| Bardoxolone methylIKK inhibitor, potent antioxidant inflammation modulator |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
Nature.2018 Nov;563(7731):407-411.Nature.2018 Jun 13.Nature.2018 Jun 27.Nature.2018 Mar 29;555(7698):673-677.Nature.2017 Sep 7;549(7670):96-100.Nature.2016 Apr 21;532(7599):398-401.
Science.2016 Aug 5;353(6299)594-8Nat Nanotechnol.2017 Dec;12(12):1190-1198.Nature Biotechnology.2017 Jun;35(6):569-576Nat Med.2018 Sep 17.Cell.2018 Dec 21. pii: S0092-8674(18)31561-7.Cell.Available online 25 October 2018.Cell.2018 Sep 27. pii: S0092-8674(18)31183-8.Cell.2018 Jun 28;174(1):172-186.e21.Cell.2018 Feb 22;172(5):1007-1021.e17.Cell.2017 Nov 30;171(6):1284-1300.e21.Cell.2017 Aug 17. pii: S0092-8674(17)30869-3.Cell.2017 Jul 13;170(2):312-323Nat Med.2018 Jan 29.Nat Med.2017 Nov;23(11):1342-1351.Cell.2017 Apr 6;169(2):286-300.Cell.2015 Aug 27;162(5):987-1002.Cell.2015 Feb 12;160(4):729-44.Nature Medicine.2017 Apr;23(4):493-500.Cancer Cell.2018 May 14;33(5):905-921.e5.Cancer Cell.2018 Apr 9;33(4):752-769.e8.Cancer Cell.2018 Mar 12;33(3):401-416.e8.Cancer Cell.2017 Aug 14;32(2):253-267.e5.Nat Methods.2018 Jul;15(7):523-526.Cell Stem Cell.2018 May 3;22(5):769-778.e4.Cell Stem Cell.2017 Nov 20. pii: S1934-5909(17)30375-2.Quality Control & MSDS
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- Purity = 98.12%
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Chemical structure
| Description | Bardoxolone methyl is an oral modulator of antioxidant inflammation. | |||||
| Targets | antioxidant inflammation | |||||
| IC50 | ||||||
| Kinase experiment [1]: | |
IKK assay | To determine the effect of CDDO-Me on TNF-induced IKK activation, IKK was 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 hrs, the beads were 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 mins, the reaction was terminated by boiling with SDS sample buffer for 5 mins. Finally, the protein was resolved on 10% SDS-PAGE, the gel was dried, and the radioactive bands were visualized with a Storm820. To determine the total amounts of IKK-α and IKK-β in each sample, 50 μg of whole-cell proteins were 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 experiment [2]: | |
Cell lines | HL-60, KG-1 and NB4 cells |
Preparation method | The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reaction Conditions | ~ 5 μM; 72 hrs |
Applications | In leukemia cells, such as HL-60, KG-1, and NB4 cells, Bardoxolone Methyl decreased cell viability with the IC50 values of 0.4, 0.4 and 0.27 μM, respectively. |
| Animal experiment [3]: | |
Animal models | Female A/J mice i.p. injected with vinyl carbamate |
Dosage form | 60 or 400 mg/kg; p.o.; the mice fed Bardoxolone Methyl for 2 weeks and then switched to a week of control diet, for 15 weeks. |
Applications | At the dose of 60 mg, Bardoxolone Methyl reduced the number, size, as well as severity of lung tumors in vivo. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: [1]. Shishodia S, Sethi G, Konopleva M, Andreeff M, Aggarwal BB. A synthetic triterpenoid, CDDO-Me, inhibits IkappaBalpha kinase and enhances apoptosis induced by TNF and chemotherapeutic agents through down-regulation of expression of nuclear factor kappaB-regulated gene products in human leukemic cells. Clin Cancer Res. 2006 Mar 15;12(6):1828-38. [2]. Konopleva M, Tsao T, Ruvolo P, Stiouf I, Estrov Z, Leysath CE, Zhao S, Harris D, Chang S, Jackson CE, Munsell M, Suh N, Gribble G, Honda T, May WS, Sporn MB, Andreeff M. Novel triterpenoid CDDO-Me is a potent inducer of apoptosis and differentiation in acute myelogenous leukemia. Blood. 2002 Jan 1;99(1):326-35. [3]. Liby K, Royce DB, Williams CR, Risingsong R, Yore MM, Honda T, Gribble GW, Dmitrovsky E, Sporn TA, Sporn MB. The synthetic triterpenoids CDDO-methyl ester and CDDO-ethyl amide prevent lung cancer induced by vinyl carbamate in A/J mice. Cancer Res. 2007 Mar 15;67(6):2414-9. | |
Bardoxolone methyl Dilution Calculator
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| Cas No. | 218600-53-4 | SDF | Download SDF |
| Synonyms | NSC 713200; RTA 402; CDDO Methyl ester | ||
| 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 | ||
| Canonical SMILES | CC1(CCC2(CCC3(C(C2C1)C(=O)C=C4C3(CCC5C4(C=C(C(=O)C5(C)C)C#N)C)C)C)C(=O)OC)C | ||
| Formula | C32H43NO4 | M.Wt | 505.69 |
| Solubility | ≥25.3 mg/mL in DMSO, <2.15 mg/ml="" in="" etoh,=""><2.52 mg/ml="" in="" h2o=""> | Storage | Store at -20°C |
| Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
Bardoxolone methyl is an activator of the KEAP1-Nrf2 pathway [1] and also inhibits the pro-inflammatory transcription factor NF-kB [2] which can protect kidneys from aristolochic acid (AA)-induced acute kidney injury (AKI) with IC50 value of 1.5 nM and LC50 value of 2.1 µM [3].Nrf2, a transcription factor, is a basic leucine zipper (bZIP) protein that regulates the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation [4], such as NADPH, Glutathione, SRXN1, TXNRD1, HMOX1, GST, UGT and Mrps. Nrf2 plays an important role in the maintenance of homeostasis which can control the basal and inducible expression of a battery of genes with diverse physiological roles, including the preservation of redox balance, the metabolism and detoxification of xenobiotics, and the regulation of multiple metabolic pathways that ensure the provision of cellular energy[5]. Bardoxolone methyl is a synthetic oleanane triterpenoid compound, which has no effect on the function and histology of normal kidneys but increased renal expression of Nrf2, HO-1 and NQO1 by western blotting analysis of mice kidneys and immunofluorescence staining, and can prevent AA-induced acute kidney injury and reduce AAI-induced TI injury in mRNA and protein levels through real-time PCR.[6] In conclusion, Bardoxolone methyl can prevent AAI-induced renal damage, and it may exert this renoprotective effects by activating the Nrf2 signaling pathway and inducing the downstream target genes expression. A phase 3 clinical trial evaluating bardoxolone methyl for the treatment of chronic kidney disease (CKD) was terminated in October 2012 after patients treated with the drug were found to have experienced a higher rate of heart-related adverse events, including heart failure, hospitalizations and deaths.[7] Now in 2014, Kyowa Hakko Kirin announced plans to evaluate both safety and efficacy of bardoxolone methyl in a Phase 2 clinical study to be performed in Japan for the treatment of CKD associated with type 2 diabetes.[8]References:1.Yates MS, Tauchi M, Katsuoka F, et al."Pharmacodynamic characterization of chemopreventive triterpenoids as exceptionally potent inducers of Nrf2-regulated genes." Mol Cancer Ther 2007, 6 (1): 154–62.2.Ahamd R, Raina D, Meyer C, et al.. "Triterpenoid CDDO-Me blocks the NF-kappaB pathway by direct inhibition of IKKbeta on Cys-179.". J Biol Chem, 2006, 281 (47): 35764–9.3.Ian M. Copple. et al. Chemical Tuning Enhances Both Potency Toward Nrf2 and In Vitro Therapeutic Index of Triterpenoids. TOXICOLOGICAL SCIENCES,2014,140(2), 462–469.4.Gold R, Kappos L. Et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N. Engl. J. Med. 2012, 367 (12): 1098–107.5.Ma, Q. Role of nrf2 in oxidative stress and toxicity. Annu. Rev. Pharmacol. Toxicol. 2013,53:401–426.6.Juan Wua. et al. Bardoxolone methyl (BARD) ameliorates aristolochic acid (AA)-induced acute kidney injury through Nrf2 pathway. Toxicology. 2014, 318(6):22–31.7.de Zeeuw D, Akizawa T, Audhya P, et al. "Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease.". N Engl J Med,2013,369 (26): 2492–503. 8.Kyowa Hakko Kirin Co Ltd announces future development direction for bardoxolone methyl (RTA 402).
