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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Bardoxolone Methyl (also called NSC 713200; NSC-713200; RTA 402; RTA-402 and CDDO-methyl ester) is a novel, potent, orally bioavailable IKK inhibitor with potent proapoptotic and anti-inflammatory properties.
| Targets |
Nrf2; IKK; Ferroptosis;NF-κB
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| ln Vitro |
Bardoxolone Methyl exhibits strong inhibitory effects on interferon-Ƴ induced nitric oxide synthesis in mouse macrophages, with an IC50 value of 0.1 nM. [1] With IC50 values of 0.4, 0.4, and 0.27 μM, respectively, bardoxolone methyl reduces the viability of leukemic HL-60, KG-1, and NB4 cells. Apoptosis is induced by CDDO-Me in part because it induces pro-apoptotic Bax protein, prevents ERK1/2 from being activated, and prevents Bcl-2 from being phosphorylated. [2] When TNF, interleukin (IL)-1beta, phorbol ester, okadaic acid, hydrogen peroxide, lipopolysaccharide, and cigarette smoke activate NF-kappaB, bardoxolone methyl potently inhibits both constitutive and inducible NF-kappaB. [3]
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| ln Vivo |
Bardoxolone Methyl (60 mg/kg) reduces the number, size, and severity of lung tumors in vivo. [4] Bardoxolone Methyl induces HO-1 protein expression in the spleen, protects mice from lethal-dose LPS, and significantly reduces the in vivo inflammatory cytokine response following LPS challenge. [5]
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| Enzyme Assay |
IKK is analyzed to ascertain how CDDO-Me affects TNF-induced IKK activation. In a nutshell, antibody against IKKα and IKKβ was used to precipitate the IKK complex from whole-cell extracts, and protein A/G-Sepharose beads were used as the final step. 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). The reaction is stopped by boiling for five minutes with SDS sample buffer following a 30-minute incubation period at 30°C. When the gel has dried and the radioactive bands can be seen with a Storm820, the protein has been resolved on a 10% SDS-PAGE. 50 g of whole-cell proteins are resolved on 7.5% SDS-PAGE, electrotransferred to a nitrocellulose membrane, and then blotted with either an anti-IKK-α or anti-IKK-β antibody to determine the total concentrations of IKK-α and IKK-β in each sample.
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| 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 the indicated concentrations of CDDO-Me. A suitable amount of DMSO (final concentration less than 0.05%) is used as a control. 1 M ara-C is added to the cultures for cytotoxicity tests. A hematocytometer is used to count viable cells using the trypan blue dye exclusion method after 24 to 72 hours.
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| Animal Protocol |
The cynomolgus monkeys are used in two distinct in-life studies. In one study, amorphous bardoxolone methyl is given orally to cynomolgus monkeys (n=9/gender/dose group) using sesame oil as the vehicle at 5, 30, and 300 mg/kg once daily for 12 months in a GLP environment. All animals are observed twice daily for morbidity, mortality, injuries, and the availability of food and water. Weekly clinical assessments and body weight measurements are made and recorded. Analysis of weight data involves computing the linear trapezoidal method's area under the weight versus time curve. All animals are pre-tested, and blood samples are taken before interim (6-month) and terminal (12-month) necropsies from all animals in order to perform clinical chemistry evaluations. For every dose group, a second group of monkeys is given four weeks to recover.
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| References |
| Molecular Formula |
C32H43NO4
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| Molecular Weight |
505.69
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| Exact Mass |
505.32
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| Elemental Analysis |
C, 76.00; H, 8.57; N, 2.77; O, 12.66
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| CAS # |
218600-53-4
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| Related CAS # |
Bardoxolone;218600-44-3
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| Appearance |
White to off-white solid powder
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| SMILES |
C[C@@]12CC[C@]3(CCC(C[C@H]3[C@H]1C(=O)C=C4[C@]2(CC[C@@H]5[C@@]4(C=C(C(=O)C5(C)C)C#N)C)C)(C)C)C(=O)OC
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| InChi Key |
WPTTVJLTNAWYAO-KPOXMGGZSA-N
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| InChi Code |
InChI=1S/C32H43NO4/c1-27(2)11-13-32(26(36)37-8)14-12-31(7)24(20(32)17-27)21(34)15-23-29(5)16-19(18-33)25(35)28(3,4)22(29)9-10-30(23,31)6/h15-16,20,22,24H,9-14,17H2,1-8H3/t20-,22-,24-,29-,30+,31+,32-/m0/s1
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| Chemical Name |
methyl (4aS,6aR,6bS,8aR,12aS,14aR,14bS)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,3,4,5,6,7,8,8a,14a,14b-decahydropicene-4a-carboxylate
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.94 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.94 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 2.5 mg/mL (4.94 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 4: 4% DMSO+30% PEG 300+5% Tween+ddH2O: 5mg/mL Solubility in Formulation 5: 5 mg/mL (9.89 mM) in Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 6: 10 mg/mL (19.77 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; Need ultrasonic and warming and heat to 40°C. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9775 mL | 9.8875 mL | 19.7750 mL | |
| 5 mM | 0.3955 mL | 1.9775 mL | 3.9550 mL | |
| 10 mM | 0.1977 mL | 0.9887 mL | 1.9775 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01503866 | Completed | Drug: bardoxolone methyl | Healthy | Reata Pharmaceuticals, Inc. | December 2011 | Phase 1 |
| NCT00664027 | Completed | Drug: RTA 402 (Bardoxolone Methyl) |
Diabetic Nephropathy | UReata Pharmaceuticals, Inc. | April 2008 | Phase 2 |
| NCT01563562 | Completed | Drug: bardoxolone methyl | Healthy Volunteers | Reata Pharmaceuticals, Inc. | October 2011 | Phase 1 |
| NCT04494646 | Completed | Drug: Bardoxolone Methyl Drug: Placebo |
Covid19 | NYU Langone Health | September 8, 2020 | Phase 2 |
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