Inhibition of probe substrate activity by AMG 853 or M1 in HLM
| CYP Isoform | Probe | Test Article | Ki | Inhibition Model |
|---|---|---|---|---|
| μM | ||||
| CYP1A2 | Phenacetin (7.5–60 μM) | AMG 853 | >30 | |
| M1 | >30 | |||
| CYP2B6 | Bupropion (25–200 μM) | AMG 853 | >30 | |
| M1 | >30 | |||
| CYP2C8 | Paclitaxel (3.5–30 μM) | AMG 853 | 1.1 ± 0.2 | Competitive |
| M1 | 2.7 ± 0.5 | Linear-mixed | ||
| Rosiglitazone (1–20 μM) | AMG 853 | 6.0 ± 0.8 | Competitive | |
| M1 | 6.9 ± 1.4 | Linear-mixed | ||
| Montelukast (0.035–0.75 μM) | AMG 853 | 1.8 ± 1.0 | Biphasic | |
| M1 | 7.3 ± 3.3 | Biphasic | ||
| CYP2C9 | Diclofenac (5–40 μM) | AMG 853 | >30 | |
| M1 | >30 | |||
| CYP2C19 | (S)-Mephenytoin (10–80 μM) | AMG 853 | >30 | |
| M1 | >30 | |||
| CYP2D6 | Dextromethorphan (1–12 μM) | AMG 853 | >30 | |
| M1 | >30 | |||
| CYP2E1 | Chlorzoxazone (25–250 μM) | AMG 853 | >30 | |
| M1 | >30 | |||
| CYP3A4 | Midazolam (0.75–7.5 μM) | AMG 853 | >30 | |
| M1 | >30 | |||
| Testosterone (25–200 μM) | AMG 853 | >30 | ||
| M1 | >30 |