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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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]。
| 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. | |
| 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。
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Quality Control & SDS
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- Purity: >99.50%
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