Rapamycin雷帕霉素參數

Rapamycin (Sirolimus) 雷帕霉(mei)素(su)（西(xi)羅mo司）

Rapamycin雷帕霉素定義：

一(yi)種(zhong)新型(xing)大環內酯類(lei)免疫(yi)抑制(zhi)藥物(wu)。通過(guo)與相(xiang)應免疫(yi)嗜素(su)RMBP結(jie)合抑制(zhi)細胞周期G0期和(he)(he)G1期，阻斷G1進入(ru)S期而發揮作用(yong)，其效應為：①抑制(zhi)T和(he)(he)B細胞增殖；②抑制(zhi)IL-1、IL-2、IL-6和(he)(he)IFN-γ誘導的(de)淋巴細胞增殖；③抑制(zhi)IgG和(he)(he)供者特異性抗體(細胞毒(du)抗體)產生；④抑制(zhi)單核細胞增殖。可用(yong)于抗移植排斥反(fan)應和(he)(he)治(zhi)療類(lei)風濕性關節(jie)炎、紅斑狼(lang)瘡等自身免疫(yi)病。

溶解性:可溶解于DMSO (50mg/ml)、甲醇(50 mg/ml)、乙醇、丙酮、等有機溶劑；幾乎不溶于水。

作用

本品抑制由抗原和細(xi)胞(bao)因子（白介(jie)素IL-2、IL-4和IL-15）激發的(de)(de)T淋巴細(xi)胞(bao)的(de)(de)活(huo)化和增殖，它亦抑制抗體的(de)(de)產生(sheng)。在細(xi)胞(bao)中，西(xi)(xi)羅mo司與免疫(yi)嗜素，即FK結合(he)蛋白-12（FKBP-12）結合(he)，生(sheng)成FKBP-12免疫(yi)抑制復(fu)合(he)物(wu)。此復(fu)合(he)物(wu)與哺乳動物(wu)的(de)(de)西(xi)(xi)羅mo司BA分(fen)子（mTOR，一種關鍵的(de)(de)調節激酶(mei)）結合(he)并(bing)抑制其活(huo)性，從而抑制細(xi)胞(bao)周(zhou)期(qi)中G1期(qi)向(xiang)S期(qi)的(de)(de)發展。

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.

儲存條件(jian)：-20℃，避光(guang)防潮密閉干燥。

品名

產地

貨號

規格

單價

備注

特(te)級胎牛(niu)血(xue)清（北美血(xue)源(yuan)）

GIBCO

16000-044

500ml