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    InvivoChem Cat #: V0873
    CAS #: 747412-49-3 Purity ≥98%

    Description: Luminespib (also known as NVP AUY922; NVP AUY-922; AUY922; AUY-922; VER52296; VER-52296), a 4,5-diarylisoxazole derivative, is a 3rd generation HSP90 (heat shock protein 90) inhibitor with potential anticancer activity. In inhibits HSP90α/β with IC50s of 13 nM  /21 nM in cell-free assays. Luminespib showed weaker potency against the HSP90 family members GRP94 and TRAP-1, and exhibits the tightest binding of any small-molecule HSP90 ligand. Structurally, luminespib is a derivative of 4,5-diarylisoxazole and a third-generation heat shock protein 90 (Hsp90) inhibitor with potential antineoplastic activity.

    References: Cancer Sci. 2011;102(7):1388-95; Anticancer Res. 2011;31(4):1197-204; Cancer Res. 2008;68(8):2850-60. 

    Related CAS: 747412-49-3 (free); 1051919-21-1 (Luminespib mesylate); 1051919-26-6 (Luminespib mesylate hydrate)

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    Molecular Weight (MW)465.54
    CAS No.747412-49-3
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 93 mg/mL (199.8 mM)
    Water: <1 mg/mL
    Ethanol: 31 mg/mL (66.6 mM)
    Solubility (In vivo)1% DMSO+30% polyethylene glycol+1% Tween 80: 30 mg/mL
    SynonymsLuminespib; NVP AUY922; AUY922; AUY-922; VER52296; VER-52296; NVP AUY-922; NVP-AUY922; NVP-AUY-922; AUY 922; VER 52296 

    Chemical Name: 5-(2,4-dihydroxy-5-isopropylphenyl)-N-ethyl-4-(4-(morpholinomethyl)phenyl)isoxazole-3-carboxamide


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    In Vitro

    In vitro activity: NVP-AUY922 inhibits proliferation of various human cancer cell lines in vitro, with an average GI50 of 9 NM. The IC50 values of NVP-AUY922 fall in the range of 2 to 40 nM in these gastric cancer cell lines. IC50 value for the BEAS-2B cells is 28.49 nM. Treatment with NVP-AUY922 does not influence the expression of HSP90, but expression of HSP70 gets elevated by NVP-AUY922 treatment. NVP-AUY922 increases the binding of HSP70 to HSP90. NVP-AUY922 causes p23 dissociation from the HSP90 complex and can then recruit HSP70 to the HSP90 complex. After the treatment with NVP-AUY922, expression of receptor tyrosine kinases including VEGFR1, 2, 3 and PDGFRɑ is decreased. A decrease is also noticed in the expression of Akt and phospho-Akt. Meanwhile, treatment with NVP-AUY922 causes decreased expression of HER-2 in NCI-N87 cells. NVP-AUY922 treatment results in binding of HSP90 to client proteins and setting them up as targets for degradation by the proteasome. NVP-AUY922 can influence cell growth by affecting multiple signaling pathways. In addition, treatment with the proteasome inhibitor, MG132, restores expression of thymidylate synthase, which is decreased by NVP-AUY922. NVP-AUY922 increases the expression of cleaved caspase-3 leading to apoptosis in HSC-2 cells.

    Kinase Assay: NVP-AUY922 is dissolved in DMSO at a concentration of 10 mM. NVP-AUY922 is assessed against HSP90α, HSP90β, GRP94, TRAP-1, HSP72, and topoisomerase II. Profiling against a panel of kinases has been carried out and screening against a panel of additional enzymes and receptors is performed at Cerep.

    Cell Assay: Human gastric cancer cells NCI-N87 (5-7 ×103 in 50 μL/well) are seeded in 96-well plates and incubated at 37 °C for 24 hours, followed by NVP-AUY922 treatment for 1-3 days at 37 °C. After treatment, the cells are assayed by MTT method and analyzed by microplate reader.

    In VivoTreatment with NVP-AUY922 causes a robust antitumor response and inhibits p-Akt and VEGF expression in an HSC-2 xenograft model. In BT474, NVP-AUY922 shows complete loss of ERBB2 and substantial depletion of ERα, in addition to reductions in CDK4 and phospho-ERK1/2.
    Animal modelFemale NCr athymic mice bearing WM266.4 human melanoma xenografts
    Formulation & DosageDissolved in  DMSO and diluted in sterile saline/Tween 20; 50 mg/kg; i.p. and i.v. injection

    Cancer Sci. 2011 Jul;102(7):1388-95; Anticancer Res. 2011 Apr;31(4):1197-204; Cancer Res. 2008 Apr 15;68(8):2850-60. 

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

    Luminespib (AUY-922, NVP-AUY922)

    NVP-AUY922 induces cell cycle arrest and apoptosis and depletes client proteins in human cancer cells in vitro. Cancer Res. 2008 Apr 15;68(8):2850-60. 

    Luminespib (AUY-922, NVP-AUY922)

    NVP-AUY922 potently inhibits tumor cell and endothelial cell functions in vitro. Cancer Res. 2008 Apr 15;68(8):2850-60. 

    Luminespib (AUY-922, NVP-AUY922)

    NVP-AUY922 achieves therapeutic concentrations in human tumor xenografts in athymic mice. Cancer Res.2008 Apr 15;68(8):2850-60. 

    Luminespib (AUY-922, NVP-AUY922)

    NVP-AUY922 shows therapeutic activity against established PTEN-null U87MG human glioblastoma xenografts. Cancer Res. 2008 Apr 15;68(8):2850-60. 

    Luminespib (AUY-922, NVP-AUY922)

    NVP-AUY922 shows therapeutic activity against established BRAF mutant WM266.4 human melanoma xenografts and lung metastases. Cancer Res. 2008 Apr 15;68(8):2850-60. 

    Luminespib (AUY-922, NVP-AUY922)

    Luminespib (AUY-922, NVP-AUY922)


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