Celastrol
(Synonyms: 雷公藤红素; Celastrol) 目录号 : GC15083
A triterpenoid antioxidant
Cas No.:34157-83-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Kinase experiment [1]: | |
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Inhibition of purified 20S proteasome activity |
A purified rabbit 20S proteasome (0.1 μg) was incubated with 40 μM of various fluorogenic peptide substrates in 100 μL assay buffer (20 mM Tris-HCl (pH 7.5)), in the presence of Celastrol at different concentrations or in the solvent DMSO for 2 hrs at 37℃, followed by measurement of inhibition of each proteasomal activity. |
| Cell experiment [1]: | |
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Cell lines |
Androgen-independent PC-3 prostate cancer cells |
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Preparation method |
The solubility of this compound in DMSO is > 22.6 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
0.5 ~ 5 μM |
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Applications |
In PC-3 cells, Celastrol significantly inhibited the proteasomal chymotrypsin activity in a concentration-dependent manner. On the other hand, Celastrol concentration-dependently elevated the level of ubiquitinated proteins. Increased levels of IκB-α, Bax and p27 were also observed in PC-3 cells treated with Celastrol. |
| Animal experiment [1]: | |
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Animal models |
Nude mice bearing C4-2B tumors |
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Dosage form |
1 or 3 mg/kg/day; i.p.; for 16 days |
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Applications |
In nude mice bearing C4-2B tumors, Celastrol (3 mg/kg) significantly inhibited tumor growth (up to 70%), which was associated with increased p27 and Bax levels. Celastrol at the dose of 3 mg/kg also resulted in more apoptotic tumor cells with the appearance of various PARP cleavage fragments in xenograft tumors. In addition, Celastrol (3 mg/kg) caused 35% of tumor inhibition, which was correlated to decreased proteasome activity and down-regulated AR protein expression. |
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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. |
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References: [1]. Yang H, Chen D, Cui QC, et al. Celastrol, a triterpene extracted from the Chinese "Thunder of God Vine," is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. Cancer Res, 2006, 66(9): 4758-4765. | |
Celastrol is a potent proteasome inhibitor [1].Proteasomes are protein complexes that degrading unneeded or damaged proteins by proteolysis.
Celastrol is a potent proteasome inhibitor and an antioxidant, anti-inflammatory and immunosuppressive agent. In a cell-free proteasome activity assay, Celastrol inhibits the chymotrypsin-like activity of a purified rabbit 20S proteasome at 2.5umol and human prostate cancer cellular 26S proteasome at 1-5 μmol. In PC-3 and LNCaP (AR-positive) cells, Celastrol results in the accumulation of ubiquitinated proteins and proteasome substrates (IKB-A, Bax, and p27), and induction of apoptosis [1]. In KBM-5 cells, Celastrol enhances TNF-induced apoptosis by 2% to 92%. In the tumor cells, Celastrol inhibited TNF-induced tumor-cell invasion by 12-fold [2]. In human PBMCs, Celastrol inhibited LPS-induced TNF-α production with IC50 value of 70 nM and LPS-induced IL 113 production with IC50 value of 30nM in a dose-dependent way [3].
In PC-3 tumor–bearing nude mice, Celastrol (1-3 mg/kg/d,1-31 days) inhibited the tumor growth by 65-93% [1].
References:
[1]. Yang H, Chen D, Cui QC, et al. Celastrol, a triterpene extracted from the Chinese "Thunder of God Vine," is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. Cancer Res, 2006, 66(9): 4758-4765.
[2]. Allison AC, Cacabelos R, Lombardi VR, et al. Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry, 2001, 25(7):,1341-1357.
[3]. Sethi G, Ahn KS, Pandey MK, et al. Celastrol, a novel triterpene, potentiates TNF-induced apoptosis and suppresses invasion of tumor cells by inhibiting NF-kappaB-regulated gene products and TAK1-mediated NF-kappaB activation. Blood, 2007, 109(7): 2727-2735.
| Cas No. | 34157-83-0 | SDF | |
| 别名 | 雷公藤红素; Celastrol | ||
| 化学名 | (2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylic acid | ||
| Canonical SMILES | CC1=C(C(=O)C=C2C1=CC=C3C2(CCC4(C3(CCC5(C4CC(CC5)(C)C(=O)O)C)C)C)C)O | ||
| 分子式 | C29H38O4 | 分子量 | 450.61 |
| 溶解度 | ≥ 22.55mg/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 | 2.2192 mL | 11.0961 mL | 22.1921 mL |
| 5 mM | 0.4438 mL | 2.2192 mL | 4.4384 mL |
| 10 mM | 0.2219 mL | 1.1096 mL | 2.2192 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 | ||||||||||
| 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Celastrol Attenuates Angiotensin II-Induced Cardiac Remodeling by Targeting STAT3
Circ Res 2020 Apr 10;126(8):1007-1023.32098592 10.1161/CIRCRESAHA.119.315861
Rationale: Excessive Ang II (angiotensin II) levels lead to a profibrotic and hypertrophic milieu that produces deleterious remodeling and dysfunction in hypertension-associated heart failure. Agents that disrupt Ang II-induced cardiac dysfunction may have clinical utility in the treatment of hypertension-associated heart failure. Objective: We have examined the potential effect of celastrol-a bioactive compound derived from the Celastraceae family-on Ang II-induced cardiac dysfunction. Methods and results: In rat primary cardiomyocytes and H9C2 (rat cardiomyocyte-like H9C2) cells, Celastrol attenuates Ang II-induced cellular hypertrophy and fibrotic responses. Proteome microarrays, surface plasmon resonance, competitive binding assays, and molecular simulation were used to identify the molecular target of Celastrol. Our data showed that Celastrol directly binds to and inhibits STAT (signal transducer and activator of transcription)-3 phosphorylation and nuclear translocation. Functional tests demonstrated that the protection of Celastrol is afforded through targeting STAT3. Overexpression of STAT3 dampens the effect of Celastrol by partially rescuing STAT3 activity. Finally, we investigated the in vivo effect of Celastrol treatment in mice challenged with Ang II and in the transverse aortic constriction model. We show that Celastrol administration protected heart function in Ang II-challenged and transverse aortic constriction-challenged mice by inhibiting cardiac fibrosis and hypertrophy. Conclusions: Our studies show that Celastrol inhibits Ang II-induced cardiac dysfunction by inhibiting STAT3 activity.
Celastrol in metabolic diseases: Progress and application prospects
Pharmacol Res 2021 May;167:105572.33753246 10.1016/j.phrs.2021.105572
Metabolic diseases are becoming increasingly common in modern society. Therefore, it is essential to develop effective drugs or new treatments for metabolic diseases. As an active ingredient derived from plants, Celastrol has shown great potential in the treatment of a wide variety of metabolic diseases and received considerable attention in recent years. In reported studies, the anti-obesity effect of Celastrol resulted from regulating leptin sensitivity, energy metabolism, inflammation, lipid metabolism and even gut microbiota. Celastrol reversed insulin resistance via multiple routes to protect against type 2 diabetes. Celastrol also showed effects on atherosclerosis, cholestasis and osteoporosis. Celastrol in treating metabolic diseases seem to be versatile and the targets or pathways were diverse. Here, we systematically review the mechanism of action, and the therapeutic properties of Celastrol in various metabolic diseases and complications. Based on this review, potential research strategies might contribute to the Celastrol's clinical application in the future.
Treatment of obesity with Celastrol
Cell 2015 May 21;161(5):999-1011.26000480 PMC4768733
Despite all modern advances in medicine, an effective drug treatment of obesity has not been found yet. Discovery of leptin two decades ago created hopes for treatment of obesity. However, development of leptin resistance has been a big obstacle, mitigating a leptin-centric treatment of obesity. Here, by using in silico drug-screening methods, we discovered that Celastrol, a pentacyclic triterpene extracted from the roots of Tripterygium Wilfordi (thunder god vine) plant, is a powerful anti-obesity agent. Celastrol suppresses food intake, blocks reduction of energy expenditure, and leads to up to 45% weight loss in hyperleptinemic diet-induced obese (DIO) mice by increasing leptin sensitivity, but it is ineffective in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mouse models. These results indicate that Celastrol is a leptin sensitizer and a promising agent for the pharmacological treatment of obesity.
Celastrol induces ROS-mediated apoptosis via directly targeting peroxiredoxin-2 in gastric cancer cells
Theranostics 2020 Aug 15;10(22):10290-10308.32929349 PMC7481428
Background: Oxidative stress from elevated reactive oxygen species (ROS) has been reported to induce cell apoptosis and may provide a means to target cancer cells. Celastrol is a natural bioactive compound that was recently shown to increase ROS levels and cause apoptosis in cancer cells. However, the underlying mechanism for this cytotoxic action remains unclear and direct molecular targets of Celastrol have not been identified. Methods: Proteome microarray, surface plasmon resonance, isothermal titration calorimetry and molecular simulation were used to identify the molecular target of Celastrol. Binding and activity assays were used to validate the interaction of Celastrol with target protein in cell-free and gastric cancer cell lysates. We then assessed target transcript levels in in biopsy specimens obtained from patients with gastric cancer. Gastric cancer growth-limiting and cytotoxic activity of Celastrol was evaluated in BALB/c nu/nu mice. Results: Our data show that Celastrol directly binds to an antioxidant enzyme, peroxiredoxin-2 (Prdx2), which then inhibits its enzyme activity at both molecular and cellular level. Inhibition of Prdx2 by Celastrol increased cellular ROS levels and led to ROS-dependent endoplasmic reticulum stress, mitochondrial dysfunction, and apoptosis in gastric cancer cells. Functional tests demonstrated that Celastrol limits gastric cancer cells, at least in part, through targeting Prdx2. Celastrol treatment of mice implanted with gastric cancer cells also inhibited tumor growth, associated with Prdx2 inhibition and increased ROS. Analysis of human gastric cancer also showed increased Prdx2 levels and correlation with survival. Conclusion: Our studies have uncovered a potential Celastrol-interacting protein Prdx2 and a ROS-dependent mechanism of its action. The findings also highlight Prdx2 as a potential target for the treatment of gastric cancer.
The Nrf2-NLRP3-caspase-1 axis mediates the neuroprotective effects of Celastrol in Parkinson's disease
Redox Biol 2021 Nov;47:102134.34600334 PMC8487081
Parkinson's disease (PD) is a chronic neurodegenerative disorder that is characterized by motor symptoms as a result of a loss of dopaminergic neurons in the substantia nigra pars compacta (SNc), accompanied by chronic neuroinflammation, oxidative stress, formation of 伪-synuclein aggregates. Celastrol, a potent anti-inflammatory and anti-oxidative pentacyclic triterpene, has emerged as a neuroprotective agent. However, the mechanisms by which Celastrol is neuroprotective in PD remain elusive. Here we show that Celastrol protects against dopamine neuron loss, mitigates neuroinflammation, and relieves motor deficits in MPTP-induced PD mouse model and AAV-mediated human 伪-synuclein overexpression PD model. Whole-genome deep sequencing analysis revealed that Nrf2, NLRP3 and caspase-1 in SNc may be associated with the neuroprotective actions of Celastrol in PD. By using multiple genetically modified mice (Nrf2-KO, NLRP3-KO and Caspase-1-KO), we identified that Celastrol inhibits NLRP3 inflammasome activation, relieves motor deficits and nigrostriatal dopaminergic degeneration through Nrf2-NLRP3-caspase-1 pathway. Taken together, these findings suggest that Nrf2-NLRP3-caspase-1 axis may serve as a key target of Celastrol in PD treatment, and highlight the favorable properties of Celastrol for neuroprotection, making Celastrol as a promising disease-modifying agent for PD.