Rapamycin雷帕霉素參數(shù)
Rapamycin (Sirolimus) 雷帕霉素（西羅mo司） 別 名 | 西羅mo司(sirolimus) |
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| Cas 號(hào) | 53123-88-9 | 分子式 | C51H79NO13 | 分子量 | 914.18 | 結(jié)構(gòu)式 |
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Rapamycin雷帕霉素定義： 一種新型大環(huán)內(nèi)酯類(lèi)免疫抑制藥物。通過(guò)與相應(yīng)免疫嗜素RMBP結(jié)合抑制細(xì)胞周期G0期和G1期，阻斷G1進(jìn)入S期而發(fā)揮作用，其效應(yīng)為：①抑制T和B細(xì)胞增殖；②抑制IL-1、IL-2、IL-6和IFN-γ誘導(dǎo)的淋巴細(xì)胞增殖；③抑制IgG和供者特異性抗體(細(xì)胞毒抗體)產(chǎn)生；④抑制單核細(xì)胞增殖?？捎糜诳挂浦才懦夥磻?yīng)和治療類(lèi)風(fēng)濕性關(guān)節(jié)炎、紅斑狼瘡等自身免疫病。 溶解性:可溶解于DMSO (50mg/ml)、甲醇(50 mg/ml)、乙醇、丙酮、等有機(jī)溶劑；幾乎不溶于水。 作用 本品抑制由抗原和細(xì)胞因子（白介素IL-2、IL-4和IL-15）激發(fā)的T淋巴細(xì)胞的活化和增殖，它亦抑制抗體的產(chǎn)生。在細(xì)胞中，西羅mo司與免疫嗜素，即FK結(jié)合蛋白-12（FKBP-12）結(jié)合，生成FKBP-12免疫抑制復(fù)合物。此復(fù)合物與哺乳動(dòng)物的西羅mo司BA分子（mTOR，一種關(guān)鍵的調(diào)節(jié)激酶）結(jié)合并抑制其活性，從而抑制細(xì)胞周期中G1期向S期的發(fā)展。 Trusted Worldwide: 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. 儲(chǔ)存條件：-20℃，避光防潮密閉干燥。
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