Avadomide (CC 122) is an orally available pleiotropic pathway modulator with potential antineoplastic activity.

Avadomide is a novel agent for DLBCL with antitumor and immunomodulatory activity. In DLBCL cell lines, It binds CRBN and induces degradation or short hairpin RNA-mediated knockdown of Aiolos and Ikaros which correlates with increased transcription of interferon (IFN)-stimulated genes independent of IFN-α, -β, and -γ production and/or secretion and results in apoptosis in both activated B-cell (ABC) and germinal center B-cell DLBCL cell lines. CRBN is the molecular target of Avadomide, Avadomide binding to CRBN recruits Aiolos/Ikaros to CRL4CRBN, and E3 ligase enzymatic activity is necessary for ubiquitination of Aiolos and Ikaros and thus their proteasomal degradation induced by Avadomide. Avadomide induces IFN-regulated proteins and its mediated effects on the IFN pathway is independent of autocrine type I and II IFN secretion and signaling[1].

Avadomide reduces tumor growth in xenograft models established from ABC- and GCB-DLBCL cell lines, and stimulates IL-2 production in primary T cells. Also, in a single-arm Avadomide Clinicalal trial, exposure to Avadomide reduced expression levels of Aiolos and Ikaros in each patient by 25% to 50% demonstrating the utility of these 2 proteins as pharmacodynamic markers of Avadomide[1].

Diffuse Large B-Cell Lymphoma are cultured in RPMI-1640 containing 10-20% fetal bovine serum, 1% Penicillin/Streptomycin and 1 mM sodium pyruvate. 2×104 cells are plated per well in media containing either DMSO or various concentrations of CC-122. Cells are cultured for 5 days at 37 degrees Celsius after which tritiated thymidine is added to the cell culture for the final 6 hours. Cells are subsequently harvested onto filter plates. After the plates have dried, scintillation fluid is added to the plates and read on a Top-count reader(Only for Reference)