Kinetic analysis of UGTs-induced O-glucuronidation of trans- and cis-endoxifen
All data are the mean ± S.D. based on three independent experiments. Homogenates from cells overexpressing UGTs 1A6, 2B4, 2B10, or 2B11 exhibited no detectable glucuronidating activity against endoxifen.
UGT | trans-Endoxifen | cis-Endoxifen | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Vmax | KM | Vmax/KM | Vmax | KM | Vmax/KM | |||||
| pmol · min−1 · μg−1 | μM | μl · min−1 · μg−1 | pmol · min−1 · μg−1 | μM | μl · min−1 · μg−1 | |||||
| 1A1 | 2.3 ± 0.3 | 333 ± 60 | 0.0069 ± 0.0005 | Low activitya | ||||||
| 1A3 | 2.9 ± 0.4 | 158 ± 29 | 0.018 ± 0.001 | 19.0 ± 4.0 | 251 ± 97 | 0.08 ± 0.01 | ||||
| 1A7 | Low activity | 1.8 ± 0.1 | 68.9 ± 3.8 | 0.026 ± 0.001 | ||||||
| 1A8 | 11.6 ± 1.4 | 101 ± 13 | 0.12 ± 0.01 | 7.1 ± 1.0 | 201 ± 53 | 0.036 ± 0.005 | ||||
| 1A9 | Low activity | 7.2 ± 0.3 | 56.0 ± 3.3 | 0.13 ± 0.01 | ||||||
| 1A10 | 5.7 ± 0.7 | 39.9 ± 3.4 | 0.14 ± 0.005 | 34.2 ± 3.3 | 11.2 ± 0.9 | 3.1 ± 0.2 | ||||
| 2B7 | 3.0 ± 0.4 | 101 ± 17 | 0.030 ± 0.004 | 2.1 ± 0.3 | 120 ± 22 | 0.018 ± 0.001 | ||||
| 2B15 | N.D. | 1.4 ± 0.1 | 32.7 ± 6.4 | 0.044 ± 0.006 | ||||||
| 2B17 |
| N.D. |
| 0.21 ± 0.02 | 43.6 ± 9.3 | 0.005 ± 0.001 | ||||
N.D., not detectable.
↵ a Low activity describes that fact that although some glucuronidation activity was observed for that UGT against a particular TAM metabolite, the level of detection was below sensitivity for kinetic studies.