TABLE 1.
Inhibition of hSULT1E1-catalyed sulfation of estradiol by metabolites of tamoxifen
The sulfation of estradiol was determined using 3.0 ng purified hSULT1E1 in the presence of varied concentrations of inhibitor and either 7.0 nM estradiol (for IC50 values) or 3 nM–10 nM estradiol for determination of the best fit to a kinetic model of inhibition and the kinetic constants for that fit to the model. In the case of TAM-NO, the inconclusive fit to a kinetic model is denoted as N.A. The data are expressed as the means ± S.E. from three independent experiments. Calculation of kcat values was based on 70,252 as the dimeric molecular mass of hSULT1E1.
| Metabolite | IC50 | Inhibition Model | Vmax(app) | Km(app) | kcat/Km | Ki |
|---|---|---|---|---|---|---|
| μM | nmol/min/mg | nM | min−1nM−1 | μM | ||
| Endoxifen | 21 ± 1 | Noncompetitive | 680 ± 237 | 63 ± 25 | 0.76 ± 0.4 | 30 ± 1 |
| N-desTAM | 8.2 ± 0.9 | Mixed | 435 ± 66 | 38 ± 7 | 0.81 ± 0.2 | 10 ± 1 |
| 4-OHTAM | 7.0 ± 1.1 | Noncompetitive | 553 ± 149 | 57 ± 17 | 0.68 ± 0.3 | 38 ± 1 |
| TAM-NO | 18 ± 1 | N.A. |