Table 1.
Comparison of the binding affinities of the cereblon ligands lenalidomide (1), thalidomide (4), and pomalidomide (8)
| Assay condition | Lenalidomide (1) |
Thalidomide (4) |
Pomalidomide (8) |
|||
|---|---|---|---|---|---|---|
| IC50 | Ki | IC50 | Ki | IC50 | Ki | |
| TR-FRET assay with BODIPY FL Thalidomide (10) | 8.9 nM | 4.2 nM | 22.4 nM | 10.6 nM | 6.4 nM | 3.0 nM |
| FP assay with Cy5-conjugated thalidomide (7)10 | 296.9 nM | 177.8 nM | 404.6 nM | 249.2 nM | 264.8 nM > 41- foldb |
156.6 nM |
| TR-FRET assay with Cy5-conjugated cereblon modulator (compound 7) (9)11 | 1.5 μM | NAa | NA | NA | 1.2 μM >187-foldb |
NA |
a
NA: not available.
b
Fold change sensitivity was calculated by dividing the IC50 value from the previously reported assay by the IC50 value of 6.4 nM obtained from the BODIPY FL Thalidomide (10)-mediated TR-FRET binding assay.