HBX 41108
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
HBX 41108是USP7的有效抑制剂,IC50值为424 nM [1]。
USP7是泛素特异性蛋白酶,可以除去来自特定蛋白底物的泛素。USP7可以使P53去泛素化,保护p53免于Mdm2介导的降解,参与p53基因的致癌稳定性。
HBX 41108是USP7的非竞争性的可逆抑制剂。HBX 41108以剂量依赖性方式抑制USP7介导的p53去泛素化,IC50值为0.8 μM,对于天冬氨酸、丝氨酸和金属蛋白酶的活性较弱,IC50大于10 μM。在HCT116细胞中,HBX 41108增加p53和p21cip1/waf的水平,这是p53靶基因的产物。在HEK293细胞中,HBX 41108增加聚泛素化形式的p53蛋白,减少Mdm2的水平。在HCT116结肠癌细胞中,HBX 41108以剂量依赖性方式抑制细胞增殖,IC50值为1 μM,同时以剂量依赖性方式诱导细胞凋亡[1]。在COS7细胞中,HBX 41108抑制USP7诱导的PPARγ稳定性,将PPARγ的基础转录活性降低70%[2]。
参考文献:
[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.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 266.64 |
Cas No. | 924296-39-9 |
Formula | C13H3ClN4O |
Solubility | insoluble in H2O; ≥1.83 mg/mL in EtOH with gentle warming and ultrasonic; ≥13.35 mg/mL in DMSO |
Chemical Name | 7-chloro-9-oxo-9H-indeno[1,2-b]pyrazine-2,3-dicarbonitrile |
SDF | Download SDF |
Canonical SMILES | ClC1=CC=C(C2=NC(C#N)=C(C#N)N=C2C3=O)C3=C1 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
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. |