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

Avadomide是针对DLBCL的新型化合物，具有抗肿瘤和免疫调节活性。在DLBCL细胞系中，它通过结合CRBN并诱导Aiolos和Ikaros的降解或短发夹RNA介导的敲除来发挥作用，这与IFN（干扰素）刺激基因的增加转录相关，而这一过程是独立于IFN-α、-β和-γ的产生和/或分泌的，最终导致在活化的B细胞（ABC）和生发中心B细胞DLBCL细胞系中诱发凋亡。CRBN是Avadomide的分子靶点，Avadomide与CRBN的结合吸引了Aiolos/Ikaros到CRL4CRBN，并且E3连接酶的酶活性对于Aiolos和Ikaros的泛素化以及通过Avadomide引起的它们的蛋白酶体降解是必需的。Avadomide诱导IFN调节的蛋白质表达，并且它对IFN途径的影响是独立于自分泌型I和II IFN的分泌和信号传导的[1]。

Avadomide在ABC-和GCB-DLBCL细胞系建立的异种移植模型中减缓肿瘤生长，并在原代T细胞中刺激IL-2的产生。此外，在单臂Avadomide临床试验中，接触Avadomide使每位患者的Aiolos和Ikaros表达水平下降了25%至50%，证明这两种蛋白作为Avadomide药效学标志物的有效性[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)