CDDO-Im (RTA-403)是一种合成三萜类化合物，通过与Kelch样ECH相关蛋白1（Keap1）结合抑制核因子E2相关因子（Nrf2）的降解，从而激活Nrf2信号通路并提高其蛋白水平。
Cas No.:443104-02-7
Sample solution is provided at 25 µL, 10mM.
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CDDO-Im (RTA-403) is a synthetic triterpenoid that activates Nuclear factor erythroid 2–related factor 2 (Nrf2) signaling by binding to Kelch-like ECH-associated protein 1 (Keap1), thereby inhibiting Nrf2 degradation and increasing its protein levels[1]. CDDO-Im is a multifunctional molecule with potent antiproliferative, differentiating, and anti-inflammatory activities[2].
In vitro, CDDO-Im is highly active in suppressing cellular proliferation of human leukemia and breast cancer cell lines, with an IC50 of approximately 10-30nM[3]. CDDO-Im treatment at 50, 100 and 200nM for 72h significantly inhibited the growth of both SUM159 and MDA-MB-231 cells[4]. CDDO-Im treatment at 200nM for 24h markedly induced cell cycle arrest at G2/M-phase and late cell apoptosis in both SUM159 cells and MDA-MB-231 cells[4]. After 7 days of treatment with 100nM CDDO-Im, the CD24−/EpCAM+ cancer stem cell subpopulation in SUM159 sphere cultures decreased by 81.2%[4]. Treatment with 3-300mM CDDO-Im for 3 days inhibited the proliferation of MCF-7 cells in a dose-dependent manner[3].
In vivo, oral gavage of 2μmol of CDDO-Im increased Heme Oxygenase-1 (HO-1) protein levels in the stomach, small intestine, colon, liver, lung, kidney, and heart at 6h in male CD-1 mice[2]. Intraperitoneal injection of 10nmol (5.4μg) CDDO-Im in mice nearly completely blocked interferon-induced Inducible Nitric Oxide Synthase (iNOS) at 10h, while 1nmol (0.54μg) produced a partial effect[3]. In the murine leukemia model (L1210 cells i.p. in BDF-1 mice), twice-daily intraperitoneal injection of CDDO-Im at 50μg per dose (100μg/d) for 8 days reduced leukemia cell numbers by 91%[3]. In the murine melanoma model, twice-daily intraperitoneal injection of CDDO-Im at 50μg per dose (100μg/d) for 5 days reduced tumor burden by 75%[3].
References:
[1] Meng, X., Waddington, J.C., Tailor, A., et al.CDDO-imidazolide targets multiple amino acid residues on the Nrf2 adaptor, Keap1J. Med. Chem.63(17)9965-9976(2020).
[2] Liby, K., Hock, T., Yore, M.M., et al.The synthetic triterpenoids, CDDO and CDDO-imidazolide, are potent inducers of heme oxygenase-1 and Nrf2/ARE signalingCancer Res.65(11)4789-4798(2005).
[3] Place AE, Suh N, Williams CR, et al. The novel synthetic triterpenoid, CDDO-imidazolide, inhibits inflammatory response and tumor growth in vivo. Clin Cancer Res. 2003;9(7):2798-2806.
[4] So JY, Lin JJ, Wahler J, Liby KT, Sporn MB, Suh N. A synthetic triterpenoid CDDO-Im inhibits tumorsphere formation by regulating stem cell signaling pathways in triple-negative breast cancer. PLoS One. 2014;9(9):e107616.
CDDO-Im (RTA-403)是一种合成三萜类化合物，通过与Kelch样ECH相关蛋白1（Keap1）结合抑制核因子E2相关因子（Nrf2）的降解，从而激活Nrf2信号通路并提高其蛋白水平[1]。CDDO-Im是一种多功能分子，具有强大的抗增殖、分化和抗炎活性[2]。
体外实验中， CDDO-Im对人类白血病和乳腺癌细胞系的细胞增殖具有显著抑制作用，其IC₅₀约为10-30nM[3]。CDDO-Im在50、100和200nM作用72h后，对SUM159和MDA-MB-231细胞的生长均有明显抑制作用[4]。CDDO-Im在200nM下处理24h可显著诱导SUM159细胞和MDA-MB-231细胞的G2/M期细胞周期阻滞和晚期细胞凋亡[4]。经100nM CDDO-Im处理7天后，SUM159球培养中CD24−/EpCAM+肿瘤干细胞亚群数量减少了81.2%[4]。用3-300mM的CDDO-Im处理3天，可剂量依赖性抑制MCF-7细胞的增殖[3]。
体内实验中，经口灌胃给予2μmol CDDO-Im后，雄性CD-1小鼠在给药6小时后，其胃、小肠、结肠、肝、肺、肾和心脏组织中的血红素加氧酶-1（HO-1）蛋白水平均升高[2]。在小鼠中，腹腔注射10nmol（5.4μg）CDDO-Im 于10小时后几乎完全阻断了干扰素诱导的诱导型一氧化氮合酶（iNOS），而1nmol（0.54μg）仅产生部分作用[3]。在小鼠白血病模型（BDF-1小鼠腹腔注射L1210细胞）中，连续8天每日两次腹腔注射CDDO-Im（每次50μg，合计100μg/天），使白血病细胞数量减少了91%[3]。在小鼠黑色素瘤模型中，连续5天每日两次腹腔注射CDDO-Im（每次50μg，合计100μg/天），使肿瘤负荷减少了75%[3]。
| Cell experiment [1]: | |
Cell lines | SUM159 and MDA-MB-231 cells |
Preparation Method | SUM159 and MDA-MB-231 cells were seeded into each well of 96-well plates (1000 cell/well) and treated the next day with vehicle control or CDDO-Im (1, 10, 50, 100 and 200nM). Cell proliferation was measured by an MTT assay at 0, 24, 48 and 72h time points. |
Reaction Conditions | 1, 10, 50, 100 or 200nM; 0-72h |
Applications | CDDO-Im treatment at 50, 100 and 200nM for 72h significantly inhibited the growth of both SUM159 and MDA-MB-231 cells. |
| Animal experiment [2]: | |
Animal models | Male CD-1 mice |
Preparation Method | Male CD-1 mice were gavaged with 2μmol CDDO-Im dissolved in DMSO or with vehicle alone. After 6 hours, various organs were harvested and Heme Oxygenase-1 (HO-1) induction was analyzed by Western blotting. |
Dosage form | 2μmol; once; p.o. |
Applications | HO-1 protein levels increased in the stomach, small intestine, colon, liver, lung, kidney, and heart of CD-1 mice gavaged with 2μmol CDDO-Im; highest induction of HO-1 was observed in the stomach, liver, and small intestine. |
References: | |
| Cas No. | 443104-02-7 | SDF | |
| 别名 | RTA-403; TP-235; CDDO-Imidazolide | ||
| Canonical SMILES | CC(C)([C@]1([H])CC[C@@]([C@@]2(CC[C@]3(CCC(C)(C[C@@]3([H])[C@]24[H])C)C(N5C=CN=C5)=O)C)6C)C(C(C#N)=C[C@]1(C)C6=CC4=O)=O | ||
| 分子式 | C34H43N3O3 | 分子量 | 541.72 |
| 溶解度 | DMSO : 50 mg/mL (92.30 mM);Water : < 0.1 mg/mL (insoluble) | 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 | 1.846 mL | 9.2299 mL | 18.4597 mL |
| 5 mM | 369.2 μL | 1.846 mL | 3.6919 mL |
| 10 mM | 184.6 μL | 923 μL | 1.846 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
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 | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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