Table 1.
Transcriptional activity and relative binding affinity of benzothiophene analogs.
|
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|---|---|---|---|---|---|
|
| |||||
| Compounds | X | R | ERE luciferasea
EC50 (nM) |
Efficacy(% E2) |
RBAral b |
| 3 | NA | 0 | 100 ± 14.4 | ||
| 11 | -OH | -H | NA | 0 | 0.6 ± 0.2 |
| 12 | -F | -H | NA | 0 | 0.2 ± 0.1 |
| 14a | -OH |
|
2.6 ± 0.4 | 100 | 3.3 ± 0.2 |
| 14b | -F |
|
61.5 ± 14.4 | 100 | 0.9 ± 0.4 |
| 14c | -Cl |
|
121 ± 19.2 | 100 | 1.2 ± 0.2 |
| 19 | -F |
|
6.2 ± 2.8 | 100 | 32.6 ± 2.3 |
| 21a | -F |
|
436.2 ± 112.1 | 100 | 4.4 ± 1.3 |
| 21b | -F |
|
0.2 ± 0.1 | 100 | 13.8 ± 0.9 |
| 21c | -F |
|
30.6 ± 14.4 | 51 | 0.4 ± 0.1 |
| 21d | -F |
|
717.1 ± 261.6 | 100 | 3.8 ± 1.0 |
| 21e | -F |
|
18.5 ± 9.5 | 100 | 5.1 ± 3.7 |
| 21f | -F |
|
13.9 ± 3.3 | 100 | 14.4 ± 5.7 |
| 21g | -F |
|
1.0 ± 0.1 | 100 | 1.9 ± 0.3 |
| 23 | -F |
|
5.3 ± 1.7 | 65 | 2.1 ± 0.7 |
| 26a | -F |
|
5.2 ± 1.4 | 85 | 0.5 ± 0.1 |
| 26b | -F |
|
58.7 ± 8.6 | 100 | 0.9 ± 0.2 |
| 30a | -F |
|
0.8 ± 0.3 | 60 | 14.2 ± 0.8 |
| 30b | -F |
|
76.1 ± 25.1 | 70 | 0.4 ± 0.1 |
| 30c | -F |
|
36.8 ± 4.4 | 100 | 0.4 ± 0.1 |
| 30d | -F |
|
33.4 ± 2.5 | 100 | 0.4 ± 0.1 |
a
In MCF-7:ws8 cells, estrogenic activity was measured using a luciferase reporter assay and normalized to Ctrl (0%) and E2-1nM (100%). Data show mean ± s.e.m. determined from an average of at least three passages.
b
RBAral measuring reduction in FP caused by displacement of fluorescein-E2 from ER, data are normalized to raloxifene binding at 100% ± s.e.m. NA = no activity.