|1-(3-氯-4-甲基苯基)-3-((2-(2,6-二氧哌啶-3-基)-1-氧异吲哚-5-基)甲基)脲|CsnPharm

CAS No.: 1010100-07-8

CC-885 Catalog No. CSN22248

Synonyms: CC-885

CC-885 is a cereblon (CRBN) modulator with potent anti-tumour activity.

规格	价格	促销价格	库存	数量

400-920-2911

sales@csnpharm.cn

tech@csnpharm.cn

加入购物车大规格询价

加入收藏

产品咨询

400-920-2911

sales@csnpharm.cn

tech@csnpharm.cn

纯度 & 质量文件批次:

靶点选择性

生物活性

实验方案

技术信息

生物活性

描述Cereblon（CRBN) is a brain-associated protein with ionic protease activity, which interacts with DNA damage-binding protein-1 (DDB1), Cullin 4 (Cul4A or Cul4B), and regulator of Cullins 1 (RoC1) to form the functional E3 ubiquitin ligase complex(CRBN-CRL4) that performs proteolysis via the ubiquitin-proteasome pathway^[1]. CC-885 is a modulator of cereblon (CRBN). It has potent anti-tumour activity. The effect of CC-885 on cell proliferation in AML cell lines, THLE-2 and human PBMC is more powerful than Lenalidomide and Pomalidomide with IC50s>10 μM. CC-885 is tested in 293T HEK cells stably expressing the CC-885-sensitive or -resistant GSPT1 variants. Acute myeloblatlic leukemia (AML) cell lines, human liver epithelial cell line (THLE-2) and human peripheral blood mononuclear cells (PBMC) are treated with varying concentrations of CC-885, with IC50s of 10×-6-1 μM. To address whether the cereblon-dependent degradation of GSPT1 is responsible for the cytotoxic effects of CC-885, a GSPT1 mutant that retains its normal function, but loses CC-885-dependent cereblon binding, is used to distinguish the role of GSPT1 from that of other substrates. Overexpression of a resistant variant GSPT1Δ(1–138)/(G575N) completely abrogate the CC-885-induced anti-proliferation. Whereas overexpression of a CC-885-sensitive variant GSPT1Δ(1-138) only confer partial protection. Similar results are obtained in AML cell lines^[2]. CC-885 can synergistically inhibit NSCLC with volasertib both in vitro and in vivo. This synergistic effect overcomes volasertib resistance caused by PLK1 mutations and is compromised in CRBN-or p97-depleted cells. Mechanistically, CC-885 selectively promotes CRBN- and p97-dependent PLK1 ubiquitination and degradation, thereby enhancing the sensitivity of NSCLC to volasertib^[3].
参考文献

[1] Wen-Jing Fan,et al. Molecular Mechanism of CRBN in the Activity of Lenalidomid eagainst Myeloma—Review. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2018. 26(4), 1240-1243.
[2] Mary E. Matyskiela, et al. A novel cereblon modulator recruits GSPT1 to the CRL4CRBN ubiquitin ligase. Nature. 2016. 535(7611), 252-7.
[3] Lifeng Li,et al. A Cereblon Modulator CC-885 Induces CRBN- and p97-Dependent PLK1 Degradation and Synergizes with Volasertib to Suppress Lung Cancer. Mol Ther Oncolytics. 2020. 18, 215-225.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.2682 mL
- 11.3410 mL
- 22.6819 mL
- 5 mM
- 0.4536 mL
- 2.2682 mL
- 4.5364 mL
- 10 mM
- 0.2268 mL
- 1.1341 mL
- 2.2682 mL

技术信息

CAS号

1010100-07-8

储存条件

粉末: Inert atmosphere,Room Temperature

液体: -20°C:3-6 月 -80°C:12月

分子式

C22H21ClN4O4

运输

蓝冰

分子量

440.88

别名

CC-885

溶解度

DMSO	65.5 mg/mL (148.6 mM) warming

动物实验配方

大规格询价

号为必填项

姓名: 邮箱: 手机号:

留言:

提交

CC-885 Catalog No. CSN22248

靶点选择性

请登录您的专属账户

确认信息