Rapamycin

Biological Activity

Rapamycin (Sirolimus,Rapamune)is an inhibitor of mTOR.The mammalian target of rapamycin (mTOR) is a kinase responsible for mitogen-induced cell proliferation/survival signaling.In vitro, rapamycin inhibited the proliferation of primary bone marrow cells induced by IL-3, GM-CSF, KL, or a complex mixture of factors present in cell-conditioned media.

Product Citations

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

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

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  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
  Rapamycin purchased from AbMole

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

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

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  Commun Biol. 2023 Apr 3;6(1):361.

  WSSV exploits AMPK to activate mTORC2 signaling for proliferation by enhancing aerobic glycolysis
  Rapamycin purchased from AbMole

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

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

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

  Osteogenic effects of rapamycin on bone marrow mesenchymal stem cells via inducing autophagy
  Rapamycin purchased from AbMole

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  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
  Rapamycin purchased from AbMole

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  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.
  Rapamycin purchased from AbMole

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  CNS Neurosci Ther. 2022 Nov 24.

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

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  Immunology. 2022 Sep 25.

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

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  Mol Psychiatry. 2022 Jul 15;1-14.

  Social isolation reinforces aging-related behavioral inflexibility by promoting neuronal necroptosis in basolateral amygdala
  Rapamycin purchased from AbMole

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  Metabolism. 2023 Jan 7;140:155398.

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

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  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
  Rapamycin purchased from AbMole

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  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
  Rapamycin purchased from AbMole

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  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
  Rapamycin purchased from AbMole

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  Genes & Diseases. 2020 Jun.

  Metformin ameliorates HMGB1-mediated oxidative stress through mTOR pathway in experimental periodontitis
  Rapamycin purchased from AbMole

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  Mol Med Rep. 2016 Sep;14(3):2194-8.

  Anti‑migratory effect of rapamycin impairs allograft imaging by 18F‑fluorodeoxyglucose‑labeled splenocytes
  Rapamycin purchased from AbMole

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  2015 Apr.

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

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  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
  Rapamycin purchased from AbMole

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

  The EGFR-ZNF263 Signaling Axis Silences SIX3 in Glioblastoma Epigenetically
  Rapamycin purchased from AbMole

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

  mTOR May Interact With PARP-1 to Regulate Visible Light-Induced Parthanatos in Photoreceptors
  Rapamycin purchased from AbMole

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  Mol Immunol. 2020 Jan;117:12-19.

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

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  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.
  Rapamycin purchased from AbMole

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

  The dynamic landscape of gene regulation during Bombyx mori oogenesis
  Rapamycin purchased from AbMole

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  Oncotarget. 2016 Feb 22.

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

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  APMIS. 2015 Jul;562-70.

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

Customer Product Validations & Biological Datas

	Source	BMC Genomics (2017). Additional file 7. Rapamycin (Abmole Bioscience, USA)
	Method	qRT-PCR
	Cell Lines	pupa abdomen
	Concentrations
	Incubation Time	48 h
	Results	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.

	Source	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).
	Method	western blot
	Cell Lines	MDA-MB-231 cells
	Concentrations	PI3K (10 µM LY294002), Akt (10 µM MK-2206) or mTOR (10 µM rapamycin)
	Incubation Time	1h
	Results	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.

	Source	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).
	Method	Cell motility assay
	Cell Lines	MDA-MB-231 cells
	Concentrations	PI3K (10 μM LY294002), Akt (20 μM MK-2206), mTOR (10 μM rapamycin, Rap), FAK (10 μM PF573228) or Src (10 μM PP2)
	Incubation Time	1h
	Results	"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. "

	Source	APMIS (2015). Figure 5.Rapamycin was purchased from Abmole (Shanghai, China)
	Method	mice model bearing cervical cancer
	Cell Lines	C33A cells
	Concentrations	2.5 mg/kg, intra-peritoneal injection
	Incubation Time	from the 10th day to 37th day
	Results	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).

	Source	APMIS (2015). Figure 4.Rapamycin was purchased from Abmole (Shanghai, China)
	Method	Cell cycle analysis
	Cell Lines	C33A cells
	Concentrations	5nM
	Incubation Time	24 h
	Results	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.

	Source	APMIS (2015). Figure 3.Rapamycin was purchased from Abmole (Shanghai, China)
	Method	Apoptosis analysis
	Cell Lines	C33A cells
	Concentrations	5nM
	Incubation Time	24 h
	Results	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).

	Source	APMIS (2015). Figure 2.Rapamycin was purchased from Abmole (Shanghai, China)
	Method	MTT assay
	Cell Lines	HeLa, SiHa, Caski, and C33A cells
	Concentrations	0~80nM
	Incubation Time	72 h
	Results	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).

Protocol (for reference only)

Cell Experiment
Cell lines	HeLa, SiHa, Caski, and C33A cells
Preparation method	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.
Concentrations	0~80nM
Incubation time	72 h

Animal Experiment
Animal models	cervical cancer C33A cells tumor bearing mice
Formulation	a solution of 0.2%CMC and 0.25% Tween-80 in ddH2O
Dosages	2.5 mg/kg from the 10th day to 37th day
Administration	intra-peritoneal injection

Chemical Information

Molecular Weight	914.18
Formula	C51H79NO13
CAS Number	53123-88-9
Solubility (25°C)	DMSO 80 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[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