A8167-S | Rapamycin (Sirolimus) [53123-88-9] Clinisciences

Background

Rapamycin was used as a kind of original antifungal antibiotic, which is produced by Streptomyces hygroscopicus. Now it has been used in the prevention of transplant rejection because of its immunosuppressive effect. It also exhibits activity against several transplantable tumors and slightly activity to inactive against leukemias. The immunosuppressive effect of Rapamycin is exerted by inhibiting the activation and proliferation of T cells. Rapamycin binds to FK-binding protein 12 (FKBP12) and forms the rapamycin-FKBP12 complex, which regulates an enzyme that plays an important role in the progression of the cell cycle.

References:
1. Sehgal, Suren N. "Rapamune®(RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression." Clinical biochemistry 31.5 (1998): 335-340.
2. Sehgal, S. N., H. Baker, and Claude Vézina. "Rapamycin (AY-22,989), a new antifungal antibiotic. II. Fermentation, isolation and characterization." The Journal of antibiotics 28.10 (1975): 727-732.

Product Citation

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Chemical Properties

Physical Appearance	A solid
Storage	Desiccate at -20°C
M.Wt	914.18
Cas No.	53123-88-9
Formula	C₅₁H₇₉NO₁₃
Synonyms	Sirolimus,(-)-Rapamycin, AY-22989, WY-090217, Antibiotic AY22989
Solubility	≥45.7 mg/mL in DMSO; insoluble in H2O; ≥58.9 mg/mL in EtOH with ultrasonic
SDF	Download SDF
Canonical SMILES	O[C@H]1[C@H](OC)C[C@H](C[C@@H](C)[C@H](CC([C@H](C)/C=C(C)/[C@H]([C@@H](OC)C([C@@H](C[C@@H](/C=C/C=C/C=C(C)/[C@@H](OC)C[C@@H]2CC[C@@H](C)[C@@](C(C(N3[C@H]4CCCC3)=O)=O)(O)O2)C)C)=O)O)=O)OC4=O)CC1
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment[1]:
Cell lines	Hepatocyte growth factor (HGF)-induced lens epithelial cells (LECs)
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 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
Reaction Conditions	10 ng/ml, 72h
Applications	Using cell proliferation, cell viability and flow cytometric apoptosis assays, we found that rapamycin potently not only suppressed proliferation but also induced the apoptosis of LECs in a dose-dependent manner under HGF administration. Further investigation of the underlying mechanism using siRNA transfection revealed that rapamycin could promote apoptosis of LECs via inhibiting HGF-induced phosphorylation of AKT/mTOR, ERK and JAK2/STAT3 signaling molecules. Moreover, the forced expression of AKT, ERK and STAT3 could induce a significant suppression of apoptosis in these cells after treatment of rapamycin.
Animal experiment[1]:
Animal models	Ndufs4(−/−) mice
Dosage form	8 mg/kg every other day, intraperitoneal injection
Applications	Rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, robustly enhances survival and attenuates disease progression in a mouse model of Leigh syndrome. Administration of rapamycin to these mice, which are deficient in the mitochondrial respiratory chain subunit Ndufs4 [NADH dehydrogenase (ubiquinone) Fe-S protein 4], delays onset of neurological symptoms, reduces neuroinflammation, and prevents brain lesions. Although the precise mechanism of rescue remains to be determined, rapamycin induces a metabolic shift toward amino acid catabolism and away from glycolysis, alleviating the buildup of glycolytic intermediates. This therapeutic strategy may prove relevant for a broad range of mitochondrial diseases.
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.
References: 1. Tian F, Dong L, Zhou Y et al. Rapamycin-Induced Apoptosis in HGF-Stimulated Lens Epithelial Cells by AKT/mTOR, ERK and JAK2/STAT3 Pathways. Int J Mol Sci. 2014 Aug 11;15(8):13833-48. 2. Johnson SC1, Yanos ME, Kayser EB et al. mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome. Science. 2013 Dec 20;342(6165):1524-8.