| References: |
Lenalidomide and pomalidomide, targeting cereblon, are immunomodulatory drugs that are clinically effective in the treatment of cancer, including newly diagnosed and relapsed multiple myeloma. Iberdomide contains a glutarimide ring that binds in the try-tryptophan pocket of cereblon and an isoindolinone ring that can interact with both cereblon and substrates. Treatment with Iberdomide results in the loss of Ikaros and Aiolos protein levels with EC50s of 1 nM and 0.5 nM.Iberdomide (CC-220) is currently in phase 2 clinical trials for the treatment of systematic lupus erythematosus (SLE) and phase 1b/2a clinical trials for relapsed and refractory multiple myeloma (MM).A potent, next-generation modulator of cereblon E3 ubiquitin ligase with IC50 of 60 nM; exhibits significantly higher affinity than lenalidomide and pomalidomide (IC50=1.5 and 1.2 uM, respectively); reduces and degrades Aiolos and Ikaros protein levels (EC50=1 nM and 0.5 nM, respectively) and BAFF- and CD40L-induced proliferation, plasmablast differentiation, and IgG secretion in cellular degradation assay. |
