Rapamycin (Sirolimus)
(Synonyms: 雷帕霉素; 西罗莫司; Sirolimus; AY-22989) 目录号 : GC15031
Rapamycin曾经被用作抗真菌抗生素。
Cas No.:53123-88-9
Sample solution is provided at 25 µL, 10mM.
Rapamycin used to be used as an antifungal antibiotic[3]. Rapamycin exerts immunosuppressive effects by inhibiting the activation and proliferation of T cells. Rapamycin binds to FK-binding protein 12 (FKBP12) to form the Rapamycin-FKBP12 complex, which can inhibit mTOR[4,6].As a potent and specific mTOR inhibitor with an IC50?of 0.1 nM in HEK293 cells. Rapamycin binds to FKBP12 and specifically acts as an allosteric inhibitor of mTORC1[5].
Rapamycin (12.5-100 nM; 24 hours) treatment exerts modest inhibitory effect on lung cancer cell proliferation in a dose-dependent manner in all cell lines (A549, SPC-A-1, 95D and NCI-H446 cells) tested, achieving about 30-40% reduction in cell proliferation at 100 nM vs. ~10% reduction at 12.5 nM[7].Rapamycin potently not only suppressed proliferation but also induced the apoptosis of LECs in a dose-dependent manner under HGF administration. Rapamycin could promote apoptosis of LECs via inhibiting HGF-induced phosphorylation of AKT/mTOR, ERK and JAK2/STAT3 signaling molecules[1].
Rapamycin reduces neurologic disease in Ndufs4 -- / -- mice. In rapamycin treated knockout mice, the percentage of mice exhibiting neurological symptoms was greatly reduced at each age point after P35, and about half of these mice never showed obvious signs of neurological disease before dying[2]. Rapamycin alone has a moderate inhibitory effect. However, the combination of Metformin and Rapamycin exerts a significantly increased inhibition of tumor growth compared with the control group, the Rapamycin monotherapy group and the Metformin monotherapy group[8].Rapamycin treatment in cell culture significantly inhibits c-Myc-regulated gene expression. Rapamycin suppresses tumor growth along with a decreased expression of STAT3 and c-Myc in an in vivo xenograft mouse model for hepatocellular carcinoma[9].
References:
[1]: Tian F, Dong L, et,al. Rapamycin-Induced apoptosis in HGF-stimulated lens epithelial cells by AKT/mTOR, ERK and JAK2/STAT3 pathways. Int J Mol Sci. 2014 Aug 11;15(8):13833-48. doi: 10.3390/ijms150813833. PMID: 25116684; PMCID: PMC4159827.
[2]: Johnson SC, Yanos ME, et,al. mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome. Science. 2013 Dec 20;342(6165):1524-8. doi: 10.1126/science.1244360. Epub 2013 Nov 14. PMID: 24231806; PMCID: PMC4055856.
[3]: Sehgal SN, Baker H, et,al. Rapamycin (AY-22,989), a new antifungal antibiotic. II. Fermentation, isolation and characterization. J Antibiot (Tokyo). 1975 Oct;28(10):727-32. doi: 10.7164/antibiotics.28.727. PMID: 1102509.
[4]: Sehgal SN. Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clin Biochem. 1998 Jul;31(5):335-40. doi: 10.1016/s0009-9120(98)00045-9. PMID: 9721431.
[5]: Edwards SR, Wandless TJ. The rapamycin-binding domain of the protein kinase mammalian target of rapamycin is a destabilizing domain. J Biol Chem. 2007 May 4;282(18):13395-401. doi: 10.1074/jbc.M700498200. Epub 2007 Mar 9. PMID: 17350953; PMCID: PMC3763840.
[6]: Rangaraju S, Verrier JD, et,al. Rapamycin activates autophagy and improves myelination in explant cultures from neuropathic mice. J Neurosci. 2010 Aug 25;30(34):11388-97. doi: 10.1523/JNEUROSCI.1356-10.2010. PMID: 20739560; PMCID: PMC3478092.
[7]: Niu H, Wang J, et,al. Rapamycin potentiates cytotoxicity by docetaxel possibly through downregulation of Survivin in lung cancer cells. J Exp Clin Cancer Res. 2011 Mar 10;30(1):28. doi: 10.1186/1756-9966-30-28. PMID: 21392382; PMCID: PMC3065416.
[8]: Zhang JW, Zhao F, et,al. Metformin synergizes with rapamycin to inhibit the growth of pancreatic cancer in vitro and in vivo. Oncol Lett. 2018 Feb;15(2):1811-1816. doi: 10.3892/ol.2017.7444. Epub 2017 Nov 20. PMID: 29434877; PMCID: PMC5774390.
[9]: Sun L, Yan Y, et,al. Rapamycin targets STAT3 and impacts c-Myc to suppress tumor growth. Cell Chem Biol. 2022 Mar 17;29(3):373-385.e6. doi: 10.1016/j.chembiol.2021.10.006. Epub 2021 Oct 26. PMID: 34706270.
Rapamycin曾经被用作抗真菌抗生素。它通过抑制T细胞的激活和增殖来发挥免疫抑制作用。Rapamycin结合FK结合蛋白12（FKBP12）形成Rapamycin-FKBP12复合物,可以抑制mTOR。在HEK293细胞中,Rapamycin是一种有效而特异性的mTOR抑制剂,其IC50为0.1 nM。Rapamycin结合FKBP12并特异性地作为mTORC1的变构抑制剂。
在所有测试的细胞系（A549、SPC-A-1、95D和NCI-H446细胞）中,拉帕霉素（12.5-100 nM；24小时）治疗以剂量依赖性方式对肺癌细胞增殖产生适度的抑制作用,在100 nM时实现约30-40%的细胞增殖减少,而在12.5 nM时仅有约10%的减少。拉帕霉素不仅能有效地抑制增殖,还能以剂量依赖性方式诱导LEC的凋亡,在HGF管理下通过抑制AKT/mTOR、ERK和JAK2/STAT3信号分子的磷酸化来促进LEC的凋亡。
在Ndufs4 - / -小鼠中,雷帕霉素减少了神经疾病。在接受雷帕霉素治疗的敲除小鼠中,在P35后的每个年龄点上表现出神经症状的小鼠比例大大降低,并且其中约有一半的小鼠在死亡前从未显示出明显的神经疾病迹象[2]。单用雷帕霉素具有适度抑制作用。然而,二甲双胍和雷帕霉素联合使用与对照组、单用雷帕霉素组和单用二甲双胍组相比,能够显著增强肿瘤生长的抑制作用[8]。细胞培养中使用雷帕霉素可显著抑制c-Myc调节基因表达。在体内移植模型下,雷帕霉素通过降低STAT3和c-Myc表达来抑制肝细胞癌肿瘤生长[9]。
| Cell experiment [1]: | |
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Cell lines |
HGF-Treated Lens Epithelial Cells (LECs) |
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Preparation Method |
After pretreatment with HGF for 12 h, LEC was treated with increased doses of rapamycin (0, 1.5 and 10 ng/mL) at different time points (24, 48 and 72 h). |
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Reaction Conditions |
1/5/10 ng/mL for 24/48h/72h |
|
Applications |
Rapamycin inhibited the proliferation of lens epithelial cells (LEC) induced by hepatocyte growth factor (HGF) in a dose-and time-dependent manner. |
| Animal experiment [2]: | |
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Animal models |
Ndufs4 -- / -- mice |
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Preparation Method |
Rapamycin (8 mg/kg) was delivered by intraperitoneal injection every other day from weaning [approximately day 20 postpartum (P20)]. |
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Dosage form |
8 mg/kg, every other day, by intraperitoneal injection |
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Applications |
Rapamycin reduces neurologic disease in Ndufs4 -- / -- mice. |
|
References: [1]: Tian F, Dong L, et,al. Rapamycin-Induced apoptosis in HGF-stimulated lens epithelial cells by AKT/mTOR, ERK and JAK2/STAT3 pathways. Int J Mol Sci. 2014 Aug 11;15(8):13833-48. doi: 10.3390/ijms150813833. PMID: 25116684; PMCID: PMC4159827. |
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| Cas No. | 53123-88-9 | SDF | |
| 别名 | 雷帕霉素; 西罗莫司; Sirolimus; AY-22989 | ||
| Canonical SMILES | O[C@H]1[C@H](OC)C[C@H](C[C@@H](C)[C@H](CC([C@H](C)/C=C(C)/[C@H]([C@@H](OC)C([C@@H](C[C@@H](/C=C/C=C/C=C(C)/[C@@H](OC)C[C@@H]2CC[C@@H](C)[C@@](C(C(N3[C@H]4CCCC3)=O)=O)(O)O2)C)C)=O)O)=O)OC4=O)CC1 | ||
| 分子式 | C51H79NO13 | 分子量 | 914.18 |
| 溶解度 | ≥ 45.709mg/mL in DMSO, ≥ 58.9 mg/mL in EtOH with ultrasonic | 储存条件 | Desiccate 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 | 1.0939 mL | 5.4694 mL | 10.9388 mL |
| 5 mM | 0.2188 mL | 1.0939 mL | 2.1878 mL |
| 10 mM | 0.1094 mL | 0.5469 mL | 1.0939 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%
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