Ridaforolimus (Deforolimus, MK-8669)
(Synonyms: 42-(二甲基亚膦酰)雷帕霉素,MK-8669; Deforolimus; AP23573) 目录号 : GC13071
A rapamycin analog that selectively inhibits mTOR in mTORC1
Cas No.:572924-54-0
Sample solution is provided at 25 µL, 10mM.
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Ridaforolimus (Deforolimus, MK-8669), a novel rapamycin analogue, is a novel, potent and selective inhibitor of mTOR with IC50 value of 0.2nM [1].
HT-1080 fibrosarcoma cells treated with ridaforolimus have been demonstrated to dose-dependently inhibit S6 and 4E-BP1 phosphorylation with IC50 values of 0.2 and 5.6 nM, respectively, and EC50 values of 0.2 and 1.0 nM, respectively. The antiproliferative activity of ridaforolimus has been observed in a broad panel of cell lines including the colon cancer cells HCT-116, leiomyosarcoma cells SK-UT-1, etc. Ridaforolimus has shown to block the production of VEGF production dose-dependently, with an EC50 value of 0.1nM [1].
In vivo, mice bearing MCF7 (breast), PC-3 (prostate), A549 (lung), HCT-116 (colon) or PANC-1 (pancreas) xenografts have revealed the antitumor efficacy of ridaforolimus [1].
References:
[1] Rivera VM1, Squillace RM, Miller D, Berk L, Wardwell SD, Ning Y, Pollock R, Narasimhan NI, Iuliucci JD, Wang F, Clackson T.Ridaforolimus (AP23573; MK-8669), a potent mTOR inhibitor, has broad antitumor activity and can be optimally administered using intermittent dosing regimens. Mol Cancer Ther. 2011 Jun;10(6):1059-71.
| Kinase experiment [1]: | |
|
Cell based target inhibition |
HT-1080 cells are treated with increasing concentrations of Deforolimus (0-100 nM) for 2 hours, prior to harvest. Cellular lysates are extracted in denaturing lysis buffer, resolved on SDS-PAGE and transferred to PVDF membranes. After blocking, membranes are incubated with primary antibodies for 1 hour, followed by appropriate HRP-conjugated secondary antibodies for 1 hour at room temperature. Immunoreactive proteins are detected using enhanced chemiluminescence and autoradiography performed by exposure to X-ray film. IC50 is determined from the inhibition of levels of phosphorylated ribosomal protein S6 (p-S6) and 4E-BP1 (p-4E-BP1). |
| Cell experiment: | |
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Cell lines |
HCT-116, SK-UT-1, HT-1080, SW872, MCF7, SK-LMS-1, U-87, A-204, PC-3, Endothelial cells, SK-UT-1B, ARK1 and ARK2 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
100 nmol/L for 24-72 hours; or 10–100 nM for 24 h. |
|
Applications |
Ridaforolimus showed the broad inhibitory effects on cell growth, division, metabolism, and angiogenesis and attenuated mTOR signaling [1]. Moreover, Ridaforolimus (20–100 nM) treatment decreased the viability in ARK1 and ARK2 cells [2]. |
| Animal experiment: | |
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Animal models |
Female C57bl/6 and BALB/c mice model; male and female athymic NCr-nu mice model; mice harboring uterine serous carcinoma (USC) xenografts |
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Dosage form |
3 or 10 mg/kg, i.p. daily for 5 days every other week or once weekly for 20 days; or 1 mg/kg, i.p. for 22 days |
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Applications |
Ridaforolimus induced tumor growth inhibition in mice bearing PC-3 (prostate), HCT-116 (colon), MCF7 (breast), PANC-1 (pancreas), SK-LMS-1 (sarcoma) or A549 (lung) xenografts [1]. Moreover, Ridaforolimus improved the anti-tumor activity of dual HER2 blockade in mice harboring uterine serous carcinoma (USC) xenografts [2]. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: 1. Rivera, V. M., Squillace, R. M., Miller, D., Berk, L., Wardwell, S. D., Ning, Y., Pollock, R., Narasimhan, N. I., Iuliucci, J. D., Wang, F. and Clackson, T. (2011) Ridaforolimus (AP23573; MK-8669), a potent mTOR inhibitor, has broad antitumor activity and can be optimally administered using intermittent dosing regimens. Mol Cancer Ther. 10, 1059-1071 2. Hernandez, S. F., Chisholm, S., Borger, D., Foster, R., Rueda, B. R. and Growdon, W. B. (2016) Ridaforolimus improves the anti-tumor activity of dual HER2 blockade in uterine serous carcinoma in vivo models with HER2 gene amplification and PIK3CA mutation. Gynecol Oncol. 141, 570-579 |
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| Cas No. | 572924-54-0 | SDF | |
| 别名 | 42-(二甲基亚膦酰)雷帕霉素,MK-8669; Deforolimus; AP23573 | ||
| Canonical SMILES | O=P(C)(C)O[C@H]1[C@H](OC)C[C@H](C[C@@H](C)[C@@H](OC([C@@H]2CCCCN2C(C([C@]3([C@@H](CC[C@@H](C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C([C@H](OC)[C@@H]4O)=O)O3)C)O)=O)=O)=O)CC([C@H](C)/C=C4\C)=O)CC1 | ||
| 分子式 | C53H84NO14P | 分子量 | 990.21 |
| 溶解度 | ≥ 49.5mg/mL in DMSO | 储存条件 | Store at -20°C,unstable in solution, ready to use. |
| 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 | 1.0099 mL | 5.0494 mL | 10.0989 mL |
| 5 mM | 0.202 mL | 1.0099 mL | 2.0198 mL |
| 10 mM | 0.101 mL | 0.5049 mL | 1.0099 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
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet