product name Bardoxolone Methyl
Description: Bardoxolone Methyl (also known as “TA 402 and CDDO-methyl ester) is an orally-available IKK inhibitor, showing potent proapoptotic and anti-inflammatory activities. Bardoxolone methyl is a first-in-class synthetic triterpenoid belonging to the antioxidant inflammation modulator (AIM) class. It is the most potent known inducer of the Nrf2 pathway to enter clinical development and works to suppress both oxidative stress and inflammation.
References: J Med Chem. 2000 Nov 2;43(22):4233-46.
505.69
Formula
C32H43NO4
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
Synonyms
RTA 402, TP-155, NSC 713200, CDDO Methyl Ester
other peoduct :
| 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 Vivo | Bardoxolone 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 model | Female A/J mice are injected i.p. with vinyl carbamate. |
| Formulation & Dosage | Dissolved 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. |
