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Chemical Structure| 1015474-32-4 同义名 : CC-122
CAS号 : 1015474-32-4
货号 : A128261
分子式 : C14H14N4O3
纯度 : 99%+
分子量 : 286.286
MDL号 : MFCD29919294
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 35 mg/mL(122.26 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
描述 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 422[3]. 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 CAMK2N1[4]. 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 mice[3]. Oral administration of CC-122 at 30 mg/kg for 40 days reduced growth rate of HAK-1A-J tumors in HCC xenografts model[4]. 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 subsets[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.49mL

0.70mL

0.35mL

17.47mL

3.49mL

1.75mL

34.93mL

6.99mL

3.49mL
参考文献

[1]Hagner PR, Man HW, et al. CC-122, a pleiotropic pathway modifier, mimics an interferon response and has antitumor activity in DLBCL. Blood. 2015 Aug 6;126(6):779-89.

[2]Jacques V, Czarnik AW, et al. Differentiation of antiinflammatory and antitumorigenic properties of stabilized enantiomers of thalidomide analogs. Proc Natl Acad Sci U S A. 2015 Mar 24;112(12):E1471-9.

[3]Hagner PR, Man HW, Fontanillo C, Wang M, Couto S, Breider M, Bjorklund C, Havens CG, Lu G, Rychak E, Raymon H, Narla RK, Barnes L, Khambatta G, Chiu H, Kosek J, Kang J, Amantangelo MD, Waldman M, Lopez-Girona A, Cai T, Pourdehnad M, Trotter M, Daniel TO, Schafer PH, Klippel A, Thakurta A, Chopra R, Gandhi AK. CC-122, a pleiotropic pathway modifier, mimics an interferon response and has antitumor activity in DLBCL. Blood. 2015 Aug 6;126(6):779-89.

[4]Tomimaru Y, Aihara A, Wands JR, Aloman C, Kim M. A Novel Drug, CC-122, Inhibits Tumor Growth in Hepatocellular Carcinoma through Downregulation of an Oncogenic TCF-4 Isoform. Transl Oncol. 2019 Oct;12(10):1345-1356.

[5]Cubillos-Zapata C, Cordoba R, Avendaño-Ortiz J, Arribas-Jiménez C, Hernández-Jiménez E, Toledano V, Villaescusa T, Moreno V, López-Collazo E. CC-122 immunomodulatory effects in refractory patients with diffuse large B-cell lymphoma. Oncoimmunology. 2016 Sep 16;5(12):e1231290.