Rapamycin 雷帕霉素；西罗莫司

生物活性

Rapamycin (Sirolimus)是一种选择性的mTOR抑制剂，IC50为~0.1 nM。Rapamycin作用于HEK293细胞，抑制内源性mTOR活性，IC50为~0.1 nM,而iRap和AP21967 作用时，IC50分别为~5 nM 和~10 nM。 Rapamycin处理酿酒酵母，诱导细胞周期停在G1/S期，且抑制翻译。 Rapamycin显著抑制T98G和U87-MG细胞活力，这种作用具有剂量依赖性，IC50分别为2 nM和 1 μM, 而对U373-MG细胞没有作用活性，IC50>25 μM。

使用AbMole产品发表的文献

• Biomed Pharmacother. 2024 Mar;172:116260..

  Panax notoginseng saponins stimulates the differentiation and neurite development of C17.2 neural stem cells against OGD/R injuries via mTOR signaling

• Adv Sci (Weinh). 2023 Mar 27;e2207224.

  Hypoxia Drives Material‐Induced Heterotopic Bone Formation by Enhancing Osteoclastogenesis via M2/Lipid‐Loaded Macrophage Axis

• Metabolism. 2023 Jan 7;140:155398.

  Metformin coordinates with mesenchymal cells to promote VEGF-mediated angiogenesis in diabetic wound healing through Akt/mTOR activation

• Front Immunol. 2023 Mar 14;14:1120996.

  ROS-AMPK/mTOR-dependent enterocyte autophagy is involved in the regulation of Giardia infection-related tight junction protein and nitric oxide levels

• Commun Biol. 2023 Apr 3;6(1):361.

  WSSV exploits AMPK to activate mTORC2 signaling for proliferation by enhancing aerobic glycolysis

• Infect Immun. 2023 Nov 16;91(11):e0010323.

  Effects of Trichinella spiralis and its serine protease inhibitors on autophagy of host small intestinal cells

• J Orthop Surg Res. 2023 Feb 22;18(1):129.

  Osteogenic effects of rapamycin on bone marrow mesenchymal stem cells via inducing autophagy

• Arch Oral Biol. 2023 Apr 18;151:105700.

  Wrinkled topography regulates osteogenesis via autophagy-mediated Wnt/β-catenin signaling pathway in MC3T3-E1 cells

• Mol Cancer. 2022 Mar 18;21(1):77.

  Cholesterol promotes EGFR-TKIs resistance in NSCLC by inducing EGFR/Src/Erk/SP1 signaling-mediated ERRα re-expression

• J Hepatol. 2022 Nov 9;S0168-8278(22)03285-8.

  Hepatocyte-specific Mas activation enhances lipophagy and fatty acid oxidation to protect against acetaminophen-induced hepatotoxicity in mice

• Mol Psychiatry. 2022 Jul 15;1-14.

  Social isolation reinforces aging-related behavioral inflexibility by promoting neuronal necroptosis in basolateral amygdala

• Immunology. 2022 Sep 25.

  mTORC1-GLUT1-mediated glucose metabolism drives hyperactivation of B cells in primary Sjogren's syndrome

• CNS Neurosci Ther. 2022 Nov 24.

  Acupuncture promotes nerve repair through the benign regulation of mTOR-mediated neuronal autophagy in traumatic brain injury rats

• Cell Cycle. 2022 Sep 19;1-23.

  Mechanistic target of rapamycin (mTOR) regulates self-sustained quiescence, tumor indolence and late clinical metastasis in a Beclin-1-dependent manner.

• Exp Cell Res. 2022 Nov 9;422(1):113414.

  Gastric cancer-derived mesenchymal stem cells promote gastric cancer cell lines migration by modulating CD276 expression

• Oxid Med Cell Longev. 2021 Jun 14;2021:6662225.

  Impaired Autophagy Induced by oxLDL/ β 2GPI/anti- β 2GPI Complex through PI3K/AKT/mTOR and eNOS Signaling Pathways Contributes to Endothelial Cell Dysfunction

• Int J Case Rep Orthop. 2021;3(2):129-134.

  Rapamycin's osteogenic effects on bone marrow mesenchymal stem cells through triggering autophagy

• Oncogene. 2020 Apr;39(15):3163-3178.

  The EGFR-ZNF263 Signaling Axis Silences SIX3 in Glioblastoma Epigenetically

• Cell Commun Signal. 2020 Feb 17;18(1):27.

  mTOR May Interact With PARP-1 to Regulate Visible Light-Induced Parthanatos in Photoreceptors

• Mol Immunol. 2020 Jan;117:12-19.

  Toll-like receptor 4 knockout protects against diabetic-induced imbalance of bone metabolism via autophagic suppression.

• Biomed Res Int. 2020 Jun 20;2020:9243681.

  Shenmai Injection Supresses Glycolysis and Enhances Cisplatin Cytotoxicity in Cisplatin-Resistant A549/DDP Cells via the AKT-mTOR-c-Myc Signaling Pathway

• Genes & Diseases. 2020 Jun.

  Metformin ameliorates HMGB1-mediated oxidative stress through mTOR pathway in experimental periodontitis

• Biosci Rep. 2018 Nov 20;38(6).

  Rapamycin attenuates mitochondrial injury and renal tubular cell apoptosis in experimental contrast-induced acute kidney injury in rats.

• BMC Genomics. 2017 Sep 11;18(1):714.

  The dynamic landscape of gene regulation during Bombyx mori oogenesis

• Oncotarget. 2016 Feb 22.

  Mechanosensitive caveolin-1 activation-induced PI3K/Akt/mTOR signaling pathway promotes breast cancer motility, invadopodia formation and metastasis in vivo.

• Mol Med Rep. 2016 Sep;14(3):2194-8.

  Anti‑migratory effect of rapamycin impairs allograft imaging by 18F‑fluorodeoxyglucose‑labeled splenocytes

• APMIS. 2015 Jul;562-70.

  MicroRNA-218 increases cellular sensitivity to Rapamycin via targeting Rictor in cervical cancer.

• 2015 Apr.

  THE MECHANOBIOLOGICAL MECHANISMS OF CAVEOLAE/CAVEOLIN-1 IN LOW SHEAR STRESS-INDUCED BREAST CARCINOMA CELL MIGRATION AND INVASION

产品使用成果展示

	数据来源	BMC Genomics (2017). Additional file 7. Rapamycin (Abmole Bioscience, USA)
	方法	qRT-PCR
	细胞系/动物模型	pupa abdomen
	浓度
	处理时间	48 h
	实验结果	We performed injection experiments involving several inhibitors of the insulin signaling pathway. It was observed that the development of follicles was clearly delayed and the follicles showed abnormalities (Additional file 7), and the expressions of marker genes, like Cyp18a1 and early chorion gene, were up-regulated at choriogenic stages.

	数据来源	Oncotarget (2016). Figure 11. Inhibitors of PI3K (LY294002), Akt (MK-2206), Src (PP2), FAK (PF573228) and mTOR (rapamycin) were purchased from Abmole Bioscience (Houston, TX, USA).
	方法	western blot
	细胞系/动物模型	MDA-MB-231 cells
	浓度	PI3K (10 µM LY294002), Akt (10 µM MK-2206) or mTOR (10 µM rapamycin)
	处理时间	1h
	实验结果	As shown in Figure 11. Pretreating MDA-MB-231 cells with the specific inhibitors of PI3K (10 µM LY294002), Akt (10 µM MK-2206) and mTOR (10 µM rapamycin) completely abolished the LSS-induced MT1-MMP expression, indicating that the PI3K/Akt/mTOR pathway is required for LSS-induced MT1-MMP expression.

	数据来源	Oncotarget (2016). Figure 1. Inhibitors of PI3K (LY294002), Akt (MK-2206), Src (PP2), FAK (PF573228) and mTOR (rapamycin) were purchased from Abmole Bioscience (Houston, TX, USA).
	方法	Cell motility assay
	细胞系/动物模型	MDA-MB-231 cells
	浓度	PI3K (10 μM LY294002), Akt (20 μM MK-2206), mTOR (10 μM rapamycin, Rap), FAK (10 μM PF573228) or Src (10 μM PP2)
	处理时间	1h
	实验结果	"Notably, inhibitors of PI3K (LY294002), Akt (MK-2206) and mTOR (rapamycin) markedly decreased the LSS-induced wound closure activity. However, pretreatment with inhibitors of FAK (PF573228) and Src (PP2) has no effect on the LSS-induced cell motility (Figure 1B). It is suggested that PI3K, Akt and mTOR might be participated LSS-induced cell motility in an FAK and Src-independent manner. "

	数据来源	APMIS (2015). Figure 5.Rapamycin was purchased from Abmole (Shanghai, China)
	方法	mice model bearing cervical cancer
	细胞系/动物模型	C33A cells
	浓度	2.5 mg/kg, intra-peritoneal injection
	处理时间	from the 10th day to 37th day
	实验结果	MicroRNA-218 increased tumor sensitivity to Rapamycin in vivo.Compared to the parental controls, both microRNA-218 overexpression and Rapamycin notably suppressed tumor growth (Fig. 5A, p = 0.023 and p = 0.015, respectively); moreover, the combination of microRNA- 218 overexpression and Rapamycin further enhanced this suppressive effects (Fig. 5A, p < 0.001). In addition, Rapamycin notably suppressed the tumor weights of C33A xenografts (Fig. 5B, p = 0.0019), which was also enhanced by the combined therapy (Fig. 5B, p = 0.0423). As shown in Fig. 5C and D, the single treatment with microRNA-218 or Rapamycin notably downregulated the expression of cyclin D1 (the cell cycle related marker) and upregulated cleaved-caspase-3 (the apoptosis marker).

	数据来源	APMIS (2015). Figure 4.Rapamycin was purchased from Abmole (Shanghai, China)
	方法	Cell cycle analysis
	细胞系/动物模型	C33A cells
	浓度	5nM
	处理时间	24 h
	实验结果	Rapamycin induced G1 phase arrest and upregulated the cell cycle related proteins (cyclin D1 and CDK4) in C33A cells, which was further enhanced by the overexpression of microRNA-218. Consistently, in the other three cervical cancer cell lines, Rapamycin also induced G1 phase arrest and this effect was further enhanced by the overexpression of microRNA-218.

	数据来源	APMIS (2015). Figure 3.Rapamycin was purchased from Abmole (Shanghai, China)
	方法	Apoptosis analysis
	细胞系/动物模型	C33A cells
	浓度	5nM
	处理时间	24 h
	实验结果	Compared to the negative control, Rapamycin induced notable apoptosis and upregulated the apoptosis related proteins like cleaved caspase-3 and cleaved PRAP in C33A cells, which was further enhanced by the overexpression of microRNA-218 (Fig. 3A and B). Consistently, similar effects of microRNA-218 on apoptosis were detected in the other three cervical cell lines (Fig. 3C).

	数据来源	APMIS (2015). Figure 2.Rapamycin was purchased from Abmole (Shanghai, China)
	方法	MTT assay
	细胞系/动物模型	HeLa, SiHa, Caski, and C33A cells
	浓度	0~80nM
	处理时间	72 h
	实验结果	As the MTT assay shown, overexpression of microRNA-218 notably increased cellular sensitivity to Rapamycin in the four cervical cancer cell lines (Fig. 2A–D, IC50 = 31 nM, 27 nM, 19 nM, and 13 nM for the parental HeLa, SiHa, Caski, and C33A cells, IC50 = 8.5 nM, 6.2 nM, 5 nM, and 3.6 nM for HeLa, SiHa, Caski, and C33A cells with microRNA-218 overexpression, p = 0.045, 0.032, 0.018, and 0.009 respectively).

实验参考

体外实验*
细胞系	HeLa, SiHa, Caski, and C33A cells
方法	MTT assay. In brief, 2*103 cells/well were seeded into 96-well plates and routinely cultured overnight. Then, these cells were treated with Rapamycin for 72 h. Next, 5 µL MTT (5 mg/ mL; Sigma-Aldrich) and 200 µL DMSO were sequentially added into each well and the absorbance was measured at the wavelength of 570 nm.
浓度	0~80nM
处理时间	72 h

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

体内实验*
动物模型	cervical cancer C33A cells tumor bearing mice
配制	a solution of 0.2%CMC and 0.25% Tween-80 in ddH2O
剂量	2.5 mg/kg from the 10th day to 37th day
给药处理	intra-peritoneal injection

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

化学性质

分子量	914.18
分子式	C51H79NO13
CAS号	53123-88-9
溶解性（25°C）	DMSO 80 mg/mL
储存条件	粉末型式       -20°C   3年；4°C   2年 溶于溶剂       -80°C   6个月；-20°C   1个月
运输方式	冰袋运输，根据产品的不同，可能会有相应调整。

储备液配制

*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.0939 mL	5.4694 mL	10.9388 mL
5 mM	0.2188 mL	1.0939 mL	2.1878 mL
10 mM	0.1094 mL	0.5469 mL	1.0939 mL

不同实验动物依据体表面积的等效剂量转换表（参考来源于公开文献）

	小鼠	大鼠	兔	豚鼠	仓鼠	狗
重量 (kg)	0.02	0.15	1.8	0.4	0.08	10
体表面积 (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km 系数	3	6	12	8	5	20

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的Km系数
	动物 A的Km系数

例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。

参考文献

[1] Ishikawa T, et al. Intern Med. Retrospective Comparison of Midterm Clinical and Angiographic Outcomes after the Implantation of Paclitaxel- and Sirolimus-Eluting Stents for de novo Coronary Complex Lesions in Nonrandomized Japanese Patients.

[2] Kandula P, et al. Transplantation. Impact of Tacrolimus-Sirolimus Maintenance Immunosuppression on Proteinuria and Kidney Function in Pancreas Transplant Alone Recipients.

[3] Maeng M, et al. BMC Cardiovasc Disord. Comparison of zotarolimus-eluting and sirolimus-eluting coronary stents: a study from the Western Denmark Heart Registry.

[4] Zapata G, et al. Ocul Immunol Inflamm. Topical use of rapamycin in herpetic stromal keratitis.

[5] Thuy L Phung, et al. Cancer Cell. Pathological angiogenesis is induced by sustained Akt signaling and inhibited by rapamycin