Ridaforolimus (Deforolimus, MK-8669)
For research use only. Not for use in humans.
Catalog No.S1022 Synonyms: AP23573
11 publications
Molecular Weight(MW): 990.21
Ridaforolimus (Deforolimus, MK-8669) is a selective mTOR inhibitor with IC50 of 0.2 nM in HT-1080 cell line; while not classified as a prodrug, mTOR inhibition and FKBP12 binding is similar to rapamycin. Phase 3.
2 Customer Reviews
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Breast cancer cells were pretreated with 100ng/ml EGF for 15 min and then treated with the indicated concentrations of Deforolimus for 24 hours.
Dr. Zhang of Tianjin Medical University. Ridaforolimus (Deforolimus, MK-8669) purchased from Selleck.
Protein analysis of ARK1 and ARK2 (A) xenografts following acute therapy with vehicle, ridaforolimus, lapatinib and trastuzumab or the triple combination.
Gynecol Oncol, 2016, 141(3):570-9. Ridaforolimus (Deforolimus, MK-8669) purchased from Selleck.
Purity & Quality Control
Choose Selective mTOR Inhibitors
Biological Activity
| Description | Ridaforolimus (Deforolimus, MK-8669) is a selective mTOR inhibitor with IC50 of 0.2 nM in HT-1080 cell line; while not classified as a prodrug, mTOR inhibition and FKBP12 binding is similar to rapamycin. Phase 3. | ||
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| Targets |
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| In vitro |
Treatment of HT-1080 cells with Deforolimus induces a dose-dependent inhibition of phosphorylation of both S6 and 4E-BP1, with IC50 of 0.2 nM and 5.6 nM, respectively, and leads to a decrease in cell size, an increase in the proportion of cells in the G1 phase of the cell cycle, and inhibition of glucose uptake. Deforolimus displays significant antiproliferative activity a broad panel of cell lines with EC50 of 0.2-2.3 nM. Deforolimus potently and selectively inhibits VEGF production in a dose-dependent manner. [1] Deforolimus treatment significantly induces growth suppression in human NSCLC cell lines with IC30 values of 2.45-8.83 nM, with the exception of H157 with IC30 of >20 nM. Deforolimus treatment (2.8-5.9 nM) significantly dephosphorylates p70S6KThr389 in A549, H1703 and H157 cells, except H1666 that may express a resistant variant of mTORC1, and causes increased phosphorylation of pAKTser473 and pAKTThr308 in A549 and H1703 cells. Deforolimus in combination with the MEK inhibitors, CI-1040 or PD0325901 exhibits dose-dependent synergism in lung cancer cell lines, which is associated with the suppression of proliferation rather than enhancement of cell death, involving the inhibition of ribosomal biogenesis by 40% within 24 hours and a decreased polysome/monosome ratio. [2] |
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| In vivo | Administration of Deforolimus exerts significant antitumor effects in mice bearing PC-3 (prostate), HCT-116 (colon), MCF7 (breast), PANC-1 (pancreas) or A549 (lung) xenografts in a dose-dependent manner, and inhibits mTOR signaling in in SK-LMS-1 xenograft model associated with inhibition of tumor growth. [1] |
Protocol
| Kinase Assay:[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 HRPconjugated 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). |
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| Cell Research:[2] |
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| Animal Research:[1] |
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Solubility (25°C)
| In vitro | DMSO | 198 mg/mL (199.95 mM) |
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| Water | Insoluble | |
| Ethanol | Insoluble | |
| In vivo | Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 4% Ethanol+5% Tween 80+5% propylene glycol For best results, use promptly after mixing. |
5mg/mL |
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Information
| Molecular Weight | 990.21 |
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| Formula | C53H84NO14P |
| CAS No. | 572924-54-0 |
| Storage | powder |
| in solvent | |
| Synonyms | AP23573 |
| Smiles | COC1CC(CCC1O[P](C)(C)=O)CC(C)C2CC(=O)C(C)\C=C(C)\C(O)C(OC)C(=O)C(C)CC(C)/C=C/C=C/C=C(C)/C(CC3CCC(C)C(O)(O3)C(=O)C(=O)N4CCCCC4C(=O)O2)OC |
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Clinical Trial Information
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|---|
| NCT01431547 | Completed | Drug: dalotuzumab|Drug: ridaforolimus | Solid Tumors | Merck Sharp & Dohme Corp. | February 2012 | Phase 1 |
| NCT01431534 | Terminated | Drug: Ridaforolimus | Solid Tumors | Merck Sharp & Dohme Corp. | January 30 2012 | Phase 1 |
| NCT01380184 | Completed | Drug: ridaforolimus | Cancer Advanced | Merck Sharp & Dohme Corp. | July 5 2011 | Phase 1 |
| NCT01295632 | Completed | Drug: ridaforolimus|Drug: MK-0752|Drug: MK-2206 | Advanced Cancer | Merck Sharp & Dohme Corp. | February 2011 | Phase 1 |
| NCT01212627 | Terminated | Drug: Ridaforolimus | Non-Small Cell Lung Cancer | Angela Taber MD|Rhode Island Hospital|The Miriam Hospital|Memorial Hospital of Rhode Island|Roger Williams Medical Center|Brown University | September 2010 | Phase 1 |
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