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Iberdomide

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Chemical Structure| 1323403-33-3 同义名 : CC-220
CAS号 : 1323403-33-3
货号 : A247784
分子式 : C25H27N3O5
纯度 : 99%+
分子量 : 449.499
MDL号 : MFCD31382133
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(266.96 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • CRBN

    cereblon, IC50:60 nM
描述 Ubiquitin is a protein modifier that regulates many essential cellular processes. The E1 enzyme activates the C-terminal carboxylate of UB to launch its transfer through the E1-E2-E3 cascade onto target proteins to intiate the modification of the protein[2]. CC-220 is a cereblon modulator which achieves greater substrate degradation via tighter binding to the cereblon E3 ligase with IC50 value of 60nM[1]. CC-220, a representative lenalidomide analog, could display significant anti-proliferative and pro-apoptotic activity on sensitive and resistant MM cell lines. In addition, CC-220-stimulated immunomodulatory activity could induce PBMC mediated tumoricidal effect regardless of the level of CRBN expression, leading to greater interleukin-2 secretion and granzyme-b degranulation in immune cells. In vitro, CC-220 exhibited anti-proliferative activity against the MM.1S and Mino cell lines with IC50 values of 13nM and 111.6nM, respectively[3]. Treatment of B cells and T cells with 10nM CC-220 for 24h resulted in a significant decrease in the protein levels of Ikaros and Ailos[4]. In vivo, following oral administration at dosages of 20mg/kg could achieve a Cmax of 2061ng/mL at 0.14h, and had a relative oral bioavailability value of 22.8% in female balb/c mice. Oral administered CC-220 at dosages of 60mg/kg could delay RPMI 8826 tumor growth in the female CB-17 SCID mice[3]. Clinical studies have shown that CC-220 at the dose range of 0.3-6mg in healthy volunteers decreased intracellular Ailos, decreased absolute CD19+ B cells, increased IL-2 and decreased IL-1β production ex vivo[4].
作用机制 CC-220 binds to the protein cereblon, directing the CRL4-CRBN E3 ligase toward the transcription factors Ikaros and Aiolos to cause their ubiquitination and degradation[1].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.22mL

0.44mL

0.22mL

11.12mL

2.22mL

1.11mL

22.25mL

4.45mL

2.22mL
参考文献

[1]Matyskiela M, Zhang W, Man H, et al. A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos. Journal of Medicinal Chemistry, 2017, 61(2): 535-542

[2]Zhao B, Bhuripanyo K, Schneider J R, et al. Specificity of the E1-E2-E3 enzymatic cascade for ubiquitin C-terminal sequences identified by phage display. ACS Chemical Biology, 2012, 7(12): 2027-2035

[3]Xiao D, Wang Y, Hu X, et al. Design, synthesis and biological evaluation of the thioether-containing lenalidomide analogs with anti-proliferative activities. European Journal of Medicinal Chemistry, 2019: 419-430

[4]Schafer P H, Ye Y, Wu L, et al. Cereblon modulator iberdomide induces degradation of the transcription factors Ikaros and Aiolos: immunomodulation in healthy volunteers and relevance to systemic lupus erythematosus. Annals of the Rheumatic Diseases, 2018, 77(10): 1516-1523.