切换导航

P005091

现货
Catalog No.
A3023
泛素特异性蛋白酶7(USP7)抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 850.00
现货
10mg
¥ 800.00
现货
50mg
¥ 2,500.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

P005091 is a selective, potent inhibitor of USP7 deubiquitylating activity, which is demonstrated to downregulate claspin and phosphorylation of the DNA checkpoint kinase Chk1, and to synergize with genotoxic agents. USP7, known as herpes-associated-ubiquitin-specificprotease (HAUSP), is a deubiquitylating enzyme that regulates the levels of the oncoprotein HDM2 and its substrate, the tumor suppressor p53. P005091 accelerated the degradation of HDM2, while analogs of the compound induced dose- and time-dependent increases in the protein levels of p53 and p21.What’s more,P005091 induced apoptosis in numerous cancer cell lines, including both p53+/+ and p53-mutant cancer cell lines.

Reference

Jeffrey G Marblestone. Ubiquitin Drug Discovery & Diagnostics 2009 – First Annual Conference. IDrugs. 2009; 12(12):750 – 753.

文献引用

1. Lee MJ, Miller Z, et al. "H727 cells are inherently resistant to the proteasome inhibitor carfilzomib, yet require proteasome activity for cell survival and growth." Sci Rep. 2019 Mar 11;9(1):4089. PMID:30858500

Chemical Properties

Physical AppearanceA solid
StorageStore at 4°C
M.Wt348.22
Cas No.882257-11-6
FormulaC12H7Cl2NO3S2
SynonymsP005091,P5091
Solubility≥17.4 mg/mL in DMSO, <2.83 mg/mL in EtOH, <2.72 mg/mL in H2O
Chemical Name1-[5-(2,3-dichlorophenyl)sulfanyl-4-nitrothiophen-2-yl]ethanone
SDFDownload SDF
Canonical SMILESCC(=O)C1=CC(=C(S1)SC2=C(C(=CC=C2)Cl)Cl)[N+](=O)[O-]
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]:

细胞系

NCI-60人肿瘤细胞系.

溶解方法

该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月

反应条件

生长抑制:48小时。细胞毒性:72小时。溶解于100%(v/v)DMSO中,最终的最大测试浓度为400倍,在使用前冷冻保存。

实验结果

在HL-60(TB)细胞系中,P005091对生长抑制的GI50值为1.82 μM,并表现出广泛的生长抑制。在HCT-116细胞中,P005091显示出细胞毒性,EC50值为9.21 μM。

动物实验[1]:

动物模型

人多发性骨髓瘤肿瘤细胞皮下接种的重度联合免疫缺陷(SCID)小鼠。

剂量

10 mg/kg;静脉内每周两次,持续三周。

实验结果

在SCID小鼠中,P5091显著抑制人浆细胞瘤生长并增强存活。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Cao P, Weinstock J, Kingsbury WD, et al. Anti-neoplastic compounds, compositions and methods. Patent: US 8680139 B2, 2009.

生物活性

描述 P5091(P005091)是一种选择性的和有效的泛素特异性蛋白酶7(USP7,ubiquitin-specific protease 7)抑制剂,EC50值为4.2 μM,与对USP47的作用相似。
靶点            
IC50 4.2 μM (EC50)          

质量控制

化学结构

P005091

相关生物数据

P5091
HEK293T cells were treated with DMSO or P5091; crude cell extracts were labeled with indicated UbVME probe, followed by immunoblotting (IB) with indicated antibodies.

相关生物数据

P005091