Rapamycin Basic Info.

 

Synonyms:23,27-epoxy-3h-pyrido(2,1-c)(1,4)oxaazacyclohentriacontine;Nsc-226080;Rapa;Rapamune;Rapamycin;Rapamycin, streptomyces hygroscopicus;Rpm

Cas:53123-88-9

Mf:C51h79no13

Mw:914.18

Einecs:262-640-9

Product categories:Active pharmaceutical ingredients;Immunosuppressant;Pharmaceuticals;Cytokine signaling;Chiral reagents;Heterocycles;Inhibitor;Vivactil;Antibiotic

Chemical properties:White to off-white solid

Assay:99%

 

Rapamycin Application:

 

Sirolimus Rapamycin ,A triene macrolide antibiotic isolated from streptomyces hygroscopicus.Name derived from the native word for easter island, rapa'nui.Used as an immunosuppressant;Antirestenotic.Rapamycin is a triene macrolide discovered in 1995 as a metabolite of streptomyces hygroscopicus found in a soil obtained on rapi nui (easter island).Rapamycin displayed potent and selective antifungal activity, notably against candida albicans.Interest in the metabolite waned until the structural relationship to the potent immunosuppressant fujimycin (antibiotic fk506) was recognised in the mid-1980s.

 

Sirolimus Rapamycin ,This recognition led to the re-discovery of rapamycin as a highly selective antitumour and immunosuppressant.  Rapamycin inhibits the activity of the protein, mtor (mammalian target of rapamycin) which functions in a signalling pathway to promote tumour growth.Rapamycin binds to a receptor protein (fkbp12).The rapamycin/fkb12 complex then binds to mtor and prevents interaction of mtor with target proteins in this signalling pathway.

Packing:Foil bag or as required

 

Working concentration: 

 

- 10-100 nM when used as an inhibitor in the TLR signaling cascade

- 10-500 nM when used to induce autophagy

Purity:>95% (HPLC)

Endotoxin level: <0.125 EU/mg

Solubility: 10 mM in DMSO or 2 mM in ethanol

CAS number: 53123-88-9

Synonym: 23,27-Epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine, Antibiotic AY 22989; NSC 2260804; Sirolimus

Molecular weight: 914.17

Rapamycin is provided as a solid and shipped at room temperature. Store at -20°C. Solid product is stable 1 year at -20°C. Upon resuspension, Rapamycin should be aliquoted and stored at -20°C. Avoid repeated freeze-thaw cycles. Resuspended product is stable for 3 months at -20°C when properly stored.

 

DESCRIPTION

 

Rapamycin is an inhibitor of the Ser/Thr protein kinase named“mammalian target of rapamycin” (mTOR) that regulates cell growth and metabolism in response to environmental cues. Rapamycin is also an inducer of autophagy, as inhibition of mTOR mimics cellular starvation by blocking signals required for cell growth and proliferation1

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Furthermore, mTOR is a downstream target of PI3K, an important actor in TLR signaling2 Indeed, Rapamycin can block TLR2- and TLR4- mediated expression of TNF-a and IL-6 in neutrophils stimulated with Pam3CSK4 or LPS3

 

METHOD

 

Preparation of sterile stock solution (10 mM)

1. Add 550 ml DMSO to 5 mg rapamycin.

2. Vortex until completely solubilized.

3. Prepare aliquots and store at -20 C.

4. Once rapamycin is solubilized, dilutions can be prepared by adding sterile water.

 

Working concentrations:

 

- 10-100 nM when used as an inhibitor in the TLR signaling cascade

- 10-500 nM when used to induce autophagy

 

mTOR inhibition in the TLR signaling cascade:

 

To assess the role of mTOR, the appropriate TLR ligand with or without rapamycin at 10-100 nM was added to HEK-Blue™ hTLR2 or HEK-Blue™ hTLR4 cells, and then incubated at 37 °C. HEK-Blue™ TLR cells are engineered HEK293 cells that stably co-express a human TLR gene and an NF-kB-inducible SEAP (secreted embryonic alkaline phosphatase) reporter gene. To increase the sensitivity to their cognate agonists,HEK-Blue™ TLR2 and HEK-Blue™ TLR4 cells were further transfected with the co-receptors CD14 and MD2/CD14, respectively.

Recognition of a TLR by its cognate receptor triggers a signaling cascade leading to the activation of NF-kB and the production of SEAP. SEAP levels can be determined spectrophotometrically using HEK-Blue™ Detection or QUANTI-Blue™, both are SEAP detection media that turn purple/blue in the presence of alkaline phosphatase.

 

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Lidocaine, along with ethanol, ammonia, and acetic acid, has also been proven to be effective in treating jellyfish stings, both numbing the affected area and preventing further nematocyst discharge.

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