Everolimus (RAD001)
(Synonyms: 依维莫司; RAD001; SDZ-RAD) 目录号 : GC13601
依维莫司 (RAD001) 是一种具有口服活性的雷帕霉素衍生物，可抑制 Ser/Thr 激酶 mTOR（雷帕霉素的哺乳动物靶标）。
Cas No.:159351-69-6
Sample solution is provided at 25 µL, 10mM.
Everolimus (RAD001) is an orally active derivative of rapamycin that inhibits the Ser/Thr kinase, mTOR (mammalian target of rapamycin).[1]
In vitro activity of everolimus it displayed that the dose-dependent inhibition of cell growth by everolimus using methylene blue staining after 96 hours of incubation in four different human tumor cell lines, which can be regarded as sensitive (HCT-15, A549) and insensitive (KB-31 and HCT-116).[1] In vitro efficacy test, antiproliferative concentrations of RAD001 resulted in total dephosphorylation of S6K1 and the substrate S6 and a shift in the mobility of 4E-BP1, with IC50 of 0.7 nmol/L and 1,778 nmol/L in both the sensitive murine B16/BL6 melanoma and the insensitive human cervical KB-31,respectively.[2] In vitro study, combination gemcitabine (100 nM) with everolimus (0.05-2 μM) had significantly antiproliferative effect with an arrest of cell cycle at S phase.[3]
In vivo experimental it shown that everolimus is very well tolerated with no obvious clinical signs of toxicity; even when treating for up to 60 mg/kg per day by oral gavage the maximum tolerated dosage was not reached. In vivo efficacy study, daily orally treatment with everolimus (0.5 or 2.5 mg/kg) dose-dependently inhibited growth, and using a higher dose of 5 mg/kg once or twice per week also showed similar antitumor efficacy in the rat CA20498 model.[1] In vivo, treatment with 0.1-10 mg/kg/d RAD001 dose-dependently increased the hemoglobin content but reduced the Tie-2 content and this was significant for VEGF stimulation but not bFGF stimulation.[2]
References:
[1].O'Reilly T, McSheehy PM. Biomarker Development for the Clinical Activity of the mTOR Inhibitor Everolimus (RAD001): Processes, Limitations, and Further Proposals. Transl Oncol. 2010 Apr;3(2):65-79.
[2].Lane HA, et al. mTOR inhibitor RAD001 (everolimus) has antiangiogenic/vascular properties distinct from a VEGFR tyrosine kinase inhibitor. Clin Cancer Res. 2009 Mar 1;15(5):1612-22.
[3].Pinto-Leite R, et al. Everolimus enhances gemcitabine-induced cytotoxicity in bladder-cancer cell lines. J Toxicol Environ Health A. 2012;75(13-15):788-99.
依维莫司 (RAD001) 是一种具有口服活性的雷帕霉素衍生物,可抑制 Ser/Thr 激酶 mTOR（雷帕霉素的哺乳动物靶标）。[1]
依维莫司的体外活性显示,在四种不同的人类肿瘤细胞系中孵育 96 小时后,使用亚甲蓝染色依维莫司对细胞生长的剂量依赖性抑制,可视为敏感（HCT-15、A549 ) 和不敏感（KB-31 和 HCT-116）。[1]在体外功效测试中,抗增殖浓度的 RAD001 导致 S6K1 和底物 S6 的完全去磷酸化以及 4E-BP1 的迁移率发生变化,在敏感小鼠 B16/BL6 中的 IC50 分别为 0.7 nmol/L 和 1,778 nmol/L分别对黑色素瘤和不敏感的人宫颈 KB-31。[2] 体外研究表明,吉西他滨 (100 nM) 与依维莫司 (0.05-2 μM) 的组合具有显着的抗增殖作用,并可阻滞细胞周期在S期。[3]
体内实验表明,依维莫司的耐受性非常好,没有明显的临床毒性迹象；即使通过口服强饲法以每天高达 60 mg/kg 的剂量进行治疗,也未达到最大耐受剂量。体内功效研究表明,每日口服依维莫司（0.5 或 2.5 mg/kg）剂量依赖性地抑制生长,每周一次或两次使用更高剂量的 5 mg/kg 在大鼠 CA20498 模型中也显示出相似的抗肿瘤功效。 [1] 在体内,用 0.1-10 mg/kg/d RAD001 剂量依赖性地增加血红蛋白含量但降低 Tie-2 含量,这对 VEGF 刺激有显着意义,但对 bFGF 刺激没有意义。 [2]
| Cell experiment [1]: | |
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Cell lines |
MTC cell |
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Preparation Method |
The effects of everolimus and IGF-I on MTC cell viability in vitro were assessed by ATPlite assay on the Wallac Victor™ 1420 Multilabel Counter. Cells were treated after 24 h with or without 10 nM–1 μM everolimus and/or 50 nM IGF-I. Treatments were renewed after the first 24 h of incubation. Cell viability was assessed after 48 h. Results were obtained by determining the mean value of six replicates. |
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Reaction Conditions |
10 nM–1 μM, 24h |
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Applications |
Everolimus dose-dependently reduced cell viability, from –19% at 10 nM to –31% vs. control at 1 μM. In the E-NR MTCs, everolimus did not significantly modify cell viability. |
| Animal experiment [2]: | |
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Animal models |
5‐week‐old NOD/SCID mice |
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Preparation Method |
Everolimus or AZD8055 was dissolved in 30% (w/v) Captisol and given orally to mice at a dose of 5 mg/kg (everolimus) or 20 mg/kg (AZD8055) per day on weekdays from day 2 to day 20. The control mice received the vehicle only. |
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Dosage form |
5 mg/kg, p.o. |
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Applications |
AZD8055 more significantly inhibited the in vivo growth of the ATL‐cell xenografts than did everolimus. |
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References: [1]. Gentilin E, et al. Igf-I influences everolimus activity in medullary thyroid carcinoma. Front Endocrinol (Lausanne). 2015 May 5;6:63. [2].Kawata T, et al, Takaori-Kondo A. Dual inhibition of the mTORC1 and mTORC2 signaling pathways is a promising therapeutic target for adult T-cell leukemia. Cancer Sci. 2018 Jan;109(1):103-111. |
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| Cas No. | 159351-69-6 | SDF | |
| 别名 | 依维莫司; RAD001; SDZ-RAD | ||
| Canonical SMILES | OCCO[C@H]1[C@H](OC)C[C@H](C[C@H](C)[C@H](CC([C@H](C)/C=C(C)/[C@@H](O)[C@H]2OC)=O)OC([C@@H]3CCCCN3C(C([C@@]4(O)[C@H](C)CC[C@@H](C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C2=O)O4)=O)=O)=O)CC1 | ||
| 分子式 | C53H83NO14 | 分子量 | 958.22 |
| 溶解度 | ≥ 47.911mg/mL in DMSO, ≥ 122 mg/mL in EtOH | 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 | 1.0436 mL | 5.218 mL | 10.436 mL |
| 5 mM | 0.2087 mL | 1.0436 mL | 2.0872 mL |
| 10 mM | 0.1044 mL | 0.5218 mL | 1.0436 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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