Table 1.
Binding affinity and potency of CO23 analogues
|
Kd and EC50 values (nM) |
||||||
|---|---|---|---|---|---|---|
|
Binding affinity (Kd)a |
Transactivation in U2OS cells (EC50)b |
Transactivation in HeLa cells (EC50)b |
||||
| Compound | TRα | TRβ | TRα | TRβ | TRα | TRβ |
| T3c | 0.058 | 0.081 | 2.4 ± 0.4 | 11 ± 2 | 2.4 ± 0.5 | 2.4 ± 0.5 |
| CO23c | 1.2 ± 0.2 | 1.7± 0.3 | 34 ± 4 | 390 ± 3 | 11 ± 1 | 58 ± 1 |
| CO24 | 17 ± 1 | 18.4 ± 1 | 128 ± 5 | 421 ± 3 | 8.4 ± 3 | 32 ± 3 |
| CO26 | 82 ± 21 | 119 ± 30 | 870 ± 160 | 8000 ± 1800 | 42 ± 6 | 265 ± 10 |
| CO27 | 42 ± 13 | 53 ± 17 | 146 ± 28 | 4000 ± 1000 | 27 ± 6 | 180 ± 30 |
| CO28 | 15 ± 6 | 18 ± 2 | 87 ± 14 | 1400 ± 170 | 10 ± 1 | 27 ± 6 |
| CO29 | 25 ± 7 | 49 ± 5 | 145 ± 10 | 2000 ± 290 | 39 ± 4 | 100 ± 14 |
| CO30 | 1700 ± 10 | 2000 ± 360 | >20000d | >20000d | >10000d | >10000d |
| CO31 | 24 ± 3 | 36 ± 1 | 105 ± 8 | 2000 ± 170 | 21 ± 3 | 216 ± 80 |
| CO32 | 43 ± 6 | 68 ± 10 | 206 ± 41 | 5200 ± 670 | 44 ± 1 | 530 ± 170 |
a
Determined by means of an 125I-T3 competitive binding assay and data is reported as the mean Kd ± standard error of the mean, n=3.
b
Determined through use of a TRE-driven dual-luciferase reporter assay in U2OS or HeLa cells and the data is reported as the mean EC50 value ± standard error of the mean, n=3.
c
See reference 36.
d
Dose-response curves generated using CO30 in transactivation assays did not plateau, and hence the EC50 value is an approximated value based on extrapolation.