Rapamycin (Sirolimus) Licensed by Pfizer

Catalog No.S1039
5 5 34 Product Citations

Rapamycin (Sirolimus, AY-22989, WY-090217) is a specific mTOR inhibitor with IC50 of ~0.1 nM.

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Rapamycin (Sirolimus) Chemical Structure

Rapamycin (Sirolimus) Chemical Structure
Molecular Weight: 914.18

Validation & Quality Control

Product Citations(34)

Customer Reviews(9)

Quality Control & MSDS

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Product Description

Biological Activity

Description Rapamycin (Sirolimus, AY-22989, WY-090217) is a specific mTOR inhibitor with IC50 of ~0.1 nM.
Targets mTOR [1]
IC50 ~0.1 nM
In vitro Rapamycin inhibits endogenous mTOR activity in HEK293 cells with IC50 of ~0.1 nM, more potently than iRap and AP21967 with IC50 of ~5 nM and ~10 nM, respectively. [1] In Saccharomyces cerevisiae, Rapamycin treatment induces a severe G1/S cell cycle arrest and inhibition of translation initiation to levels below 20% of control. [2] Rapamycin significantly inhibits the cell viability of T98G and U87-MG in a dose-dependent manner with IC50 of 2 nM and 1 μM, respectively, while displaying little activity against U373-MG cells with IC50 of >25 μM despite the similar extent of the inhibition of mTOR signaling. Rapamycin (100 nM) induces G1 arrest and autophagy but not apoptosis in Rapamycin-sensitive U87-MG and T98G cells by inhibiting the function of mTOR. [3]
In vivo Treatment with Rapamycin in vivo specifically blocks targets known to be downstream of mTOR such as the phosphorylation and activation of p70S6K and the release of inhibition of eIF4E by PHAS-1/4E-BP1, leading to complete blockage of the hypertrophic increases in plantaris muscle weight and fibre size. [4] Short-term Rapamycin treatment, even at the lowest dose of 0.16 mg/kg, produces profound inhibition of p70S6K activity, which correlates with increased tumor cell death and necrosis of the Eker renal tumors. [5] Rapamycin inhibits metastatic tumor growth and angiogenesis in CT-26 xenograft models by reducing the production of VEGF and blockage of VEGF-induced endothelial cell signaling. [6] Rapamycin treatment at 4 mg/kg/day significantly reduces tumor growth of C6 xenografts, and tumor vascular permeability. [7]
Features

Protocol(Only for Reference)

Kinase Assay:

[1]

Immunoblotting for the mTOR kinase assay HEK293 cells are plated at 2-2.5×105 cells/well of a 12-well plate and serum-starved for 24 hours in DMEM. Cells are treated with increasing concentrations of Rapamycin (0.05-50 nM) for 15 minutes at 37 °C. Serum is added to a final concentration of 20% for 30 minutes at 37 °C. Cells are lysed, and cell lysates are separated by SDS-PAGE. Resolved proteins are transferred to a polyvinylidene difluoride membrane and immunoblotted with a phosphospecific primary antibody against Thr-389 of p70 S6 kinase. Data are analyzed using ImageQuant and KaleidaGr

Cell Assay:

[3]

Cell lines U87-MG, T98G, and U373-MG
Concentrations Dissolved in DMSO, final concentrations ~25 μM
Incubation Time 72 hours
Method

Cells are exposed to various concentrations of Rapamycin for 72 hours. For the assessment of cell viability, cells are collected by trypsinization, stained with trypan blue, and the viable cells in each well are counted. For the determination of cell cycle, cells are trypsinized, fixed with 70% ethanol, and stained with propidium iodide using a flow cytometry reagent set. Samples are analyzed for DNA content using a FACScan flow cytometer and CellQuest software. For apoptosis detection, cells are stained with the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) technique using an ApopTag apoptosis detection kit. To detect the development of acidic vesicular organelles (AVO), cells are stained with acridine orange (1 μg/mL) for 15 minutes, and examined under a fluorescence microscope. To quantify the development of AVOs, cells are stained with acridine orange (1 μg/mL) for 15 minutes, removed from the plate with trypsin-EDTA, and analyzed using the FACScan flow cytometer and CellQuest software. To analyze the autophagic process, cells are incubated for 10 minutes with 0.05 mM monodansylcadaverine at 37 °C and are then observed under a fluorescence microscope.

Animal Study:

[7]

Animal Models Athymic Nu/Nu mice inoculated subcutaneously with VEGF-A-expressing C6 rat glioma cells
Formulation Dissolved in solvent solution (0.2% carboxymethylcellulose and 0.25% Tween-80 in sterile H2O)
Dosages ~4 mg/kg/day
Administration Injection i.p.
Solubility 0.5% CMC/0.25% Tween 80, 30 mg/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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Edwards SR, et al. J Biol Chem, 2007, 282(18), 13395-13401.

[2] Barbet NC, et al. Mol Biol Cell, 1996, 7(1), 25-42.

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Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2014-10-24)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02042326 Not yet recruiting Arteriovenous Malformations (Stage II to IV) Centre Hospitalier Universitaire, Amiens January 2015 Phase 2
NCT02240407 Not yet recruiting Pompe Disease University of Florida October 2014 Phase 1
NCT02238496 Recruiting Brain Tumor, Recurrent|Glioblastoma|Anaplastic Astrocytoma|Anaplastic Oligodendroglioma|Mixed Glioma Andrew Lassman|Pfizer|AEterna Zentaris|Columbia University July 2014 Phase 2
NCT02177760 Recruiting Severe Combined Immunodeficiency|Transplacental Maternal Engraftment|Stem Cell Transplant University of California, San Francisco July 2014 Phase 2
NCT02214706 Recruiting Port-Wine Stain Erasmus Medical Center July 2014 --

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Chemical Information

Download Rapamycin (Sirolimus) SDF
Molecular Weight (MW) 914.18
Formula

C51H79NO13

CAS No. 53123-88-9
Storage 3 years -20℃Powder
6 months-80℃in DMSO
Synonyms
Solubility (25°C) * In vitro DMSO 20 mg/mL (21 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 0.5% CMC/0.25% Tween 80 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* 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 Name (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-Hexadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone

Research Area

Customer Reviews (9)


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Rating
Source Nat Genet 2014 46(4):364-70. Rapamycin (Sirolimus) purchased from Selleck
Method Western blot
Cell Lines Persister cells
Concentrations 10 nM
Incubation Time 3 days
Results While added with a specific mTOR inhibitor, rapamycin(Rapa), it inhibitied endogenous mTOR activity, showed that markedly reduced MYC protein levels in persister cells but not in naive T-ALL cells.

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Rating
Source Cancer Cell 2011 19, 1–13. Rapamycin (Sirolimus) purchased from Selleck
Method Cell viability Analysis
Cell Lines Ar+murine (CaP8) and human (LNCaP) prostate cancer cells, Pb-Cre+;PtenL/L mice, Pb-Cre+;PtenL/L;ArL/Y mice
Concentrations 1 nM, 4 mg/kg
Incubation Time 0-4 weeks
Results These data suggest that CaPs with AR loss have greater reliance upon the PI3K/AKT/mTOR-signaling pathways and that combined AR/androgen blockage in conjunction with PI3K/AKT/mTOR inhibition (by Rapamycin) is more effective for CaPs initiated by PTEN loss or PI3K/AKT activation.

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Rating
Source Cell Res 2012 22(6):1003-21. Rapamycin (Sirolimus) purchased from Selleck
Method EdU labeling
Cell Lines MCF-7 cells
Concentrations 150 nM
Incubation Time 48 h
Results The punctate structures from SRC-3 or MIF knockdown cells are very similar to that found in cells treated with rapamycin, a known inducer of autophagy.

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Rating
Source J Lipid Res 2011 52, 1617-1625. Rapamycin (Sirolimus) purchased from Selleck
Method Histological analysis, immunohistochemistry, Liver triglyceride content analysis, real-time PCR
Cell Lines Male SD rats
Concentrations
Incubation Time 7 d
Results To determine the effect of rapamycin, an mTOR inhibitor, in the OA-induced fatty liver, rats were fed 1% OA and administered rapamycin for seven days. OA-induced lipid accumulation was completely inhibited by the treatment with rapamycin (Fig. A). HE and Oil Red O staining of liver sections clearly confi rmed the results (Fig. B). Immunohistochemistry analyses showed signifi cantly repressed SREBP-1 in the rapamycin-cotreatment liver ( Fig. B ). All the downstream effectors of SREBP-1, such as Lxr-α, Acc, Scd-1 and Fas, were consistently suppressed by rapamycin ( Fig. C ).

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Rating
Source Biochem Pharmacol 2011 82, 216-226. Rapamycin (Sirolimus) purchased from Selleck
Method Western blot
Cell Lines H1299 cells
Concentrations 2 μM
Incubation Time 48 h
Results RAD001 and other mTOR inhibitors decreased the levels of survivin protein, as assessed by Western blot analysis, without affecting the levels of other IAP members. In addition, combined treatment with sorafenib and mTOR inhibitor Rapamycin and RAD001 decreased survivin expression to a greater extent than treatment with either alone.

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Rating
Source Biochim Biophys Acta, 2013, 1833(3):652-62. Rapamycin (Sirolimus) purchased from Selleck
Method Measurement of cytosolic free Ca2+concentration ([Ca2+]c )
Cell Lines Human platelets
Concentrations 500 nM
Incubation Time 30 min
Results Rapamycin administration significantly reduced TG-evoked Ca 2+ -entry by 19. 5 ?9.4 %.

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Rating
Source Dr.Ulrich Bommer of University of Wollongong. Rapamycin (Sirolimus) purchased from Selleck
Method Western blot
Cell Lines
Concentrations
Incubation Time 0-6 h
Results Rapamycin inhibits growth-dependent TCTP induction.

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Rating
Source Dr. Zhang of Tianjin Medical University. Rapamycin (Sirolimus) purchased from Selleck
Method Western Blot
Cell Lines HeLa cells
Concentrations 0/2/20/200 nM
Incubation Time 24 h
Results

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Rating
Source Tuberc Respir Dis, 2013, 75(1):9-17. Rapamycin (Sirolimus) purchased from Selleck
Method Microscope imaging
Cell Lines NCI-H1299 cells
Concentrations 10 uM
Incubation Time 48 h
Results Growth inhibition induced by rapamycin or erlotinib is enhanced by combination treatment with monensin in NCI-H1299 cells.

Product Citations (34)

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