Avadomide

Cereblon (CRBN) is a substrate receptor of the Cullin 4 RING E3 ubiquitin ligase complex, that promotes the ubiquitination and subsequent degradation of 2 common substrates, transcription factors Alolos and Ikaros. CC-122 is a new chemical entity termed pleiotropic pathway modifier, binds CRBN and induces apoptosis in a broad panel of diffuse large B-cell lymphoma (DLBCL), and stimulated IL-2 production in primary T cells. In vitro, CC-122 induced growth arrest and apoptosis in activated B-cell and germinal center B-cell DLBCL cell lines at concentration ranging in 0.1 – 10 μM. Treatment with 10 μM CC-122 promoted CRBN-Ikaros interaction and subsequent proteasomal degradation of Aiolos and Ikaros in DLBCL cell lines TMD8, OCI-LY10 and Karpase 422³. Treatment with 1 μM CC-122 inhibited cell invasion and migration in hepatocellular carcinoma (HCC) cell lines. In addition, CC-122 significantly reduced TCG-4 J and its target genes SPP1, AXIN2, MMP7, ASPH, CD24, ANXA1, and CAMK2N1⁴. In vivo, treatment with 30 mg/kg once daily for 30 days significantly decreased tumor growth in OCILY10 ABC-DLBCL and WSU-DLCL2 derived xenograft models. Administration of CC-122 at 30 mg/kg once daily for 24h significantly decreased Aiols and IKaros expression in WSU-DLCL2 xenograft transplanted mice³. Oral administration of CC-122 at 30 mg/kg for 40 days reduced growth rate of HAK-1A-J tumors in HCC xenografts model⁴. A phase I Clinical trial study shows that CC-122 might regulate the NK phenotype and its activity due to the reduced accumulation of myeloid derived suppressor cell and eventually decrease the Tregs subsets⁵.

溶解方案(细胞实验)

DMSO 中的溶解度 : 33.33 mg/mL (116.42 mM; 超声助溶; 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)

溶解方案(动物实验)

"方案 一": "请依序添加每种溶剂：10% DMSO 40% PEG300 5% Tween-80 45% SalineSolubility: ≥ 2.5 mg/mL (8.73 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；再向上述体系中加入 50 μL Tween-80，混合均匀；然后再继续加入 450 μL 生理盐水 定容至 1 mL。生理盐水的配制：将 0.9 g 氯化钠，溶解于 ddH₂O 并定容至 100 mL，可以得到澄清透明的生理盐水溶液。"