Celastrol
(Synonyms: 雷公藤红素; Celastrol) 目录号 : GC15083
Celastrol是一种蛋白酶体抑制剂，有效且优先的抑制纯化的20S蛋白酶体，IC50 为2.5 μM。
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
| Cell experiment [1]: | |
Cell lines | Prostate cancer cell PC-3 |
Preparation Method | Prostate cancer cells were treated with Celastrol or Rubescensine A. The prepared whole cell extracts (30 μg per sample) were then incubated with 40 μM of Ac-DEVD-AMC in 100 μL assay buffer at 37°C for at least 2 hours. Afterwards, western blot was used for detection. |
Reaction Conditions | 2.5-5 μM, 1-12 h |
Applications | Celastrol concentration-dependently increased the levels of ubiquitinated proteins, and elevated levels of IκB-α, Bax, and p27 were also observed in PC-3 cells treated with Celastrol. |
| Animal experiment [1]: | |
Animal models | Human prostate tumor xenograft model |
Preparation Method | Fourteen days after mice were inoculated with PC-3 cells, they were intraperitoneally injected daily with 50 to 100 μL of vehicle [10% DMSO, 70% Cremophor/ethanol (3:1), and 20% PBS] and 1.0 or 3.0 mg/kg Celastrol. |
Dosage form | 1 or 3 mg/kg/day, 16 days, i.p. |
Applications | Celastrol at 1 or 3 mg/kg can significantly inhibit tumor growth, with inhibition rates of 65% and 82% respectively. |
| Kinase experiment [1]: | |
Preparation Method | 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 or Oridonin at different concentrations or in the solvent DMSO for 2 hours at 37°C, followed by measurement of inhibition of each proteasomal activity. |
Reaction Conditions | 0.1,1,10 and 100 μM, 2 h |
Applications | The chymotrypsin-like activity of the purified 20S proteasome was significantly inhibited by Celastrol with an IC50 value of 2.5 μM. |
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 proteasome inhibitor with a potent and preferred inhibition of purified 20S proteasome with an IC50 of 2.5 μM. Celastrol is also an antioxidant, anti-inflammatory agent, and immunosuppressant that can be used in the study of cancer, autoimmune diseases, asthma, chronic inflammation, and neurodegenerative diseases [1-2].
1-5 μM Celastrol inhibits the chymotrypsin-like activity of the 26S proteasome in human prostate cancer cells, and in PC-3 and LNCaP (androgen receptor-positive) cells, Celastrol leads to the accumulation of ubiquitinating proteins and proteasome substrates (IKB-A, Bax, and p27). And induce apoptosis [1]. Celastrol (0-1 μM) inhibited the proliferation and migration of AGS and YCC-2 cells and increased the number of cells in G1 phase [3]. In addition, Celastrol (0-10 μM) completely inhibits NF-κB activation in TNF-induced lung adenocarcinoma (H1299) cells and embryonic kidney (A293) cells, and Celastrol does not directly affect NF-κB binding to DNA, but inhibits NF-κB activation by inhibiting IKK activation [4].
In PC-3 tumor-bearing nude mice, Celastrol at 1 or 3 mg/kg significantly inhibited tumor growth, with inhibition rates of 65% and 82%, respectively, and a decrease in chymotrypsin-like activity was detected in the tumors of Celastrol-treated mice. (45% and 30% of the control group respectively) [1]. In a mouse model of gastric cancer xenotransplantation, Celastrol (1 or 2 mg/kg) reduced gastric tumor load in a dose-dependent manner, and Celastrol increased phosphorylated AMPK and decreased phosphorylated AKT and mTOR in gastric tumors [3].
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] Salminen A, Lehtonen M, Paimela T, et al. Celastrol: molecular targets of thunder god vine[J]. Biochemical and biophysical research communications, 2010, 394(3): 439-442.
[3] Lee HW, Jang KS, Choi HJ, Jo A, Cheong JH, Chun KH. Celastrol inhibits gastric cancer growth by induction of apoptosis and autophagy. BMB Rep. 2014 Dec;47(12):697-702.
[4] Sethi G, Ahn K S, Pandey M K, et al. Celastrol, a novel triterpene, potentiates TNF-induced apoptosis and suppresses invasion of tumor cells by inhibiting NF-κB–regulated gene products and TAK1-mediated NF-κB activation[J]. Blood, 2007, 109(7): 2727-2735.
Celastrol是一种蛋白酶体抑制剂，有效且优先的抑制纯化的20S蛋白酶体，IC50 为2.5 μM。Celastrol也是抗氧化剂、抗炎剂和免疫抑制剂，可用于癌症、自身免疫性疾病、哮喘、慢性炎症和神经退行性疾病的研究[1-2]。
1-5 μM的Celastrol可抑制人前列腺癌细胞26S蛋白酶体的糜蛋白酶样活性，并且在PC-3和LNCaP（雄激素受体阳性）细胞中，Celastrol导致泛素化蛋白和蛋白酶体底物（IKB-A、Bax和p27）的积累，并诱导细胞凋亡[1]。Celastrol（0-1 μM）抑制了AGS和YCC-2细胞的增殖、迁移并增加了G1期的细胞[3]。此外，Celastrol（0-10 μM）完全抑制TNF诱导的肺腺癌（H1299）细胞和胚胎肾（A293）细胞中的NF-κB活化，并且Celastrol不直接影响NF-κB与DNA的结合，而是通过抑制IKK激活来抑制NF-κB的激活[4]。
在PC-3荷瘤裸鼠中，1或3 mg/kg的Celastrol可显著抑制肿瘤生长，抑制率分别为65%和82%，并且Celastrol治疗的小鼠肿瘤中检测到糜蛋白酶样活性降低（分别为对照组的45%和30%）[1]。在胃癌异种移植小鼠模型中，Celastrol（1或2 mg/kg）以剂量依赖性方式减少胃肿瘤负荷，并且Celastrol增加了胃肿瘤中磷酸化的AMPK，减少了磷酸化的AKT和mTOR[3]。
| 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.