Bardoxolone methyl
(Synonyms: 甲基巴多索隆; RTA 402; NSC 713200; CDDO Methyl ester) 目录号 : GC11572
Bardoxolone methyl是核因子红细胞2相关因子2（Nrf2）介导的抗氧化和抗炎反应的有效激活剂，也是NF-κB通路的抑制剂。
Cas No.:218600-53-4
Sample solution is provided at 25 µL, 10mM.
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Bardoxolone methyl is an effective activator of the antioxidant and anti-inflammatory response mediated by nuclear factor erythroid 2-related factor 2 (Nrf2), and it is also an inhibitor of the NF-κB pathway [1]. Nrf2 is a transcription factor, a basic leucine zipper (bZIP) protein, which regulates the expression of antioxidant proteins. These antioxidant proteins can prevent oxidative damage caused by damage and inflammation [2]. Bardoxolone methyl can inhibit ferroptosis and induce apoptosis and autophagy in cancer cells. Bardoxolone methyl has been used to treat chronic kidney disease, cancer (including leukemia and solid tumors), and other diseases [3-4].
In vitro, Bardoxolone methyl (0.3, 1.0μM; 4h) significantly reduced mitochondrial damage induced by paclitaxel in 50B11 cells, reversed the reduction in mitochondrial membrane potential (MMP) and the increase in mitochondrial volume induced by paclitaxel, and significantly increased the intensity of pNrf2 in the cells [5]. Bardoxolone methyl (5μM; 72h) significantly reduced the cell viability of leukemia cells (HL-60, KG-1, and NB4 cells) with IC50 values of 0.4, 0.4, and 0.27μM, respectively [6].
In vivo, Bardoxolone methyl (5, 10mg/kg; single dose; oral gavage) alleviated oxidative stress, histopathological damage, and cell apoptosis in the kidneys of rats with acetaminophen-induced acute kidney injury in a dose-dependent manner, and also reduced the expression of KIM-1, NGAL, and TNF-α in the kidneys [7]. Bardoxolone methyl (1, 3, 10mg/kg; twice a day, 4d; i.p.) significantly improved neuropathic pain induced by paclitaxel in rats, increased the expression of pNRf2 and HO-1 in the lumbar dorsal root ganglion (DRG), and reduced the levels of pNFκB and MCP-1 [5].
References:
[1] Reisman SA, Chertow GM, Hebbar S, Vaziri ND, Ward KW, Meyer CJ. Bardoxolone methyl decreases megalin and activates nrf2 in the kidney. J Am Soc Nephrol. 2012;23(10):1663-1673.
[2] Bellezza I, Giambanco I, Minelli A, Donato R. Nrf2-Keap1 signaling in oxidative and reductive stress. Biochim Biophys Acta Mol Cell Res. 2018;1865(5):721-733.
[3] Schiavoni V, Di Crescenzo T, Membrino V, et al. Bardoxolone Methyl: A Comprehensive Review of Its Role as a Nrf2 Activator in Anticancer Therapeutic Applications[J]. Pharmaceuticals, 2025, 18(7): 966.
[4] Wang Y Y, Yang Y X, Zhe H, et al. Bardoxolone methyl (CDDO-Me) as a therapeutic agent: an update on its pharmacokinetic and pharmacodynamic properties[J]. Drug design, development and therapy, 2014: 2075-2088.
[5] Kim HK, Wang Q, Hwang SH, Dougherty PM, Wang J, Abdi S. Bardoxolone Methyl Ameliorates Chemotherapy-Induced Neuropathic Pain by Activation of Phosphorylated Nuclear Factor Erythroid 2-Related Factor 2 in the Dorsal Root Ganglia. Anesth Analg. 2024;138(3):664-675.
[6] 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.
[7] Teksen Y, Kadıoglu E, Ozatik F Y, et al. Bardoxolone methyl attenuates acetaminophen-induced acute kidney injury by suppressing oxidative stress, inflammation and apoptosis[J]. 2024.
Bardoxolone methyl是核因子红细胞2相关因子2（Nrf2）介导的抗氧化和抗炎反应的有效激活剂，也是NF-κB通路的抑制剂 [1]。Nrf2是一种转录因子，是一种碱性亮氨酸拉链（bZIP）蛋白，它调节抗氧化蛋白的表达，这些抗氧化蛋白可以防止损伤和炎症引起的氧化损伤 [2]。Bardoxolone Methyl可抑制铁死亡并在癌细胞中诱导凋亡和自噬。Bardoxolone methyl已用于治疗慢性肾脏病、癌症（包括白血病和实体瘤）和其他疾病 [3-4]。
在体外，Bardoxolone methyl（0.3,1.0μM; 4h）显著减少了紫杉醇诱导的50B11细胞线粒体损伤，逆转了紫杉醇诱导的线粒体膜电位（MMP）降低和线粒体体积增加，并显著增加了细胞中pNrf2的强度 [5]。Bardoxolone methyl（5μM; 72h）显著降低了白血病细胞（HL-60、KG-1和NB4细胞）的细胞活力，其IC50值分别为0.4、0.4和0.27μM [6]。
在体内，Bardoxolone methyl (5, 10mg/kg; single dose; oral gavage)以剂量依赖性的方式缓解了乙酰氨基酚诱导的急性肾损伤大鼠肾脏的氧化应激、组织病理损伤和细胞凋亡，还降低了肾脏中的KIM-1、NGAL和TNF-α的表达 [7]。Bardoxolone methyl（1, 3, 10mg/kg; twice a day, 4d; i.p.）显著改善了紫杉醇诱导的大鼠的神经性疼痛，增加了腰段背根神经节（DRG）中pNRf2和HO-1的表达，降低了pNFκB和MCP-1水平 [5]。
| Cell experiment [1]: | |
Cell lines | 50B11 DRG cells |
Preparation Method | To measure the mitochondrial membrane potential (MMP) and mitochondrial volume, the cells were cultured in NBM with 5% FBS at 1 × 104 cells per well in a 96-well plate for 1 day, treated with Bardoxolone methyl (0.3, 1.0μM) or vehicle (0.1% dimethyl sulfoxide [DMSO] in NBM with 5% FBS) for 4 hours, and then changed to media with paclitaxel (1, 10, 20μM) in NBM with 5% FBS or vehicle (0.2% DMSO in NBM with 5% FBS) for 24 hours. To measure MMP, cells were treated with 5μM JC-1 for 1 hour, after which we measured the fluorescence at excitation at 475nm and emission at 590nm and 530nm, which we calculated as a ratio of 590nm to 530nm. To measure mitochondrial volume, cells were treated with 200nM MitoTracker Green FM probe for 30 minutes and measured the fluorescence at excitation at 490nm and emission at 516nm. |
Reaction Conditions | 0.3,1.0μM; 4h |
Applications | Bardoxolone methyl significantly reduced the mitochondrial damage induced by paclitaxel in 50B11 cells, reversed the decrease in mitochondrial membrane potential (MMP) and the increase in mitochondrial volume induced by paclitaxel. |
| Animal experiment [1]: | |
Animal models | Sprague-Dawley rats |
Preparation Method | Bardoxolone methyl was dissolved in vehicle (5% DMSO and 10% Tween 80 in phosphate-buffered saline without calcium and magnesium) and intraperitoneally injected into rats after PINP had fully developed. To determine the single and extended analgesic effects of BM, we administered as a single intraperitoneal injection (1, 3, 10mg/kg) on day 21 and repeated injections (10mg/kg) twice daily starting on day 21 for 4 days. One hour after the last injection of Bardoxolone methyl on day 22, the lumbar dorsal root ganglia (DRG) were collected. RNA transcriptome, mechanical hyperalgesia, levels of inflammatory mediators and pNrf2, and location of pNrf2 in the DRG were measured by RNA sequencing, von Frey filaments, Western blotting, and immunohistochemistry in rats samples. |
Dosage form | 1, 3, 10mg/kg; twice a day,4d; i.p. |
Applications | Bardoxolone methyl significantly improved neuropathic pain in rats induced by paclitaxel, increased pNRf2 and HO-1 in the lumbar dorsal root ganglion (DRG), and decreased pNFκB and MCP-1 levels. |
References: | |
| Cas No. | 218600-53-4 | SDF | |
| 别名 | 甲基巴多索隆; RTA 402; NSC 713200; CDDO Methyl ester | ||
| 化学名 | 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 | ||
| 分子式 | C32H43NO4 | 分子量 | 505.69 |
| 溶解度 | ≥ 25.3 mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9775 mL | 9.8875 mL | 19.775 mL |
| 5 mM | 0.3955 mL | 1.9775 mL | 3.955 mL |
| 10 mM | 0.1977 mL | 0.9887 mL | 1.9775 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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Quality Control & SDS
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- Purity: >98.50%
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