Table 3. Identification of the enzymes causing generation of the insoluble metabolite M3.
| 3a. Formation of metabolites after incubation of JNJ-38877605 with microsomes or 12000 ×g supernatant | |||||
|---|---|---|---|---|---|
| Matrix | metabolites | ||||
|
| |||||
| Microsomes 12000 ×g | M1/M2 | M3 | M4 | UD | |
| 4.46 | 1.21 | 4.07 | 12.8 | ||
| 2.82 | 24.53 | 1.92 | 26.0 | ||
|
| |||||
| 5 μM 3H-JNJ-38877605 was incubated with human liver microsomes or 12000 ×g during 120 min. | |||||
| 3b. Inhibition of the metabolism of JNJ-38877605 and the formation of the major metabolites in human liver supernatant by an inhibitor of aldehyde oxidase and cytochrome P-450. | |||||
|---|---|---|---|---|---|
| M1/M2 | M3 | M4 | UD (sum of all metabolite formation) | ||
|
| |||||
| Inhibitor | Enzyme | % inhibition of metabolite formation | |||
|
| |||||
| Quercetin | Aldehyde oxidase CYP2C8 | 75 | 94 | 73 | 112 |
|
| |||||
| 1-aminobenzotriazole | CYP-450 | 58 | 1 | 70 | 19 |
5 μM 3H-JNJ-38877605 was incubated with human 12000×g liver supernatant.