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HBX 41108

现货
Catalog No.
B5550
泛素特异性蛋白酶(USP)7抑制剂
组合的产品项目
规格价格库存 数量
10mg
¥ 1,550.00
现货

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Background

HBX 41108 is a potent inhibitor of USP7 with IC50 value of 424 nM [1].

Ubiquitin-specific-processing protease 7 (USP7) is a ubiquitin specific protease and removes ubiquitin from specific protein substrates. USP7 can deubiquitinate p53, protecting p53 from Mdm2-mediated degradation and involving the oncogenic stabilization of p53.

HBX 41108 is an uncompetitive and reversible USP7 inhibitor. HBX 41108 inhibited USP7-mediated p53 deubiquitination with IC50 value of 0.8 μM in a dose-dependent way and was only weakly active against the aspartic, serine and metalloproteases tested with IC50 > 10 μM. In HCT116 cells, HBX 41108 increased the levels of p53 and p21cip1/waf, which was the product of p53 target genes. In HEK293 cells, HBX 41108 increased the level of polyubiquitinated forms of p53 and reduced Mdm2 levels. In HCT116 colon cancer cells, HBX 41108 inhibited cell proliferation with IC50 value of 1 μM in a dose-dependent way and induced apoptosis in a dose-dependent manner [1]. In COS7 cells, HBX 41108 inhibited PPARγ stability induced by USP7 and decreased the basal transcriptional activity of PPARγ by 70% [2].

References:
[1].  Colland F, Formstecher E, Jacq X, et al. Small-molecule inhibitor of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells. Mol Cancer Ther, 2009, 8(8): 2286-2295.
[2].  Lee KW, Cho JG, Kim CM, et al. Herpesvirus-associated Ubiquitin-specific Protease (HAUSP) Modulates Peroxisome Proliferator-activated Receptor γ (PPARγ) Stability through Its Deubiquitinating Activity. J Biol Chem, 2013, 288(46): 32886-32896.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt266.64
Cas No.924296-39-9
FormulaC13H3ClN4O
Solubility≥13.35mg/mL in DMSO
Chemical Name7-chloro-9-oxo-9H-indeno[1,2-b]pyrazine-2,3-dicarbonitrile
SDFDownload SDF
Canonical SMILESClC1=CC=C(C2=NC(C#N)=C(C#N)N=C2C3=O)C3=C1
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1, 2]:

细胞系

HCT116结肠癌细胞

溶解方法

该化合物在DMSO中的溶解度大于10 mM。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

24 h

应用

在HCT116结肠癌细胞中,用不同剂量的HBX 41,108(1、3和10 μmol/L)处理24小时以非基因毒性方式增加p53水平。在USP7转染的HEK293细胞中,HBX 41,108抑制USP7活性。HBX 41,108(0.1-10 μM,24h)抑制HCT116癌细胞生长并诱导凋亡性细胞死亡。在p53野生型和无效的同基因癌细胞系中,HBX 41,108诱导p53依赖性细胞凋亡。在COS7细胞中,HBX 41,108抑制了USP7诱导的PPARγ稳定,将PPARγ的基底转录活性降低了70%。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Colland F, Formstecher E, Jacq X, et al. Small-molecule inhibitor of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells. Mol Cancer Ther, 2009, 8(8): 2286-2295.

[2]. Lee KW, Cho JG, Kim CM, et al. Herpesvirus-associated Ubiquitin-specific Protease (HAUSP) Modulates Peroxisome Proliferator-activated Receptor γ (PPARγ) Stability through Its Deubiquitinating Activity. J Biol Chem, 2013, 288(46): 32886-32896.

质量控制

质量控制和MSDS

批次:

化学结构

HBX 41108