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    InvivoChem Cat #: V0892
    CAS #: 847559-80-2Purity ≥98%

    Description: NVP-BEP800 (VER-82576; NVP BEP-800; BEP-800) is a novel, potent, fully synthetic, orally bioavailable heat shock protein 90β (HSP90β) inhibitor with potential antitumor activity. It inhibits HSP90β with an IC50 of 58 nM. NVP-BEP800 exhibits excellent antitumor efficacy in the A375 melanoma xenograft model.

    References: Mol Cancer Ther. 2010 Apr;9(4):906-19.

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    Molecular Weight (MW)480.41
    CAS No.847559-80-2
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 15 mg/mL (31.2 mM)
    Water: <1 mg/mL
    Ethanol: <1 mg/mL
    Solubility (In vivo)0.5% methylcellulose: 5 mg/mL
    SynonymsVER 82576; NVP BEP800; NVP-BEP 800; VER82576; VER-82576; NVP BEP-800; BEP-800; BEP800; BEP 800.

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    In Vitro

    In vitro activity: NVP-BEP800 is an ATP-competitive inhibitor of Hsp90β with an IC50 of 58 nM, exhibiting >70-fold selectivity against Hsp90 family members Grp94 and Trap-1 with IC50 values of 4.1 μM and 5.5 μM, respectively. NVP-BEP800 displays no inhibitory activity against the closely related GHKL ATPase, topoisomerase II, and the structurally unrelated ATPase, Hsp70 at the concentration of 10 μM. NVP-BEP800 potently inhibits the proliferation of various tumor cell lines with GI50 values ranging from 38 nM in A375 to 1.05 μM in PC3, and primary human tumors with the mean IC50 of 0.75 μM and IC70 of 1.8 μM. NVP-BEP800 treatment at the concentration of five times the GI50 increases the percentage of G2-M phase in A2058 and A549 cells and sub-G1 phase in BT-474, HCT116, A2058 and A549 cells by 29.5%, 33.6%, 42.7%, 12.1%, 5.9% and 7.1%, respectively. NVP-BEP800 treatment causes Akt and ErbB2 dephosphorylation, ErbB2 degradation, and Hsp70 induction in a concentration-dependent manner in BT-474 cells with IC50 values of 218 nM, 39.5 nM, 137 nM and 207 nM, respectively.

    Kinase Assay: Recombinant Hsp90β, TAMRA-radicicol, or various concentrations of NVP-BEP800 is 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 to 45 minutes prior to reading. The 2D-FIDA-based HTS assay based on confocal technologies monitors the decreased fluorescence polarization on displacement of the high affinity ligand TAMRA-radicicol from Hsp90β by NVP-BEP800. The concentration of NVP-BEP800 which inhibits Hsp90β by 50% is determined from the competition curve.

    Cell Assay: Cells (A375, PC3, A2058, A549, HCT116, BT-474, SKBr3, MCF-7, MDAMB-157, MDA-MB-231, MDA-MB-468, and BT20) are exposed to NVP-BEP800 for 24 hours. Cell proliferation is determined using either sulforhodamine B for adherent cells or MTS assay for suspension cells or those showing low adherence. Cell death is determined using a ToxiLight nondestructive cytotoxicity bioassay kit. Cell cycle progression is determined by RNase A/propidium iodide staining following fixation in 70% ethanol. Caspase-3/7 activity is determined using a homogeneous caspase activity kit.

    In VivoOral administration of NVP-BEP800 at 15 or 30 mg/kg/day for 15 days causes a dose-dependent reduction in B-Raf and Akt phosphorylation levels, and displays significant dose-dependent antitumor efficacy in the A375 melanoma xenograft model with the T/C values of 53% and 6% at the dose of 15 and 30 mg/kg/day, respectively, suggesting almost complete tumor inhibition at 30 mg/kg/day. Administration of NVP-BEP800 induces dose-dependent increase of Hsp90-p23 complex dissociation and reductions in the levels of steady-state ErbB2, phospho-Akt and phospho-S6, in BT-474 breast cancer xenografts, and exhibits significant antitumor activity with 38% tumor regression at dose of 30 mg/kg/day and a T/C of 36% at dose of 15 mg/kg/day.
    Animal modelFemale Harlan HsdNpa: Athymic Nude-nu mice injected s.c. with BT-474 or A375 cells
    Formulation & DosageDissolved in  0.5% methyl cellulose; 50 mg/kg; oral gavage

    Mol Cancer Ther. 2010 Apr;9(4):906-19.

    These protocols are for reference only. InvivoChem does not independently validate these methods.


    NVP-BEP800 depletes client proteins in human cancer cell lines in vitro.


    Bioavailability and tolerability of NVP-BEP800 in nude mice. Mol Cancer Ther.2010 Apr;9(4):906-19. 


    NVP-BEP800 induces cell cycle arrest, apoptosis, and cell death in a panel of human breast cancer cell lines.


    Antitumor efficacy, tolerability, and pharmacodynamic effects of NVP-BEP800 in the A375 melanoma xenograft model. Mol Cancer Ther. 2010 Apr;9(4):906-19.


    Antitumor efficacy, tolerability, and pharmacodynamic effects of NVP-BEP800 in the BT-474 human breast cancer xenograft model. Mol Cancer Ther. 2010 Apr;9(4):906-19. 


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