Figure 1.

The capacity to degrade IKZF1 correlates with the anti-myeloma potency of THAL, LEN and POM. (A and B) 8226 and H929 cells, which stably express IKZF-luciferase fusion proteins were treated with the indicated dose of LEN, POM and THAL (see table below graph) for 24 h and luciferase activity in drug-exposed cell-lines were measured. The relative ability of drug to degrade IKZF1 is dose dependent and potency demonstrates THAL<LEN<POM. (C) 14 myeloma cell lines with variable sensitivity to LEN were infected with adenovirus expressing IKZF1-luciferase fusion proteins. Cells were treated with vehicle (DMSO) or LEN for 5 h and luciferase activities were measured. Cell lines are ranked from most LEN resistant on the left to most LEN sensitive on the right and luciferase percent degradation in response to LEN is shown in the bars. Data generated from each cell line were normalized to vehicle-treated control. Overall ability to degrade IKZF1 strongly correlates with drug responsiveness.