Comparison of parent and metabolite in vitro cytochrome P450 Ki values for Pfizer clinical development candidates
| Metabolite >4× More Potent than Parent (n = 0) | Metabolite 1–4× More Potent than Parent (n = 4) | Metabolite <1× Potent than Parent (n = 10) |
|---|---|---|
| PF-01 -(2×, O-desmethyl, P at 2D6 M at 1A2) | PF-02 -(<1, N-desmethyl, 3A4) | |
| PF-04 -(1×, N-desmethyl, 2B6) | PF-03 -(<0.3, O-glucuronide, 2C9) | |
| PF-04 -(1×, N-oxide, 2D6) | PF-05 -(0.4, methyl catechol, 2D6) | |
| PF-11 -(1×, N-desethyl, 2D6) | PF-06 -(<0.3, N-desethyl, 3A4) | |
| PF-07 -(<0.003, cleaved acid, 2D6) | ||
| PF-08 -(<0.01, cleaved acid (a), 3A4) | ||
| PF-08 -(<0.01, cleaved acid (b), 3A4) | ||
| PF-09 -(P and M inactive, alcohol) | ||
| PF-10 -(P and M inactive, N-desmethyl) | ||
| PF-12 -(0.2, hydroxy, 2C19) |
P, parent; M, metabolite; (fold change potency, metabolite structure, cytochrome P450).