NVP-BEP800 (Synonyms: NVP-BEP800) |
Catalog No.GC11179 |
An Hsp90 inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 847559-80-2
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment [1]: | |
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]: | |
Cell lines |
BT-474 cells |
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. |
Reacting condition |
50 ~ 500 nM; 24 hrs |
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]: | |
Animal models |
Mice bearing breast cancer BT-474 cell xenografts |
Dosage form |
15 or 30 mg/kg/day; p.o. |
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. |
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. |
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 | |
Synonyms | NVP-BEP800 | ||
Chemical Name | 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 | ||
Formula | C21H23Cl2N5O2S | M.Wt | 480.4 |
Solubility | ≥ 24.7 mg/mL in DMSO with ultrasonic and warming, ≥ 16 mg/mL in EtOH with gentle warming | Storage | Store at -20°C |
General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
Prepare stock solution | |||
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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
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