Oridonin
(Synonyms: 冬凌草甲素; NSC-250682; Isodonol) 目录号 : GN10692
冬凌草甲素（Oridonin）是蛋白激酶B（AKT；PKB）的抑制剂，对 AKT1和 AKT2的 IC50 值分别为8.4和8.9μM。
Cas No.:28957-04-2
Sample solution is provided at 25 µL, 10mM.
Oridonin is an inhibitor of protein kinase B (AKT; PKB), with IC50 values of 8.4 and 8.9μM for AKT1 and AKT2 respectively [1]. Oridonin preferentially blocks AKT kinase activity by inhibiting the phosphorylation of AKT substrates, thereby inhibiting downstream mTOR signaling [2]. Oridonin is also a high-affinity NLRP3 inflammasome inhibitor. Oridonin A can also inhibit NF-κB or MAPK activation [3].
In vitro, oridonin (1μM) treated breast cancer cell lines for three weeks, selectively inhibited the clonal growth of p-AKT High (MDAMB468, SKBR3 and HCC1569) cells but not p-AKT low (MDAMB231 and MCF- 10A) cells[2]. Incubation of A431 cells with oridonin (5, 20, 40 or 80 μM) resulted in a significant increase in cell death in a dose-dependent manner, inhibited total tyrosine kinase activity, and downregulated EGFR expression or EGFR phosphorylation [4]. Oridonin (5, 10, 20 μM) incubated OSCC cells dose-dependently led to cell apoptosis and induced cell cycle arrest in the G2/M phase [5].
In vivo, oral treatment of oridonin (160 mg/kg) in SCID mice transplanted with EG9 and HEG18 tumor cells significantly inhibited tumor growth without causing weight loss[1]. Oridonin (20 mg/kg), through intraperitoneal injection, significantly reduced the production of IL-1β in the joint tissue of wild-type C57BL/6 mice and alleviated acute joint swelling[3]. Intraperitoneal injection of oridonin (15 mg/kg) in xenograft mice inhibited the growth of colon cancer cells, significantly down-regulated the protein levels of GLUT1 and MCT1, inhibited glucose uptake and reduced lactate output, thereby inducing metabolic imbalance [6] .
References:
[1] Song M , Liu X , Liu K ,et al.Targeting AKT with oridonin inhibits growth of esophageal squamous cell carcinoma in vitro and patient derived xenografts in vivo[J].Molecular Cancer Therapeutics, 2018.
[2] Sun B, Wang G, Liu H, et al. Oridonin inhibits aberrant AKT activation in breast cancer[J]. Oncotarget, 2018, 9(35): 23878.
[3] He H, Jiang H, Chen Y, et al. Oridonin is a covalent NLRP3 inhibitor with strong anti-inflammasome activity[J]. Nature communications, 2018, 9(1): 2550.
[4] Li D , Wu L J , Tashiro S I , et al.Oridonin Inhibited the Tyrosine Kinase Activity and Induced Apoptosis in Human Epidermoid Carcinoma A431 Cells[J].Biological & Pharmaceutical Bulletin, 2007, 30(2):254-260.
[5] Wang H, Zhu L, Feng X, et al. Oridonin induces G2/M cell cycle arrest and apoptosis in human oral squamous cell carcinoma[J]. European Journal of Pharmacology, 2017, 815: 282-289.
[6]Yao Z, Xie F, Li M, et al. Oridonin induces autophagy via inhibition of glucose metabolism in p53-mutated colorectal cancer cells[J]. Cell death & disease, 2017, 8(2): e2633-e2633.
冬凌草甲素（Oridonin）是蛋白激酶B（AKT；PKB）的抑制剂，对 AKT1和 AKT2的 IC50 值分别为8.4和8.9μM[1]。冬凌草甲素通过抑制AKT底物的磷酸化优先阻断AKT激酶活性，从而抑制下游mTOR信号传导[2]。冬凌草甲素也是一种高亲和力NLRP3炎性体抑制剂，冬凌草甲素还可抑制NF-κB或MAPK激活[3]。
在体外，冬凌草甲素（1μM）处理乳腺癌细胞系三周，选择性抑制p-AKT High （MDAMB468，SKBR3和HCC1569）细胞的克隆生长，但不抑制p-AKT low （MDAMB231和MCF-10A）细胞[2]。冬凌草甲素（5, 20, 40 or 80μM）孵育A431细胞，剂量依赖性地导致细胞死亡率显著增加，抑制了总酪氨酸激酶活性，并下调EGFR表达或EGFR磷酸化[4]。冬凌草甲素（5, 10, 20μM）孵育OSCC细胞，剂量依赖性地导致细胞凋亡，诱导细胞周期停滞在G2/M期[5]。
在体内，冬凌草甲素（160mg/kg）口服治疗移植EG9和HEG18肿瘤细胞的SCID小鼠，显著抑制了肿瘤生长，且没有造成体重减轻[1]。冬凌草甲素（20mg/kg）通过腹腔注射，显著减少了野生型C57BL/6小鼠关节组织中IL-1β的产生，减轻了急性关节肿胀[3]。冬凌草甲素（15mg/kg）腹腔注射治疗异种移植小鼠，抑制结肠癌细胞的生长，显着下调GLUT1和MCT1的蛋白水平，抑制葡萄糖摄取并减少乳酸输出，从而诱导代谢失衡[6]。
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Kinase experiment [1]: |
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Preparation method |
For the AKT kinase assay, we used the ADP-Glo Kinase Assay Kit. Active AKT1 or AKT2 kinase and inactive GSK-3β as substrate were mixed by 1× reaction buffer and then added to a white 96-well plate. Pure ATP provided in the kit was serially diluted obtain a final concentration of 0, 1, 10, 50, and 100 μmol/L. Oridonin was added to reach a final concentration of 2.5, 5, 10, or 20μmol/L and DMSO was used as a control. |
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Reaction Conditions |
2.5, 5, 10, or 20μmol/L |
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Applications |
The IC50 of oridonin against AKT1 and AKT2 kinase activity was 8.4±1.34 and 8.9±0.92 μmol/L, respectively. |
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Cell experiment [2]: |
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Cell lines |
A431 cells |
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Preparation method |
A431 cells were incubated at 3 x 104 cells per well in 96-well plates. Then the cells were treated with oridonin at various doses (5, 20, 40 or 80μM) for 6, 12, 24 or 36 h. Cell growth was measured with a plate reader by MTT. |
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Reaction Conditions |
5, 20, 40 or 80μM; 6, 12, 24 or 36 h |
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Applications |
Incubation of A431 cells by different doses of oridonin (5, 20, 40 or 80μM) for different time periods (6, 12, 24 or 36 h) resulted in a significant increase in the death rate. |
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Animal experiment [3]: |
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Animal models |
C57BL/6 mice |
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Preparation method |
mice were used to induce peritonitis by intraperitoneal administration of 1 mg MSU crystals. Before injection of MSU, 20 mg/kg Oridonin were injected intraperitoneally. After 6 h, the mice were killed and 10 ml ice-cold PBS were used to wash the peritoneal cavities. The IL-1β level in serum or peritoneal lavage fluid was determined by ELISA. |
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Dosage form |
20mg/kg; i.p. |
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Applications |
Oridonin treatment prevented MSU injection induced acute joint swelling and IL-1β production in joint tissue of mice. |
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References: [1] Song M , Liu X , Liu K ,et al.Targeting AKT with oridonin inhibits growth of esophageal squamous cell carcinoma in vitro and patient derived xenografts in vivo[J].Molecular Cancer Therapeutics, 2018. [2] Li D , Wu L J , Tashiro S I , et al.Oridonin Inhibited the Tyrosine Kinase Activity and Induced Apoptosis in Human Epidermoid Carcinoma A431 Cells[J].Biological & Pharmaceutical Bulletin, 2007, 30(2):254-260. [3]He H, Jiang H, Chen Y, et al. Oridonin is a covalent NLRP3 inhibitor with strong anti-inflammasome activity[J]. Nature communications, 2018, 9(1): 2550. |
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| Cas No. | 28957-04-2 | SDF | |
| 别名 | 冬凌草甲素; NSC-250682; Isodonol | ||
| 化学名 | (1S,5S,6aS,9S,11bR)-1,5,6,14-tetrahydroxy-4,4-dimethyl-8-methylenedecahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-7(8H)-one | ||
| Canonical SMILES | O=C1[C@@](C(O[H])2OC3([H])[H])(C4([H])O[H])C(C([H])([H])C([H])([H])[C@@]4([H])/C1=C([H])/[H])([H])[C@@]35C(C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])[C@]5([H])O[H])([H])[C@]2([H])O[H] | ||
| 分子式 | C20H28O6 | 分子量 | 364.43 |
| 溶解度 | ≥ 13.6mg/mL in DMSO | 储存条件 | Store at -20°C, protect from light |
| 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 | 2.744 mL | 13.7201 mL | 27.4401 mL |
| 5 mM | 0.5488 mL | 2.744 mL | 5.488 mL |
| 10 mM | 0.2744 mL | 1.372 mL | 2.744 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。
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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