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產(chǎn)品名稱： 雷帕霉素 Rapamycin >99%

廠家編號(hào)：R-5000

CAS號(hào)：53123-88-9

規(guī)格和報(bào)價(jià)：50mg/700元 100mg/1000元 1g/6000元

產(chǎn)品描述：

M.W. 914.17 C51H79NO13 [53123-88-9] M.I. 12: 8288 M.I. 14: 8114

Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 200 mg/mL; soluble in ethanol at 50 mg/mL; very poorly soluble in water; maximum solubility in plain water is estimated to be about 5-20 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A

Trusted Worlwide: more than 10,000 vials of our rapamycin have been shipped to more than 2,500 laboratories worldwide since 2002.

Immunosuppressant, related to FK-506, but without calcineurin inhibitory activity even when complexed to FK-506 binding protein. Selectively blocks signaling that leads to p70 S6 kinase activation (IC50 = 50 pM). Terada, N., et al. "Failure of rapamycin to block proliferation once resting cells have entered the cell cycle despite inactivation of p70 S6 kinase." J. Biol. Chem. 268: 12062-12068 (1993). Fingar, D.C., et al. "Dissociation of pp70 ribosomal protein S6 kinase from insulin-stimulated glucose transport in 3T3-L1 adipocytes." J. Biol. Chem. 268: 3005-3008 (1993). Price, D.J., et al. "Rapamycin-induced inhibition of the 70-kilodalton S6 protein kinase." Science 257: 973-977 (1992). Chung, J., et al. "Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases." Cell 69: 1227-1236 (1992).

Lymphokine-induced cell proliferation at the G1 phase is inhibited and apoptosis in a murine B cell line is induced by rapamycin. Rapamycin arrests the Saccharomyces cerevisiae cell cycle irreversibly in the G1 phase. Morice, W.G. ,et al. "Rapamycin-induced inhibition of p34cdc2 kinase activation is associated with G1/S-phase growth arrest in T lymphocytes." J. Biol. Chem. 268: 3734-3738 (1993). Kay, J.E., et al. "Inhibition of T and B lymphocyte proliferation by rapamycin." Immunology 72: 544-549 (1991). Heitman, J., et al. "Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast." Science 253: 905-909 (1991).

Rapamycin extended median and maximal lifespan of both male and female mice when fed late in life. Harrison, D.E., et al. "Rapamycin fed late in life extends lifespan in genetically heterogeneous mice." Nature 460: 392-395 (2009).

Rapamycin has shown activity in slowing cellular and organismal aging. Rapamycin abolished nuclear blebbing, delayed the start of cellular senescence, and improved the degradation of progerin in Hutchinson-Gilford progeria syndrome fibroblast cells. It also reduced the formation of insoluble progerin aggregates and resulted in clearance through autophagic mechanisms in normal fibroblasts. Cao, K., et al. "Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford progeria syndrome cells." Sci. Transl. Med. 3: 89ra58 (2011).

Due to a different mechanism of action than FK506 and other immunosuppressants, rapamycin may prove to be important in organ transplant patient therapy. Fewer side effects than the standard anti-rejection treatments have been observed. Proliferation of activated T cells, but not apoptosis, is blocked by rapamycin. The induction of apoptosis of rejection-causing T cells reduces the tendency towards transplant rejection. Schwarz, C. and Oberbauer, R. "The future role of target of rapamycin inhibitors in renal transplantation." Curr Opin Urol. 12: 109-113 (2002). Wells, A.D. et al. "Requirement for T-cell apoptosis in the induction of peripheral transplantation tolerance." Nat. Med. 5: 1303-1307 (1999). Li, Y., et al. "Blocking both signal 1 and signal 2 of T-cell activation prevents apoptosis of alloreactive T cells and induction of peripheral allograft tolerance." Nat. Med. 5: 1298-1302 (1999).

We have had one lot of Selleck Chemical's rapamycin analyzed by a highly experienced and expert clinical analytical laboratory that specializes in rapamycin analyses. Using liquid chromatography - mass spectrometry, they found a purity of 96.7% (cis plus trans) for a lot of Selleck's rapamycin. In contrast, we have proven our rapamycin to be greater than 99% in purity for every lot, no exceptions.

More on the subject of rapamycin purity: HPLC analysis of rapamycin is somewhat complicated. Rapamycin forms several chromatographically separable species in solution, consisting perhaps of different conformers, tautomers, hydrates and/or isomers, but they are all in equilibrium with the major form, trans-rapamycin. We have shown this by collecting the individual impurity peaks in our rapamycin product and individually re-injecting them into the HPLC. In each case, upon re-injection the collected impurity peak is reduced or absent, and the major peak is again trans-rapamycin, of ~95% purity or higher, thus confirming re-equilibration back to the major trans-isomer of rapamycin.

Because we find that all significant impurities (generally, those above 0.1%) in our product, including the cis-isomer, are in equilibrium with the trans isomer in the solution used for analysis, the actual purity of our product is >99% rapamycin, in all of its equilibrium forms. In contrast, material from other suppliers typically contains impurities that do not equilibrate with trans-rapamycin, and thus are genuine contaminants.

These results also indicate that it is probably not possible to obtain the trans isomer in pure form, because in solution it will quickly re-equilibrate to the mixture of cis and trans.

Rapamycin formulations for in vivo use: Many of our customers have asked for information about preparing formulations of rapamycin for administration to animals. Here are several journal citations and links for information on this topic:

http://circ.ahajournals.org/cgi/content/full/99/16/2164 describes a vehicle for rapamycin injection consisting of a rapamycin suspension in 0.2% carboxymethyl cellulose and 0.25% polysorbate-80. They don't say how the suspension was done; one way is to thoroughly agitate or grind the rapamycin in the vehicle. Another way, probably better and easier, is to dissolve the rapamycin at high concentration in DMSO, dimethylformamide or dimethylacetamide, then dilute into the aqueous vehicle--this should give a very fine suspension if agitation is good during addition of the DMSO solution. Injection was i.m. Gallo, R., et al. "Inhibition of Intimal Thickening After Balloon Angioplasty in Porcine Coronary Arteries by Targeting Regulators of the Cell Cycle." Circulation 99: 2164-2170 (1999).

http://www.pnas.org/cgi/reprint/96/15/8657.pdf describes a similar protocol; these workers dissolved the rapamycin in dimethylacetamide, then added it in 1:24 proportion to a vehicle of (final conc.'s) 10% polyethylene glycol (MW avg. = 400) and 17% polyoxyethylene sorbitan monooleate. Injection was i.p. in mice, total vol. of 100 µl. Rivera, V.M., et al. "Long-term regulated expression of growth hormone in mice after intramuscular gene transfer." Proc. Natl. Acad. Sci. USA 96: 8657-8662 (1999).

http://ajpendo.physiology.org/cgi/content/full/279/5/E1080 used 0.75 mg/kg rapamycin in 5% dimethyl sulfoxide, for injection into pigs via jugular vein catheter. Kimball, S.R., et al. "Feeding stimulates protein synthesis in muscle and liver of neonatal pigs through an mTOR-dependent process." Am. J. Physiol. Endocr. metab. 279: E1080-E1087 (2000).

http://www.bloodjournal.org/cgi/content/full/100/3/1084 injected rapamycin in 51% wt/vol polyethylene glycol 300 (PEG300), 2.5% wt/vol polysorbate 80, 10% vol/vol ethanol, i.p. Hackstein, H., et al. "Rapamycin inhibits macropinocytosis and mannose receptor-mediated endocytosis by bone marrow-derived dendritic cells." Blood 100: 1084-1087 (2002).

http://cancerres.aacrjournals.org/cgi/content/full/62/24/7291 injected rapamycin i.p. in mice by diluting an ethanol stock solution of rapamycin first into sterile 10% PEG400/8% ethanol and then that solution was further diluted into an equal volume of sterile 10% Tween 80 for a final concentration of 20 µg rapamycin/100 µl. (Most of this information is in the Materials and Methods section of the paper, but the "ethanol stock solution" is mentioned under the Cell Culture and Antibodies section, and the additional details are found in the Regrowth Delay Assay section.) Eshleman, J.S., et al. "Inhibition of the Mammalian Target of Rapamycin Sensitizes U87 Xenografts to Fractionated Radiation Therapy" Cancer Res. 62: 7291-7297 (2002).

The solubility of rapamycin in 50/50 DMSO/water, as used in osmotic pumps, is about 0.5 mg/mL at ambient temperature.

Quantitation of rapamycin, metabolites and related compounds such as everolimus and FK-506 in blood, tissues and other matrices is offered as a service by Rocky Mountain Labs. This firm is not affiliated with LC Labs.

Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use.