Rapamycin (Sirolimus) Licensed by Pfizer

Catalog No.S1039

Rapamycin (Sirolimus) is a specific mTOR inhibitor with IC50 of ~0.1 nM HEK293 cells.

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Rapamycin (Sirolimus) Chemical Structure

Rapamycin (Sirolimus) Chemical Structure
Molecular Weight: 914.18

Validation & Quality Control

Cited by 62 publications:

12 customer reviews :

Quality Control & MSDS

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Product Information

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  • Research Area
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

Description Rapamycin (Sirolimus) is a specific mTOR inhibitor with IC50 of ~0.1 nM HEK293 cells.
Targets mTOR [1]
(HEK293 cells)
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]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
HT-29M1jwPWN6fG:2b4jpZ{BCe3OjeR?=M{HVRVExKG6PMXe3NkBpNYXjPXE{TE2VTx?=NGq3eZhRd3SnboTpZZRmeyClYX3weI91cGWlaX6tbY5lfWOnZDDjfZRwfG:6aXPpeJk>NG\ZPVEzPDlyMEi3Ny=>
HT-29M{TnVGN6fG:2b4jpZ{BCe3OjeR?=NXP1OmtwOTBibl2=M1K1Z|czKGh?MYPEUXNQMlm0VI91\W62aXH0[ZMh\GmpaYTvfIlvNWmwZIXj[YQh[3m2b4TvfIlkcXS7NHLJSW4zPDlyMEi3Ny=>
HT-29MkW1R5l1d3SxeHnjJGF{e2G7NETYR3IyOCCwTR?=NF\VfIE4OiCqMn\SSG1UVw>?NEPzfWJRd3SnboTpZZRmeyB3LX\seY9zd3W{YXPpcE1qdmS3Y3XkJIN6fG:2b4jpZ4l1gQ>?MUKyOFkxODh5Mx?=
PC3NIjUXFJMcW6jc3WgRZN{[Xl?MnLiNVAxKG6PMkiyNUBpNUPBWnQ{TE2VTx?=NGq1dWdRd3SnboTsfUBqdmirYnn0d{BuXE:ULX3l[IlifGWmIGO2JJBpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhRDFyIH7NMi=>MlPUNlE6Pzh4OEO=
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PC3NEjvU5dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MVmxMlUh|ryPMnHFNUBpM2HQeWROW09?M3P5eWlv\HWlZYOgZY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCSQ{OgZ4VtdHNid3n0bEBKSzVyIH;mJFwyOCCwTR?=NEnFeGMzOTl5OE[4Ny=>
HEK293NXrHemg6TnWwY4Tpc44hSXO|YYm=MojXNVAxKG6PNVHRcI4xQCCqMmO1SG1UVw>?M1XrdmlvcGmkaYTzJHRRSS2rbnT1Z4VlKGSnZ4Lh[IF1cW:wIH;mJHBl[2R2IIfpeIghTUN3MDDv[kA2OCCwTR?=M2jIV|IyPTN7M{Cx
BT-20NIH6Rm1McW6jc3WgRZN{[Xl?NHjXVo0zOCEQvF2=NH;tTpVFVVORMY\Ec4V{KG6xdDDpcohq[mm2IH3UU3JEOiCmZYDlcoRmdnRicFHrWEBUPDd|IIDoc5NxcG:{eXzheIlwdg>?M1TFT|IyOzV|NUWx
U937Moi1RY51cWKjY4TldolidCCDc4PhfS=>NX22O|Q2PTBizszNMYe0PEBpMXLEUXNQMly5TY5lfWOnczDhcpRq[mGldHXybYFtKGGldHn2bZR6KGGpYXnud5Qhf2muZDD0fZBmKEynZ3nvcoVtdGFicH7leY1weGirbHGgVIhqdGGmZXzwbIliNTFiSmKzNkBqdiCXOUO3JINmdGy|Mn3hNlEyPDJzME[=
U937NEj0emxCdnSrYnHjeIVzcWGuIFHzd4F6NXjyTmw6PTBizszNNXrmfIdTPDhiaB?=M3jCOmROW09?M2O2cWRw\XNibn;0JIlv\HWlZTDhcpRq[mGldHXybYFtKGGldHn2bZR6KGGpYXnud5QhVUmSIIDyc5RmcW5vZHXmbYNq\W62IFzl[4lwdmWubHGgdI5mfW2xcHjpcIEhUlJ|Mj2yJIlvKFV7M{egZ4VtdHN?MXeyNVE1OjFyNh?=
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MCF-7M1XBV2F2fG:yaHHnfUBCe3OjeR?=NEf6[40{OCCwTR?=NGrxOG41KGh?MlfISG1UVw>?NGW4WHJKdmS3Y3XzJIF2fG:yaHHnfS=>NYfNcpN6OjByMkixN|Q>
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U87MGMlS1T4lv[XOnIFHzd4F6NHezPJkyKM7:TR?=NHqw[HE3KGh?MXPEUXNQNH7iWmdRd3SnboTsfUBqdmirYnn0d{A1TUKSMTjUO|AqKHCqb4PwbI9zgWyjdHnvci=>NVXNOZU2OTl6NEi0NFQ>
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U87MGMUDLbY5ie2ViQYPzZZk>MUKxJO69VQ>?MWq2JIg>NH7OZodFVVORM2jW[GRw\XNibn;0JIlvcGmkaYSgVE01TUKSMTjUN|cwPDZrIIDoc5NxcG:{eXzheIlwdg>?NFjKNlgyQTh2OESwOC=>
COS7 cells expressing EGFP-HDQ74/rhebNFexenBCfXSxcHjh[5khSXO|YYm=Mlf0NE4zKM7:TR?=NH;6epYzPCCqNH2wZVZFVVORM4LqWGlv\HWlZYOgZZV1d3CqYXf5NUPsd|I2OTh|OUG5OFk>
COS7 cells expressing EGFP-LC3NULCUlhxSXW2b4DoZYd6KEG|c3H5MUSwMlIh|ryPNY\rToM2OjRiaB?=M3;NV2ROW09?MnHNTY5lfWOnczDheZRweGijZ4m=M2\vNlE5OzlzOUS5
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HeLaNH;HOpBHfW6ldHnvckBCe3OjeR?=M3OwcFExOCCwTR?=NX[ydHQ3OzZiaB?=NVXCN4g5TE2VTx?=MlHSTY5lfWOnczDGVmIhUzJyOUXQMEBVOjB7OFysJHczOTBzRjDteZRidnRvdXLpdZVqfGmwQzDpcpRmemGldHnvci=>MYexO|U3OzN6NR?=
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HeLaNH[0RZpHfW6ldHnvckBCe3OjeR?=MV[xNFAhdk1?MmTnN|YhcA>?MmHFSG1UVw>?NHHkNGlKdmS3Y3XzJGZTSi2IS1LQJINwdXCuZYigbY51\XKjY4Tpc44>NI\3bmkyPzV4M{O4OS=>
SYFM3ToZ2Z2dmO2aX;uJGF{e2G7MYWxNFAhdk1?M4T1flI1KGh?MWLEUXNQNGXB[YZKdmS3Y3XzJGZTSi2IS1LQJINwdXCuZYigbY51\XKjY4Tpc44>MVqxO|U3OzN6NR?=
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... Click to View More Cell Line Experimental Data

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.

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

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
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 2016-07-30)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02240407 Not yet recruiting Pompe Disease University of Florida October 2016 Phase 1
NCT02793544 Not yet recruiting Myelodysplastic Syndrome (MDS)|Chronic Lymphocytic Leukemia (CLL)|Chemotherapy-sensitive Lymphoma|Acute Lymphoblastic Leukemia (ALL)/T Lymphoblasti  ...more Myelodysplastic Syndrome (MDS)|Chronic Lymphocytic Leukemia (CLL)|Chemotherapy-sensitive Lymphoma|Acute Lymphoblastic Leukemia (ALL)/T Lymphoblastic Lymphoma|Acute Myelogenous Leukemia (AML)|Acute Biphenotypic Leukemia (ABL)|Acute Undifferentiated Leukemia (AUL) Center for International Blood and Marrow Transplant Rese  ...more Center for International Blood and Marrow Transplant Research|National Marrow Donor Program|Resource for Clinical Investigation in Blood and Marrow Transplantation August 2016 Phase 2
NCT02587325 Not yet recruiting Pulmonary Hypertension Aadi, LLC August 2016 Phase 1
NCT02806947 Not yet recruiting Acute GVHD Medical College of Wisconsin|National Heart, Lung, and Bl  ...more Medical College of Wisconsin|National Heart, Lung, and Blood Institute (NHLBI)|National Cancer Institute (NCI)|Blood and Marrow Transplant Clinical Trials Network|National Marrow Donor Program July 2016 Phase 2
NCT02833506 Not yet recruiting Recurrent Fallopian Tube Carcinoma|Recurrent Ovarian Carcinoma|Recurrent Primary Peritoneal Carcinoma|Stage IIA Fallopian Tube Cancer|Stage IIA Ova  ...more Recurrent Fallopian Tube Carcinoma|Recurrent Ovarian Carcinoma|Recurrent Primary Peritoneal Carcinoma|Stage IIA Fallopian Tube Cancer|Stage IIA Ovarian Cancer|Stage IIB Fallopian Tube Cancer|Stage IIB Ovarian Cancer|Stage IIC Fallopian Tube Cancer|Stage IIC Ovarian Cancer|Stage IIIA Fallopian Tube Cancer|Stage IIIA Ovarian Cancer|Stage IIIA Primary Peritoneal Cancer|Stage IIIB Fallopian Tube Cancer|Stage IIIB Ovarian Cancer|Stage IIIB Primary Peritoneal Cancer|Stage IIIC Fallopian Tube Cancer|Stage IIIC Ovarian Cancer|Stage IIIC Primary Peritoneal Cancer|Stage IV Fallopian Tube Cancer|Stage IV Ovarian Cancer|Stage IV Primary Peritoneal Cancer Roswell Park Cancer Institute|National Cancer Institute (  ...more Roswell Park Cancer Institute|National Cancer Institute (NCI) July 2016 Phase 1

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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 solvent
Synonyms AY 22989,NSC-2260804
Solubility (25°C) * In vitro DMSO 20 mg/mL (21.87 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 2% DMSO+30% PEG 300+5% Tween 80+ddH2O 5mg/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

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

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