Abstract
Iberdomide (CC-220) is a potent cereblon E3 ligase modulator with antitumor and immunostimulatory activities in lenalidomide- and pomalidomide-resistant multiple myeloma cells with dysregulated CRBN
Highlights
1234567890();,: 1234567890();,: To the Editor: Immunomodulatory compounds, IMiDs® lenalidomide and pomalidomide mediate their anti-myeloma activities via cereblon, a component of the Cul4ACRBN E3 ligase complex [1, 2]
In a panel of MM cell lines across a range of concentrations, iberdomide had pronounced antiproliferative effects (Fig. S1B) compared to lenalidomide and pomalidomide measured by a ‘sensitivity shift’ of the relative percentage of AUC reduction (Supplementary Methods) (Fig. S1C)
Shown here is the representative of three independent experiments apoptosis at 11%, 77%, and 89% respectively, the combination of iberdomide/bortezomib increased the apoptotic fraction to 95%, compared to pomalidomide/bortezomib at 87% (Fig. S2C)
Summary
1234567890();,: 1234567890();,: To the Editor: Immunomodulatory compounds, IMiDs® lenalidomide and pomalidomide mediate their anti-myeloma activities via cereblon, a component of the Cul4ACRBN E3 ligase complex [1, 2]. We observed order of antiproliferative activity of iberdomide > pomalidomide > lenalidomide in matched lenalidomide-sensitive (H929) and an acquired lenalidomide-resistant (H929/LR) cell line (Fig. S1A). In a panel of MM cell lines across a range of concentrations, iberdomide had pronounced antiproliferative effects (Fig. S1B) compared to lenalidomide and pomalidomide measured by a ‘sensitivity shift’ of the relative percentage of AUC reduction (Supplementary Methods) (Fig. S1C).
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