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NVP-BEP800

现货
Catalog No.
A4064
全合成的HSP90β口服抑制剂
组合的产品项目
规格价格库存 数量
5mg
¥ 1,100.00
现货
10mg
¥ 1,900.00
现货
25mg
¥ 4,100.00
现货
100mg
¥ 9,600.00
现货

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Background

NVP-BEP800 is a fully synthetic, orally bioavailable inhibitor of Hsp90 with IC50 value of 58nM [1].

NVP-BEP800 binds to the N-terminal ATP-binding pocket of Hsp90. In a competitive binding fluorescence polarization assay, NVP-BEP800 inhibits Hsp90β with IC50 value of 58nM. And to other 20 protein kinases, NVP-BEP800 shows a IC50 of >10μM. In BT-474 cells and A375 cells, NVP-BEP800 causes the Hsp90-p23 dissociation and client protein degradation (ErbB2) as well as the reduction of client protein phosphorylation (phospho-Akt). Degradation of these oncogenic client proteins results in tumor cell growth arrest and death. NVP-BEP800 inhibits proliferation of tumor cells with an average GI50 of 245nM. And in 46 primary human tumors including small cell lung, mammary cancer and melanoma, the mean IC50 is 750nM. Additionally, treatment of NVP-BEP800 induces apoptosis in human breast cancer cell lines. The antitumor efficacy of NVP-BEP800 is also observed with a dose of 15 or 30 mg/kg/d in A375 xenograft-bearing mice as well as in BT-474 breast cancer xenografts [1].

References:
[1] Massey AJ, Schoepfer J, Brough PA, Brueggen J, Chène P, Drysdale MJ, Pfaar U, Radimerski T, Ruetz S, Schweitzer A, Wood M, Garcia-Echeverria C, Jensen MR. Preclinical antitumor activity of the orally available heat shock protein 90 inhibitor NVP-BEP800. Mol Cancer Ther. 2010 Apr;9(4):906-19.

Chemical Properties

StorageStore at -20°C
M.Wt480.4
Cas No.847559-80-2
FormulaC21H23Cl2N5O2S
Solubility≥24.7 mg/mL in DMSO with ultrasonic and warming, <1.98 mg/mL in H2O, ≥16 mg/mL in EtOH with gentle warming
Chemical Name2-amino-4-[2,4-dichloro-5-(2-pyrrolidin-1-ylethoxy)phenyl]-N-ethylthieno[2,3-d]pyrimidine-6-carboxamide
SDFDownload SDF
Canonical SMILESCCNC(=O)C1=CC2=C(N=C(N=C2S1)N)C3=CC(=C(C=C3Cl)Cl)OCCN4CCCC4
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

激酶实验 [1]:

竞争性结合荧光偏振实验

将重组Hsp90β、TAMRA-radicicol或各种浓度的NVP-BEP800加到实验缓冲液(50 mM TRIS pH 7.4,5 mM MgCl2,150 mM KCl和0.1% CHAPS)中, 将其混合,置于室温下孵育30 ~ 45分钟,然后读数。采用共聚焦技术进行2D-FIDA-based HTS实验。NVP-BEP800替代高亲和力配体TAMRA-radicicol,结合到Hsp90β上。检测上述过程导致的荧光偏振降低。绘制竞争曲线,计算IC50值。

细胞实验 [1]:

细胞系

BT-474细胞

制备方法

在DMSO中的溶解度有限。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C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 °C可放置数月。

反应条件

50 ~ 500 nM;24小时

实验结果

在BT-474细胞中,NVP-BEP800呈浓度依赖性地降低Akt (Ser473) 和ErbB2磷酸化水平。在500 nM的剂量下,Akt在Ser473处的磷酸化程度低于检测限,Akt和ErbB2水平也较低。

动物实验 [1]:

动物模型

携带乳腺癌BT-474细胞异种移植瘤的小鼠

给药剂量

15或30 mg/kg/day;口服给药

实验结果

在携带乳腺癌BT-474细胞异种移植瘤的小鼠中,NVP-BEP800呈剂量依赖性地促进Hsp90-p23复合体解离,并且降低ErbB2、p-Akt和p-S6稳态水平。每天按30 mg/kg剂量处理导致38%的肿瘤衰退。每天按15 mg/kg剂量处理,其T/C值为36%。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Massey AJ, Schoepfer J, Brough PA, Brueggen J, Chène P, Drysdale MJ, Pfaar U, Radimerski T, Ruetz S, Schweitzer A, Wood M, Garcia-Echeverria C, Jensen MR. Preclinical antitumor activity of the orally available heat shock protein 90 inhibitor NVP-BEP800. Mol Cancer Ther. 2010 Apr;9(4):906-19.

生物活性

描述 NVP-BEP800是一种新型的,全合成的HSP90β口服抑制剂,IC 50为58 nM。
靶点 Hsp90β          
IC50 58 nM          

质量控制

化学结构

NVP-BEP800