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    VER-50589
    VER-50589

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0882
    CAS #: 747413-08-7Purity ≥98%

    Description: VER-50589 (VER 50589; VER50589) is a highly potent and selective HSP90 (Heat Shock Protein 90) inhibitor with potential antineoplastic activity. It inhibits HSP90 with an IC50 of 21 nM for HSP90β. VER-50589 exhibits excellent anti-proliferative activity in vitro with a mean cellular antiproliferative GI50 of 78 nM against a human cancer cell lines. It also demonstrates high in vivo antitumor efficacy in HCT116 human colon cancer xenografts.

    References: Mol Cancer Ther. 2007 Apr;6(4):1198-211.

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    Molecular Weight (MW)388.80
    FormulaC19H17ClN2O5
    CAS No.747413-08-7
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 77 mg/mL (198.0 mM)
    Water: <1 mg/mL
    Ethanol: 77 mg/mL (198.0 mM)
    Other info

    Chemical Name: 5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)isoxazole-3-carboxamide

    InChi Key: JXPCDMPJCKNLBY-UHFFFAOYSA-N

    InChi Code: InChI=1S/C19H17ClN2O5/c1-3-21-19(25)17-16(10-4-6-11(26-2)7-5-10)18(27-22-17)12-8-13(20)15(24)9-14(12)23/h4-9,23-24H,3H2,1-2H3,(H,21,25)

    SMILES Code: O=C(C1=NOC(C2=CC(Cl)=C(O)C=C2O)=C1C3=CC=C(OC)C=C3)NCC

    Synonyms

    VER 50589; VER-50589; VER50589; 


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    In Vitro

    In vitro activity: VER-50589 inhibits the intrinsic ATPase activity of recombinant yeast Hsp90 with IC50 of 143 nM, and produces antiproliferative activity in a panel of human cancer cell lines and nontumorigenic cells in vitro. VER-50589 causes induction of HSP72 and HSP27 alongside depletion of client proteins, including C-RAF, B-RAF, and survivin, and the protein arginine methyltransferase PRMT5, which further result in cell cycle arrest and apoptosis.


    Kinase Assay: Binding of HSP90 inhibitors to human full-length recombinant HSP90β is determined by a competitive binding fluorescence polarization assay, using a fluorescent pyrazole resorcinol probe.


    Cell Assay: Antiproliferative effects are measured using the sulforhodamine B assay. HUVEC sensitivity is determined by an alkaline phosphatase method. Cells: Melanoma cells (SKMEL 2, SKMEL 5, SKMEL 28, WM266.4); Colon cancer cells (HCT116, BEneg, BE2, HT29, HT29oxaliR); Ovarian cancer cells (CH1, CH1doxR); Breast cancer cells (MB-231, MB-468, BT20, ZR751, MCF7, BT-474); nontumorigenic cells (HUVEC, MCF10a, PNT)

    In VivoIn HCT116 human colon cancer xenografts, VER-50589 (100 mg/kg i.p.) results in a statistically significant reduction of ∼30% in tumor volume and weight, as well as induction of HSP72 and depletion of ERBB2 and C-RAF.
    Animal modelHCT116 human colon cancer xenografts
    Formulation & DosageDissolved in 10% DMSO, 5% Tween 20, 85% saline; 100 mg/kg; i.p. injection
    References

    Mol Cancer Ther. 2007 Apr;6(4):1198-211.


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

    VER-50589

    Pymol diagrams showing binding interactions between the ATP-binding site of human HSP90α and (A) VER-49009 and (B) VER-50589. Mol Cancer Ther. 2007 Apr;6(4):1198-211.
     

    VER-50589

    Effects of VER-49009 and VER-50589 on molecular biomarkers and apoptosis.


    VER-50589

    Pharmacokinetics of VER-49009 and VER-50589. Mol Cancer Ther. 2007 Apr;6(4):1198-211.
     

    VER-50589

    Effects of VER-49009 and VER-50589 on HSP72 induction and client protein depletion in vivo. Mol Cancer Ther. 2007 Apr;6(4):1198-211.


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