Ridaforolimus (Deforolimus, MK-8669)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
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.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 990.21 |
| Cas No. | 572924-54-0 |
| Formula | C53H84NO14P |
| Solubility | ≥49.5mg/mL in DMSO |
| SDF | Download SDF |
| Canonical SMILES | O=P(C)(C)O[[email protected]]1[[email protected]](OC)C[[email protected]](C[[email protected]@H](C)[[email protected]@H](OC([[email protected]@H]2CCCCN2C(C([[email protected]]3([[email protected]@H](CC[[email protected]@H](C[[email protected]](OC)/C(C)=C/C=C/C=C/[[email protected]@H](C)C[[email protected]@H](C)C([[email protected]](OC)[[email protected]@H]4O)=O)O3)C)O)=O)=O)=O)CC([[email protected]](C)/C=C4\C)=O)CC1 |
| Shipping Condition | Evaluation sample solution: ship with blue ice. All other available sizes: ship with RT, or blue ice upon request. |
| General tips | For obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months. |
| Kinase experiment [1]: | |
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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. |
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Reacting condition |
100 nmol/L for 24-72 hours; or 10–100 nM for 24 h. |
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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 | |
Quality Control & MSDS
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Chemical structure
