CDDO-EA
(Synonyms: CDDO ethyl amide; TP319; RTA 405) 目录号 : GC35630
CDDO-EA 是一种 NF-E2 相关因子 2 /抗氧化反应元件 (Nrf2/ARE) 激活剂。
Cas No.:932730-51-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Wild-type and Nrf2−/− mouse embryonic fibroblasts are pre-treated with CDDO-EA or CDDO-TFEA at various concentrations (1, 10 and 100 nM in DMSO) for 18 hours and incubated with 2’,7’-Dichlorodihydrofluorecein diacetate (H2DCFDA) for 30 min. Cells are challenged with 250 µM tBHP for 15-30 min and the mean fluorescence intensity for ~10,000 cells is analyzed by FACSan flow cytometry using a 480-nm excitation wavelength and a 525-nm emission wavelength[1]. |
Animal experiment: | Mice[1] G93A SOD1 transgenic familial ALS mice (high copy number) B6SJL background strain (G93A SOD1, B6SJL-TgGur1) are used. G93A transgenic mice are assigned randomly to the control (vehicle, mouse chaw only) and to mouse chaw containing either CDDO-EA or CDDO-TFEA (400 mg/kg of food, n=30 in both groups). This dose corresponds to about 80 mg/kg body weight/day, assuming each mouse consumes 5 grams of food per day. We found mice can tolerate this dose. Treatments started at two different time regimens: 1) “Early” at 30 days of age, about two months prior to symptom onset; 2) “At Onset” from the onset of the phenotype (80-90 days of age). A diet consisting of either 400 mg of CDDO-TFEA per kg of food or 400 mg of CDDO-EA per kg of food, and a control lab diet, are prepared by Purina. |
References: [1]. Neymotin A, et al. Neuroprotective effect of Nrf2/ARE activators, CDDO ethylamide and CDDO trifluoroethylamide, in a mouse model of amyotrophic lateral sclerosis. Free Radic Biol Med. 2011 Jul 1;51(1):88-96. | |
CDDO-EA is an NF-E2 related factor 2/antioxidant response element (Nrf2/ARE) activator. Nrf2/ARE[1]
CDDO-EA potently activates Nrf2/ARE in a cell culture model of ALS and in the G93A SOD1 mouse model of ALS[1]. CDDO-EA is a potent inducer of apoptosis in A549 lung cancer cells, as shown both by PARP cleavage and Annexin staining. CDDO-EA is more potent than CDDO itself as inducers of heme oxygenase-1 (HO-1). In RAW264.7 macrophage-like cells, CDDO-EA is 7-fold more potent than CDDO as suppressors of the ability of IFN-γ to induce iNOS[2].
The survival analysis shows that G93A mice treated with CDDO-EA, compared to G93A littermate controls, lives significantly longer. CDDO-EA treatment increases the life-span by 20.6 days from 124.05±3.7 days to 144.72±8.1 days (16.6%) (p<0.001). In CDDO-EA-treated G93A mice, the age of death is 141.4±5.2 days and the duration from the age of onset to the age of death is 57.6±7.6 days, which means that the age of death from onset is prolonged by 17.5 days (43%)[1].
[1]. Neymotin A, et al. Neuroprotective effect of Nrf2/ARE activators, CDDO ethylamide and CDDO trifluoroethylamide, in a mouse model of amyotrophic lateral sclerosis. Free Radic Biol Med. 2011 Jul 1;51(1):88-96. [2]. Liby K, et al. 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.
| Cas No. | 932730-51-3 | SDF | |
| 别名 | CDDO ethyl amide; TP319; RTA 405 | ||
| Canonical SMILES | O=C1C(C#N)=C[C@@]2(C)[C@](CC[C@]([C@@]3(C)[C@@]4([H])[C@@]5([H])[C@@](CCC(C)(C)C5)(C(NCC)=O)CC3)(C)C2=CC4=O)([H])C1(C)C | ||
| 分子式 | C33H46N2O3 | 分子量 | 518.73 |
| 溶解度 | DMSO: ≥ 34 mg/mL (65.54 mM) | 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 | 1.9278 mL | 9.6389 mL | 19.2779 mL |
| 5 mM | 0.3856 mL | 1.9278 mL | 3.8556 mL |
| 10 mM | 0.1928 mL | 0.9639 mL | 1.9278 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
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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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Triterpenoid CDDO-EA inhibits lipopolysaccharide-induced inflammatory responses in skeletal muscle cells through suppression of NF-κB
Exp Biol Med (Maywood) 2023 Jan;248(2):175-185.PMID:PMC10041051DOI:10.1177/15353702221139188.
Chronic inflammation is a major contributor to the development of obesity-induced insulin resistance, which then can lead to the development of type 2 diabetes (T2D). Skeletal muscle plays a pivotal role in insulin-stimulated whole-body glucose disposal. Therefore, dysregulation of glucose metabolism by inflammation in skeletal muscle can adversely affect skeletal muscle insulin sensitivity and contribute to the pathogenesis of T2D. The mechanism underlying insulin resistance is not well known; however, macrophages are important initiators in the development of the chronic inflammatory state leading to insulin resistance. Skeletal muscle consists of resident macrophages which can be activated by lipopolysaccharide (LPS). These activated macrophages affect myocytes via a paracrine action of pro-inflammatory mediators resulting in secretion of myokines that contribute to inflammation and ultimately skeletal muscle insulin resistance. Therefore, knowing that synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acids (CDDOs) can attenuate macrophage pro-inflammatory responses in chronic disorders, such as cancer and obesity, and that macrophage pro-inflammatory responses can modulate skeletal muscle inflammation, we first examined whether CDDO-ethyl amide (CDDO-EA) inhibited chemokine and cytokine production in macrophages since this had not been reported for CDDO-EA. CDDO-EA blocked LPS-induced tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), interleukine-1beta (IL-1β), and interleukine-6 (IL-6) production in RAW 264.7 mouse and THP-1 human macrophages. Although many studies show that CDDOs have anti-inflammatory properties in several tissues and cells, little is known about the anti-inflammatory effects of CDDOs on skeletal muscle. We hypothesized that CDDO-EA protects skeletal muscle from LPS-induced inflammation by blocking nuclear factor kappa B (NF-κB) signaling. Our studies demonstrate that CDDO-EA prevented LPS-induced TNF-α and MCP-1 gene expression by inhibiting the NF-κB signaling pathway in L6-GLUT4myc rat myotubes. Our findings suggest that CDDO-EA suppresses LPS-induced inflammation in macrophages and myocytes and that CDDO-EA is a promising compound as a therapeutic agent for protecting skeletal muscle from inflammation.
The novel Nrf2 activator CDDO-EA attenuates cerebral ischemic injury by promoting microglia/macrophage polarization toward M2 phenotype in mice
CNS Neurosci Ther 2021 Jan;27(1):82-91.PMID:33280237DOI:10.1111/cns.13496.
The aim of present study was to explore whether 2-cyano-3, 12-dioxooleana-1, 9-dien-28-oic acid (CDDO)-ethylamide (CDDO-EA) attenuates cerebral ischemic injury and its possible mechanisms using a middle cerebral artery occlusion (MCAO) model in C57BL/6 mice. Our results showed that intraperitoneal injection (i.p.) of CDDO-EA (2 and 4 mg/kg) augmented NFE2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression in ischemic cortex after MCAO. Moreover, CDDO-EA (2 mg/kg, i.p.) significantly enhanced Nrf2 nuclear accumulation, associated with increased cytosolic HO-1 expression, reduced neurological deficit and infarct volume as well as neural apoptosis, and shifted polarization of microglia/macrophages toward an antiinflammatory M2 phenotype in ischemic cortex after MCAO. Using an in vitro model, we confirmed that CDDO-EA (100 μg/mL) increased HO-1 expression and primed microglial polarization toward M2 phenotype under inflammatory stimulation in BV2 microglial cells. These findings suggest that a novel Nrf2 activator CDDO-EA confers neuroprotection against ischemic injury.
Effects of a 33-ion sequential beam galactic cosmic ray analog on male mouse behavior and evaluation of CDDO-EA as a radiation countermeasure
Behav Brain Res 2022 Feb 15;419:113677.PMID:34818568DOI:10.1016/j.bbr.2021.113677.
In long-term spaceflight, astronauts will face unique cognitive loads and social challenges which will be complicated by communication delays with Earth. It is important to understand the central nervous system (CNS) effects of deep spaceflight and the associated unavoidable exposure to galactic cosmic radiation (GCR). Rodent studies show single- or simple-particle combination exposure alters CNS endpoints, including hippocampal-dependent behavior. An even better Earth-based simulation of GCR is now available, consisting of a 33-beam (33-GCR) exposure. However, the effect of whole-body 33-GCR exposure on rodent behavior is unknown, and no 33-GCR CNS countermeasures have been tested. Here astronaut-age-equivalent (6mo-old) C57BL/6J male mice were exposed to 33-GCR (75cGy, a Mars mission dose). Pre-/during/post-Sham or 33-GCR exposure, mice received a diet containing a 'vehicle' formulation alone or with the antioxidant/anti-inflammatory compound CDDO-EA as a potential countermeasure. Behavioral testing beginning 4mo post-irradiation suggested radiation and diet did not affect measures of exploration/anxiety-like behaviors (open field, elevated plus maze) or recognition of a novel object. However, in 3-Chamber Social Interaction (3-CSI), CDDO-EA/33-GCR mice failed to spend more time exploring a holder containing a novel mouse vs. a novel object (empty holder), suggesting sociability deficits. Also, Vehicle/33-GCR and CDDO-EA/Sham mice failed to discriminate between a novel stranger vs. familiarized stranger mouse, suggesting blunted preference for social novelty. CDDO-EA given pre-/during/post-irradiation did not attenuate the 33-GCR-induced blunting of preference for social novelty. Future elucidation of the mechanisms underlying 33-GCR-induced blunting of preference for social novelty will improve risk analysis for astronauts which may in-turn improve countermeasures.
The Synthetic Triterpenoid RTA 405 (CDDO-EA) Halts Progression of Liver Fibrosis and Reduces Hepatocellular Carcinoma Size Resulting in Increased Survival in an Experimental Model of Chronic Liver Injury
Toxicol Sci 2016 Jan;149(1):111-20.PMID:26443840DOI:10.1093/toxsci/kfv213.
Patients with cirrhosis have an increased risk of developing liver cancer and a higher rate of mortality. Cirrhosis currently has no known cure, and patients may benefit from new agents aimed at alleviating their complications and slowing down the rate of disease progression. Therefore, the effects of the orally bioavailable synthetic triterpenoid 2-cyano-3,12-dioxooleana- 1,9(11)-dien-28-oate-ethyl amide (CDDO-EA, RTA 405), which has potent antioxidative and antiinflammatory properties, was evaluated in a chronic carbon tetrachloride (CCl(4))-induced model of liver cirrhosis and hepatocellular carcinoma (HCC). Mice were injected with CCl(4) (to induce fibrosis and cirrhosis) or placebo biweekly for 12 weeks followed by CDDO-EA in the diet for 18 weeks with continued biweekly injections of CCl(4). Chronic CCl(4) administration resulted in cirrhosis, ascites, and HCC formation, associated with increased serum transforming growth factor-β1, hepatic hydroxyproline content, and increased serum bilirubin. CDDO-EA, whose administration commenced after establishment of liver fibrosis, decreased liver fibrosis progression, serum bilirubin, ascites, and HCC formation and markedly increased overall survival. CDDO-EA also attenuated -TNFα (tumor necrosis factor-α), α-SMA (alpha smooth muscle actin), augmented -IL-10 levels, and improved histologic and serologic markers of fibrosis. Conclusions: CDDO-EA mitigates the progression of liver fibrosis induced by chronic CCl(4) administration, which is associated with the induction of antifibrogenic genes and suppression of profibrogenic genes.
Synthetic triterpenoids, CDDO-Imidazolide and CDDO-Ethyl amide, induce chondrogenesis
Osteoarthritis Cartilage 2012 May;20(5):446-450.PMID:22343171DOI:10.1016/j.joca.2012.01.018.
Novel methods for inducing chondrogenesis are critical for cartilage tissue engineering and regeneration. Here we show that the synthetic oleanane triterpenoids, CDDO-Imidazolide (CDDO-Im) and CDDO-Ethyl amide (CDDO-EA), at concentrations as low as 200 nM, induce chondrogenesis in organ cultures of newborn mouse calvaria. The cartilage phenotype was measured histologically with metachromatic toluidine blue staining for proteoglycans and by immunohistochemical staining for type II collagen. Furthermore, real-time polymerase chain reaction (PCR) analysis using mRNA from calvaria after 7-day treatment with CDDO-Im and CDDO-EA showed up-regulation of the chondrocyte markers SOX9 and type II collagen (alpha1). In addition, TGF-β; BMPs 2 and 4; Smads 3, 4, 6, and 7; and TIMPs-1 and -2 were increased. In contrast, MMP-9 was strongly down-regulated. Treatment of human bone marrow-derived mesenchymal stem cells with CDDO-Im and CDDO-EA (100 nM) induced expression of SOX9, collagen IIα1, and aggrecan, as well as BMP-2 and phospho-Smad5, confirming that the above triterpenoids induce chondrogenic differentiation. This is the first report of the use of these drugs for induction of chondrogenesis.