 0.3 | 1.2 | 2.8 ± 0.4 | 7.1 ± 0.2 | 2.5 | 8.4 |
| 2R-P | 1.3 ± 0.2 | 29.1 ± 0.9 | 22.4 | 1.7 ± 1.0 | 5.0 ± 0.6 | 2.9 | 1.5 ± 0.3 | 3.6 ± 0.1 | 2.4 | 9.5 |
| 2S-FP | 1.5 ± 0.6 | 12.9 ± 1.1 | 8.6 | 1.4 ± 0.6 | 3.3 ± 0.3 | 2.4 | 1.5 ± 1.8 | 0.03 ± 0.01 | 0.0 | 540 |
| 2S-DFP | 3.8 ± 0.3 | 18.4 ± 0.3 | 4.8 | 3.4 ± 0.7 | 2.7 ± 0.1 | 0.8 | 3.4 ± 1.5 | 1.7 ± 0.2 | 0.5 | 12.4 |
| 2S-TFP | 76.7 ± 5.2 | 46.7 ± 1.5 | 0.6 | 75.2 ± 6.5 | 14.1 ± 0.6 | 0.2 | 79.2 ± 3.2 | 12.2 ± 0.2 | 0.2 | 5.0 |
| 2S,4R-TFP | 43.1 ± 4 | 27.0 ± 1 | 0.6 | 38.6 ± 0.8 | 13.9 ± 0.1 | 0.4 | 18.8 ± 2.3 | 4.5 ± 0.2 | 0.2 | 9.1 |
| 2R-TFP | 32.3 ± 5.5 | 34.6 ± 1.7 | 1.1 | 33.6 ± 2.3 | 18.9 ± 0.4 | 0.6 | 26.3 ± 11.5 | 4.9 ± 0.6 | 0.2 | 10.9 |
| iPrMe | 0.32 ± 0.07 | 19.8 ± 0.6 | 61.9 | 0.44 ± 0.18 | 6.3 ± 0.4 | 14.3 | 0.41 ± 0.29 | 0.41 ± 0.05 | 1.0 | 63.7 |
| tBuMe | 0.25 ± 0.06 | 7.1 ± 0.2 | 28.4 | 0.17 ± 0.05 | 5.9 ± 0.2 | 34.7 | 0.16 ± 0.06 | 0.14 ± 0.01 | 0.9 | 92.9 |
| TFE | 46.9 ± 5.3 | 25.5 ± 1.1 | 0.5 | 41.6 ± 24 | 5.3 ± 1.2 | 0.1 | 38.6 ± 9.2 | 5.8 ± 0.8 | 0.2 | 5.3 |
| desOHP | 0.16 ± 0.11 | 22.0 ± 2.3 | 139 | 0.22 ± 0.12 | 11.9 ± 1.2 | 54.0 | ||||
| desOHTFP | 9.49 ± 1.20 | 17.9 ± 0.6 | 1.9 | 7.3 ± 1.5 | 19.6 ± 1.0 | 2.7 | 4.8 ± 2.9 | 1.5 ± 0.2 | 0.3 | 25.2 |