Iberdomide | Cereblon modulator/Molecular glue

Iberdomide (1323403-33-3) is a modulator of the cullin ring ligase 4-cereblon E3 ubiquitin ligase complex with higher affinity (IC₅₀ = 60 nM) than lenalidomide and pomalidomide leading to more potent degradation of Ikaros (IKZF1; EC₅₀ = 1 nM)) and Aiolos (IKZF3; EC₅₀ = 0.5 nM).¹ It is more specific for the cereblon complex and does not degrade GSPT1 or CK1α. It displays antitumor and immunostimulatory activity in lenalidomide- and pomalidomide-resistant multiple myeloma cells.² Iberdomide has also shown efficacy in treating the autoimmune disease cutaneous lupus erythematosus (CLE).³ It was also shown to act as an HIV-1 latency reversal agent in in CD4+ T-cells.⁴

References/Citations:

1. Matyskiela et al. (2018), A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos; J. Med. Chem., 61 535
2. Bjorkland et al. (2020), 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; Leukemia, 34 1197
3. Sprow et al. (2022), Emerging Therapies in Cutaneous Lupus Erythematosus; Front. Med. (Lausanne), 9 968323
4. Ne et al. (2022), Catchet-MS identifies IKZF1-targeting thalidomide analogues as novel HIV-1 latency reversal agents; Nucleic Acids Res., 50 5577