Table 1.
In vitro properties of ligands.
| Receptor-binding affinity | LXRα transactivation | LXRβ transactivation | ||||
|---|---|---|---|---|---|---|
| pKi LXRα | pKi LXRβ | pEC50 | Agonist efficacy, % | pEC50 | Agonist efficacy, % | |
| AZ1 | 7.04 | 8.6 | 6.96 | 102 | 7.51 (0, n = 2) | 76.0 (0, n = 2) |
| AZ2 | 7.04 (0.16, n = 7) | 8.43 (0.07, n = 7) | 7.11 (0.12, n = 7) | 111.4 (10.7, n = 7) | 8.06 (0.13, n = 7) | 97.3 (12.2, n = 7) |
| AZ3 | 6.3 (0.08, n = 3) | 7.76 (0.15, n = 3) | 6.09 (0.37, n = 4) | 142.5 (37.7, n = 4) | 7.12 (0.34, n = 4) | 94.3 (18.0, n = 4) |
| AZ4 | 6.45 (0.48, n = 2) | 7.48 (0.36, n = 2) | 6.37 (0.03, n = 2) | 103.0 (9.9, n = 2) | 6.83 (0.13, n = 4) | 110.0 (0, n = 4) |
| AZ5 | 5.67 (0.28, n = 2) | 7.11 (0.19, n = 2) | 5.97 (0.23, n = 2) | 60.5 (21.9, n = 2) | 7.01 (0.02, n = 2) | 66.5 (10.6, n = 2) |
| AZ6 | 5.8 (0.25, n = 5) | 6.79 (0.29, n = 5) | 5.91 (0.23, n = 6) | 87.8 (5.0, n = 6) | 6.21 (0.15, n = 7) | 95.3 (2.9, n = 7) |
| AZ7 | 5.97 (0.14, n = 10) | 6.98 (0.19, n = 10) | 5.96 (0.12, n = 10) | 85.3 (8.7, n = 10) | 6.27 (0.05, n = 11) | 104.5 (13.5, n = 11) |
| AZ8 | 6.71 | 7.32 | 5.76 (0.08, n = 2) | 91.5 (10.6, n = 2) | 5.89 (0.07, n = 3) | 102.0 (6.9, n = 3) |
| AZ9 | 6.24 | 7.09 | 6.33 (0.14, n = 3) | 90.3 (9.0, n = 3) | 6.55 (0.11, n = 4) | 99.0 (1.4, n = 4) |
| AZ876 | 8.22 (0.25, n = 3) | 7.98 (0.09, n = 3) | 8.25 (0.21, n = 4) | 101.0 (17.1, n = 3) | 7.15 (0.11, n = 5) | 107.4 (14.1, n = 5) |
| T0-091317 | 7.15 | 7.58 | 7.4 (0.12, n = 71) | 100.8 (7.4, n = 4) | 7.19 (0.13, n = 67) | 95.5 (6.4, n = 2) |
| WAY-254011 | 7.34 | 7.95 | 6.86 | 85 | 7.23 | 69.0 (0, n = 2) |
| F1 | 7.99 | 7.44 | 6.25 | 84 | 5.41 | 105 |
| GW3965 | 6.8 (0.24, n = 5) | 7.62 (0.29, n = 5) | 5.96 (0.18, n = 15) | 93.5 (15.7, n = 12) | 6.46 (0.18, n = 22) | 77.1 (6.2, n = 19) |
| LXR-623 | 6.31 (0.19, n = 4) | 7.02 (0.08, n = 4) | 5.59 (0.09, n = 4) | 102.3 (18.7, n = 4) | 5.73 (0.06, n = 4) | 94.3 (24.3, n = 4) |
| BMS-852927 | 7.69 (0.13, n = 3) | 8.58 (0.15, n = 3) | <4.7 | NA | <4.7 | NA |
| 24,25EC | 6.56 (0.2, n = 2) | 6.88 (0.15, n = 2) | <4.3 | NA | <4.3 | NA |
pEC50 values describe the negative logarithm of the concentrations at which tested compounds reach their half-maximal signal. Agonist efficacy describes the maximal achieved activation compared with a reference full agonist compound. The numbers in parentheses are the standard deviations and number of independent experiments. Values without standard deviations were obtained in experiments run once. Values obtained in each individual experiment are derived from the average of three (binding affinity) or four (transactivation) measurements