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The small-molecule drugs thalidomide, lenalidomide, and pomalidomide bind to the protein cereblon (CRBN), which activates the enzymatic activity of the CRBN E3 ubiquitin ligase complex. The transcription factors lkaros (IKZF1) and Aiolos (IKZF3) are modified with ubiquitin (Ub) molecules, targeting them for proteolysis. This alters the function ofT cells and B cells, with a toxic outcome for multiple myeloma cells.
