Kinase experiment:

Iberdomide is dissolved in DMSO. In the assay, 60 nM 6Xhis-tagged CRBN-DDB1 is combined with 30 nM cy5-conjugated cereblon modulator and 3 nM LanthaScreen Eu-anti-His Tag antibody in 20 mM HEPES pH 7, 150 mM NaCl, 0.005% Tween-20 assay buffer. FRET is observed by exciting at 340 nm and monitoring emission at 615 nm and 665 nm, and FRET efficiency is determined by the ratio of FRET to non-FRET emission. Competing cereblon modulating compound (Iberdomide) or DMSO carrier is titrated and incubated for 10 min before scanning[1].

Iberdomide (CC-220) is a cereblon modulator with an IC50 of 60 nM.

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 [1].

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)[1].

References:
[1]. Matyskiela ME, et al. A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos. J Med Chem. 2017 Apr 20.