The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.
Proposed Mechanism of Action
Ikaros and Aiolos (encoded by the genes IKZF1 and IKZF3, respectively) are substrates of the cullin ring ligase 4 (CRL4CRBN) E3 ubiquitin ligase complex.1 They are members of the Ikaros family of zinc-finger transcription factors and are responsible for lymphocyte differentiation and B-cell development.2,3
Iberdomide is a cereblon (CRBN) E3 ligase modulator. CRBN is the target protein receptor on CRL4CRBN. The exact mechanism by which iberdomide exerts is therapeutic action is unknown. In preclinical studies, iberdomide was shown to redirect CRBN to induce ubiquitination and subsequent proteasomal degradation of target proteins, including Ikaros and Aiolos.2,3
Iberdomide (CC-220) Proposed Mechanism of Action

AutoAbs, autoantibodies CRBN, cereblon; CRL4, cullin ring ligase 4; DC, dendritic cell; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; IgG, immunoglobulin G; IgM, immunoglobulin M; IL, interleukin; TNF, tumor necrosis factor
Iberdomide (CC-220) is a cereblon E3 ligase modulator that can induce degradation of transcription factors Ikaros and Aiolos2, 3
iberdomide (CC-220) by Disease State
iberdomide (CC-220) in Systemic Lupus Erythematosus
Phase 1
Systemic Lupus Erythematosus
View Trials Investigating iberdomide (CC-220) in Systemic Lupus Erythematosus
View Rationale for Clinical Development
Rationale for Clinical Development
Systemic lupus erythematosus (SLE) is a multisystem, chronic, autoimmune disorder in which different body systems are affected by inflammation.4,5 Genome-wide association studies have shown that polymorphisms in IKZF1 and IKZF3 correlated with an increased risk for developing SLE,2,3,6,7 and Ikaros and Aiolos were overexpressed in the peripheral blood.2,3 Hence, targeting Ikaros and Aiolos expression with iberdomide may have the potential to mitigate aberrant activation of B cells that result in the production of pathogenic autoantibodies associated with SLE.2,8,9