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    Bardoxolone Methyl
    Bardoxolone Methyl

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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 #: V0754
    CAS #: 218600-53-4Purity ≥98%

    Description: Bardoxolone Methyl (also called NSC 713200; NSC-713200; RTA 402; RTA-402 and CDDO-methyl ester) is a novel, potent, orally bioavailable IKK inhibitor, showing potent proapoptotic and anti-inflammatory activities. 

    References: J Med Chem. 2000 Nov 2;43(22):4233-46.

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    Molecular Weight (MW)505.69
    FormulaC32H43NO4
    CAS No.218600-53-4
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 21 mg/mL (41.5 mM)
    Water: <1 mg/mL
    Ethanol: <1 mg/mL
    Solubility (In vivo)4% DMSO+30% PEG 300+5% Tween+ddH2O: 5mg/mL
    SynonymsNSC-713200; NSC713200; CDDO Methyl Ester; Bardoxolone methyl; CDDOMe; NSC 713200; RTA 402; RTA-402; RTA402;TP-155; TP155; TP 155 



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    In Vitro

    In vitro activity: Bardoxolone Methyl exhibits potent inhibitory activities against production of nitric oxide induced by interferon-Ƴ in mouse macrophages with IC50 of 0.1 NM. Bardoxolone Methyl decreases the viability of leukemic HL-60, KG-1, and NB4 cells with IC50 of 0.4, 0.4, and 0.27 μM, respectively. CDDO-Me induces pro-apoptotic Bax protein, inhibits the activation of ERK1/2, and it blocks Bcl-2 phosphorylation, which contributes to the induction of apoptosis. Bardoxolone Methyl potently inhibits both constitutive and inducible NF-kappaB activated by TNF, interleukin (IL)-1beta, phorbol ester, okadaic acid, hydrogen peroxide, lipopolysaccharide, and cigarette smoke.


    Kinase Assay: To determine the effect of CDDO-Me on TNF-induced IKK activation, IKK is analyzed. Briefly, the IKK complex from whole-cell extracts was precipitated with antibody against IKKα and IKKβ and then treated with protein A/G-Sepharose beads. After 2 hours, the beads are washed with lysis buffer and then resuspended in a kinase assay mixture containing 50 mmol/L HEPES (pH 7.4), 20 mmol/L MgCl2, 2 mmol/L DTT, 20 μCi [γ-32P]ATP, 10 μmol/L unlabeled ATP, and 2 μg of substrate glutathione S-transferase-IκBα (amino acids 1-54). After incubation at 30°C for 30 minutes, the reaction is terminated by boiling with SDS sample buffer for 5 minutes. Finally, the protein is resolved on 10% SDS-PAGE, the gel is dried, and the radioactive bands are visualized with a Storm820. To determine the total amounts of IKK-α and IKK-β in each sample, 50 μg of whole-cell proteins are resolved on 7.5% SDS-PAGE, electrotransferred to a nitrocellulose membrane, and then blotted with either anti-IKK-α or anti-IKK-β antibody.


    Cell Assay: Leukemic cell lines are cultured at a density of 3.0 × 105 cells/mL, and AML mononuclear cells are cultured at 5 × 105 cells/mL in the presence or absence of indicated concentrations of CDDO-Me. Appropriate amounts of DMSO (final concentration less than 0.05%) are included as control. For cytotoxicity studies, 1 μM ara-C is added to the cultures. After 24 to 72 hours, viable cells are counted with the trypan blue dye exclusion method using a hematocytometer.

    In VivoBardoxolone Methyl (60 mg/kg) reduces the number, size, and severity of lung tumors in vivo. Bardoxolone Methyl significantly reduces the in vivo inflammatory cytokine response following LPS challenge, induces HO-1 protein expression in the spleen, and protects mice against lethal-dose LPS.
    Animal modelFemale A/J mice are injected i.p. with vinyl carbamate.
    Formulation & DosageDissolved in DMSO; 60 mg/kg; p.o.
    References

    J Med Chem. 2000 Nov 2;43(22):4233-46; Cancer Res. 2007 Mar 15;67(6):2414-9; J Interferon Cytokine Res. 2010 Jul;30(7):497-508. 


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

    Bardoxolone Methyl

    Synthetic triterpenoid, CDDO-Me pretreatment preserves levels of innate and adaptive immune cell populations in spleen, while lipopolysaccharide (LPS) pretreatment reduces splenocyte immune cell populations. J Interferon Cytokine Res. 2010 Jul; 30(7): 497–508.
     

    Bardoxolone Methyl

    Synthetic triterpenoid, CDDO-Me potently reduces levels of circulating IL-12p70 and IFN-γ (A) and levels of IL-6, IL-17, and IL-23 (B) in response to in vivo lipopolysaccharide (LPS) challenge. Cytokine levels were measured from plasma collected. J Interferon Cytokine Res. 2010 Jul; 30(7): 497–508.
     

    Bardoxolone Methyl

    Lipopolysaccharide (LPS) pretreatment produces changes in whole body (A) and whole spleen (B) weights. J Interferon Cytokine Res. 2010 Jul; 30(7): 497–508.

    Bardoxolone Methyl

    Levels of TLR-inducible IL-6 (A) and IL-10 (B) differ between lipopolysaccharide (LPS)-pretreated mice and mice pretreated with synthetic triterpenoid, CDDO-Me. J Interferon Cytokine Res. 2010 Jul; 30(7): 497–508.
     

    Bardoxolone Methyl

    Heme oxygenase 1 (HO-1) protein expression is increased in both lipopolysaccharide (LPS) (A)- and synthetic triterpenoid, CDDO-Me-pretreated (B) mice. J Interferon Cytokine Res. 2010 Jul; 30(7): 497–508.
     

    Bardoxolone Methyl

    (A) Synthetic triterpenoid, CDDO-Me protects mice against lethal-dose lipopolysaccharide (LPS) challenge. (B) Survival advantage following 200 nmol pretreatment associates with reduction in circulating IL-17 and IFN-γ following LPS challenge. J Interferon Cytokine Res. 2010 Jul; 30(7): 497–508.


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