Rapamycin曾經(jīng)被用作抗真菌抗生素。它通過抑制T細(xì)胞的激活和增殖來發(fā)揮免疫抑制作用。Rapamycin結(jié)合FK結(jié)合蛋白12（FKBP12）形成Rapamycin-FKBP12復(fù)合物，可以抑制mTOR。在HEK293細(xì)胞中，Rapamycin是一種有效而特異性的mTOR抑制劑，其IC50為0.1 nM。Rapamycin結(jié)合FKBP12并特異性地作為mTORC1的變構(gòu)抑制劑。

在所有測試的細(xì)胞系（A549、SPC-A-1、95D和NCI-H446細(xì)胞）中，拉帕霉素（12.5-100 nM；24小時）治療以劑量依賴性方式對肺癌細(xì)胞增殖產(chǎn)生適度的抑制作用，在100 nM時實現(xiàn)約30-40%的細(xì)胞增殖減少，而在12.5 nM時僅有約10%的減少。拉帕霉素不僅能有效地抑制增殖，還能以劑量依賴性方式誘導(dǎo)LEC的凋亡，在HGF管理下通過抑制AKT/mTOR、ERK和JAK2/STAT3信號分子的磷酸化來促進(jìn)LEC的凋亡。

在Ndufs4 - / -小鼠中，雷帕霉素減少了神經(jīng)疾病。在接受雷帕霉素治療的敲除小鼠中，在P35后的每個年齡點上表現(xiàn)出神經(jīng)癥狀的小鼠比例大大降低，并且其中約有一半的小鼠在死亡前從未顯示出明顯的神經(jīng)疾病跡象[2]。單用雷帕霉素具有適度抑制作用。然而，二甲雙胍和雷帕霉素聯(lián)合使用與對照組、單用雷帕霉素組和單用二甲雙胍組相比，能夠顯著增強腫瘤生長的抑制作用[8]。細(xì)胞培養(yǎng)中使用雷帕霉素可顯著抑制c-Myc調(diào)節(jié)基因表達(dá)。在體內(nèi)移植模型下，雷帕霉素通過降低STAT3和c-Myc表達(dá)來抑制肝細(xì)胞癌腫瘤生長[9]。

產(chǎn)品性質(zhì)：

Cas No.：53123-88-9

別名：雷帕霉素; 西羅莫司; Sirolimus; AY-22989

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

分子式;C51H79NO13

分子量:914.18

溶解度:≥ 45.709mg/mL in DMSO, ≥ 58.9 mg/mL in EtOH with ultrasonic

儲存條件:Desiccate at -20°C

注意事項：

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References:

[1]: Tian F, Dong L, 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. doi: 10.3390/ijms150813833. PMID: 25116684; PMCID: PMC4159827.

[2]: Johnson SC, Yanos ME, et,al. mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome. Science. 2013 Dec 20;342(6165):1524-8. doi: 10.1126/science.1244360. Epub 2013 Nov 14. PMID: 24231806; PMCID: PMC4055856.

[3]: Sehgal SN, Baker H, et,al. Rapamycin (AY-22,989), a new antifungal antibiotic. II. Fermentation, isolation and characterization. J Antibiot (Tokyo). 1975 Oct;28(10):727-32. doi: 10.7164/antibiotics.28.727. PMID: 1102509.

[4]: Sehgal SN. Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clin Biochem. 1998 Jul;31(5):335-40. doi: 10.1016/s0009-9120(98)00045-9. PMID: 9721431.

[5]: Edwards SR, Wandless TJ. The rapamycin-binding domain of the protein kinase mammalian target of rapamycin is a destabilizing domain. J Biol Chem. 2007 May 4;282(18):13395-401. doi: 10.1074/jbc.M700498200. Epub 2007 Mar 9. PMID: 17350953; PMCID: PMC3763840.

[6]: Rangaraju S, Verrier JD, et,al. Rapamycin activates autophagy and improves myelination in explant cultures from neuropathic mice. J Neurosci. 2010 Aug 25;30(34):11388-97. doi: 10.1523/JNEUROSCI.1356-10.2010. PMID: 20739560; PMCID: PMC3478092.

[7]: Niu H, Wang J, et,al. Rapamycin potentiates cytotoxicity by docetaxel possibly through downregulation of Survivin in lung cancer cells. J Exp Clin Cancer Res. 2011 Mar 10;30(1):28. doi: 10.1186/1756-9966-30-28. PMID: 21392382; PMCID: PMC3065416.

[8]: Zhang JW, Zhao F, et,al. Metformin synergizes with rapamycin to inhibit the growth of pancreatic cancer in vitro and in vivo. Oncol Lett. 2018 Feb;15(2):1811-1816. doi: 10.3892/ol.2017.7444. Epub 2017 Nov 20. PMID: 29434877; PMCID: PMC5774390.

[9]: Sun L, Yan Y, et,al. Rapamycin targets STAT3 and impacts c-Myc to suppress tumor growth. Cell Chem Biol. 2022 Mar 17;29(3):373-385.e6. doi: 10.1016/j.chembiol.2021.10.006. Epub 2021 Oct 26. PMID: 34706270.