In vitro: Bardoxolone 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.
In vivo: Bardoxolone (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.
|Cell lines||HL-60, KG-1, and NB4 cells|
|Preparation method||Leukemic cell lines are cultured at a density of 3.0 × 10^5 cells/mL, and AML mononuclear cells are cultured at 5 × 10^5 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.|
|Incubation time||72 hours|
|Animal models||Female A/J mice are injected i.p. with vinyl carbamate.|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||21 mg/mL in DMSO|
Risk factors for heart failure in patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl.
Chin MP, et al. J Card Fail. 2014 Dec;20(12):953-8. PMID: 25307295.
Mechanisms contributing to adverse cardiovascular events in patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl.
Chin MP, et al. Am J Nephrol. 2014;39(6):499-508. PMID: 24903467.
Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease.
de Zeeuw D, et al. N Engl J Med. 2013 Dec 26;369(26):2492-503. PMID: 24206459.
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