Table 1.
Activity of ER ligands
| Compound | Receptor affinity |
ER-dependent cell assays |
||||
|---|---|---|---|---|---|---|
| Ki α, nM | MCF-7 (IC50), nM | Ishikawa (IC50), nM | Inhibition, % | Relative (EC50), nM | Stimulation, % | |
| 4-hydroxytamoxifen | 0.20 (0.17, n = 4) | 0.63 (0.06, n = 2) | 340.95 (706, n = 295) | 55.8 (20.8, n = 417) | 2.45 (6.6, n = 404) | 131.3 (33.3, n = 407) |
| Lasofoxifene | 0.34 (0.18, n = 5) | 0.68 (0.01, n = 2) | 6.97 (1.9, n = 6) | 87.5 (8.5, n = 6) | 0.22 (0.08, n = 6) | 65.96 (17.5, n = 6) |
| LY165176 | 0.21 (0.08, n = 6) | 6.1 (n = 1) | 233.6 (123.5, n = 2) | 61.5 (6.3, n = 2) | 0.28 (0.25, n = 2) | 128.7 (48.6, n = 2) |
| LY156681 | 0.44 (0.05, n = 3) | 2.89 (1.7, n = 3) | NA | 33.85 (3.5, n = 4) | 4.67 (0.89, n = 4) | 164.4 (30, n = 4) |
| Raloxifene (38) | 0.37 (0.09, n = 3) | 0.37 (0.03, n = 2) | 4.32 (1.69, n = 8) | 96.8 (7.0, n = 8) | NA | 28.6 (8.5, n = 8) |
| Bazedoxifene | 0.65 (0.17, n = 3) | 0.47 (n = 1) | 3.6 (1.8, n = 274) | 99.1 (8.7, n = 276) | NA | 7.6 (8.8, n = 267) |
| LY117018 | 0.32 (0.07, n = 3) | 1.05 (0.55, n = 34) | 3.42 (0.25, n = 2) | 83.3 (2.1, n = 2) | 0.39 (0.19, n = 2) | 37.2 (17.6, n = 2) |
| Estradiol | 0.16 (0.07, n = 380) | NA | NA | NA | 0.81 (1.13, n = 383) | 581.2 (273, n = 383) |
| DES | 0.09 (0.05, n = 3) | NA | NA | NA | 0.11 (0.01, n = 2) | 410.7 (136.4, n = 2) |
| LY88074 | 0.67 (0.25, n = 3) | NA | NA | 20.1 (7.4, n = 2) | 105.7 (40.2, n = 2) | 179.8 (34.5, n = 2) |
| ICI182780 | 3.0 (0.23, n = 4) | 0.29 (0.20, n = 3) | 0.58 (0.5, n = 383) | 101.18 (7.06, n = 386) | NA | 7.8 (10.8, n = 375) |
MCF-7 values are half-maximal inhibition concentrations (nM) that block stimulation by 10 pM estradiol. Ishikawa agonism is the percentage increase in alkaline phosphatase compared with tamoxifen, whereas Ishikawa antagonism is the efficacy (%) of blocking 2 nM estradiol response, and the IC50 values are the compound concentration needed to block 50% of this estradiol stimulation. The numbers in parentheses are the SDs. Values without SD were run once.