Kinetics values for the metabolism of DY-9760e by recombinant P450 microsomes
Metabolite (Pathway) | P450 | Km | Vmax | Vmax/Km | Vmax2/Km2a | Ks | n (Hill coefficient) | Kinetic Model | |
|---|---|---|---|---|---|---|---|---|---|
| μM | pmol/min/nmol P450 | μl/min/nmol P450 | μM | ||||||
| M3 (phenyl hydroxylation) | CYP1A1 | 1.1 | 16.7 | 15.2 | 438.3 | SI (<50 μM) | |||
| CYP1A2 | 5.2 | 7.3 | 1.4 | 0.02 | 2-site M-M | ||||
| CYP2C8 | 2.5 | 295.5 | 118.2 | 270.0 | SI (weighted) | ||||
| CYP2C9 | 1.2 | 8.6 | 7.2 | M-M | |||||
| CYP2C19 | 1.6 | 9.9 | 6.2 | M-M | |||||
| CYP2D6 | 0.7 | 19.7 | 30.3 | M-M | |||||
| CYP3A4 | 6.9 | 896.1 | 129.9 | 2.4 | AA (<50 μM) | ||||
| M5 (O-demethylation) | CYP2C8 | 3.1 | 12.8 | 4.2 | 0.08 | Biphasic | |||
| CYP2C9 | 0.9 | 71.2 | 79.1 | 363.1 | SI (<200 μM) | ||||
| CYP2C19 | 0.5 | 72.9 | 145.8 | 315.4 | SI (<200 μM) | ||||
| CYP2D6 | 1.0 | 86.9 | 86.9 | M-M | |||||
| CYP3A4 | 11.9 | 29.9 | 2.5 | 0.10 | 2.1 | AA + biphasic | |||
| M6 (imidazole oxidation) | CYP3A4 | 6.5 | 627.5 | 96.5 | 2.6 | AA (<50 μM) | |||
| M7 (O-demethylation) | CYP2C19 | 0.3 | 16.2 | 54.5 | M-M | ||||
| CYP2D6 | 0.6 | 22.1 | 35.5 | M-M | |||||
| CYP3A4 | 14.6 | 308.5 | 21.1 | 1.8 | AA | ||||
| M8 (imidazole oxidation) | CYP1A1 | 1.1 | 198.85 | 153.6 | M-M | ||||
| CYP1A2 | 25.1 | 62.3 | 2.5 | M-M | |||||
| CYP2C8 | 2.6 | 73.2 | 28.2 | M-M | |||||
| CYP2C9 | 6.4 | 13.9 | 2.2 | 0.31 | 2-site M-M | ||||
| CYP2C19 | 9.6 | 50.0 | 5.2 | M-M | |||||
| CYP2D6 | 1.4 | 147.8 | 105.6 | M-M | |||||
| CYP3A4 | 9.0 | 2167.5 | 240.8 | 2.0 | AA | ||||
| DY-9836 (N-dealkylation) | CYP1A1 | 31.1 | 193.6 | 6.2 | M-M | ||||
| CYP1A2 | 24.2 | 76.7 | 3.2 | M-M | |||||
| CYP2C8 | 15.2 | 23.1 | 1.5 | 0.25 | 2-site M-M | ||||
| CYP2C9 | 54.2 | 51.2 | 0.9 | M-M | |||||
| CYP2C19 | 14.3 | 97.4 | 6.8 | 585.2 | SI | ||||
| CYP2D6 | 74.7 | 153.2 | 2.1 | M-M | |||||
|
| CYP3A4 | 7.1 | 1145.3 | 161.3 |
|
| 1.5 | AA | |
SI, substrate inhibition; M-M, Michaelis-Menten; AA, autoactivation.
↵ a Low-affinity site.