Kinetic data for inhibition of NPC formation by various drugs
| IC50 of Inhibitor | KM of CPT-11 | Vmaxof NPC Formation | |
|---|---|---|---|
| μM | μM | pmol/min/mg of protein | |
| Control | 33.5 ± 2.0 | 103 ± 3 | |
| Ketoconazole | 0.075 | 47.6 ± 2.7 | 67.7 ± 1.8 |
| Troleandomycin | 0.256 | 103 ± 26 | 88.7 ± 13.4 |
| Ondansetron | 43.7 | 57.9 ± 3.3 | 64.5 ± 1.8 |
| Loperamide | 18.1 | 79.5 ± 10.8 | 59.8 ± 4.5 |
| Racecadotril | 46.8 | 44.7 ± 12.0 | 25.0 ± 3.0 |
The IC50 of each inhibitor was first estimated using pooled microsomes with 25 μM CPT-11 lactone, in three independent experiments; we then estimated the effect of this concentration of inhibitor on the kinetic parameters for CPT-11 transformation into NPC with a range of concentrations of CPT-11, also in three independent experiments.