NVP-BEP800
(Synonyms: NVP-BEP800) 目录号 : GC11179
An Hsp90 inhibitor
Cas No.:847559-80-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Kinase experiment [1]: | |
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Competitive binding fluorescent polarization assay |
Recombinant Hsp90β, TAMRA-radicicol, or various concentrations of NVP-BEP800 was added in assay buffer (50 mM TRIS pH 7.4, 5 mM MgCl2, 150 mM KCl and 0.1% CHAPS), mixed and incubated at room temperature for 30 ~ 45 mins prior to reading. The 2D-FIDA-based HTS assay based on confocal technologies monitored the decreased fluorescence polarization on displacement of the high affinity ligand TAMRA-radicicol from Hsp90β by NVP-BEP800. The concentration of NVP-BEP800 which inhibited Hsp90β by 50% was determined from the competition curve. |
| Cell experiment [1]: | |
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Cell lines |
BT-474 cells |
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Preparation method |
The solubility of this compound in DMSO is limited. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
50 ~ 500 nM; 24 hrs |
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Applications |
In BT-474 cells, NVP-BEP800 concentration-dependently decreased phospho-Akt (Ser473) and ErbB2 levels. At the dose of 500 nM, phosphorylation of Akt at Ser473 was not detectable, and lower levels of Akt and ErbB2 were also detected. |
| Animal experiment [1]: | |
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Animal models |
Mice bearing breast cancer BT-474 cell xenografts |
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Dosage form |
15 or 30 mg/kg/day; p.o. |
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Applications |
In mice bearing breast cancer BT-474 cell xenografts, NVP-BEP800 dose-dependently increased Hsp90-p23 complex dissociation and lowered the levels of steady-state ErbB2, phospho-Akt as well as phospho-S6. NVP-BEP800 induced 38% tumor regression at dose of 30 mg/kg/day and a T/C value of 36% at dose of 15 mg/kg/day. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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. | |
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.
| Cas No. | 847559-80-2 | SDF | |
| 别名 | NVP-BEP800 | ||
| 化学名 | 2-amino-4-[2,4-dichloro-5-(2-pyrrolidin-1-ylethoxy)phenyl]-N-ethylthieno[2,3-d]pyrimidine-6-carboxamide | ||
| Canonical SMILES | CCNC(=O)C1=CC2=C(N=C(N=C2S1)N)C3=CC(=C(C=C3Cl)Cl)OCCN4CCCC4 | ||
| 分子式 | C21H23Cl2N5O2S | 分子量 | 480.4 |
| 溶解度 | ≥ 24.7 mg/mL in DMSO with ultrasonic and warming, ≥ 16 mg/mL in EtOH with gentle warming | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0816 mL | 10.408 mL | 20.816 mL |
| 5 mM | 0.4163 mL | 2.0816 mL | 4.1632 mL |
| 10 mM | 0.2082 mL | 1.0408 mL | 2.0816 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。