A8167-5mg | Rapamycin (Sirolimus) [53123-88-9] Clinisciences

Background

Rapamycin was used as a kind of original antifungal antibiotic, which is produced by Streptomyces hygroscopicus. Now it has been used in the prevention of transplant rejection because of its immunosuppressive effect. It also exhibits activity against several transplantable tumors and slightly activity to inactive against leukemias. The immunosuppressive effect of Rapamycin is exerted by inhibiting the activation and proliferation of T cells. Rapamycin binds to FK-binding protein 12 (FKBP12) and forms the rapamycin-FKBP12 complex, which regulates an enzyme that plays an important role in the progression of the cell cycle.

References:
1. Sehgal, Suren N. "Rapamune®(RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression." Clinical biochemistry 31.5 (1998): 335-340.
2. Sehgal, S. N., H. Baker, and Claude Vézina. "Rapamycin (AY-22,989), a new antifungal antibiotic. II. Fermentation, isolation and characterization." The Journal of antibiotics 28.10 (1975): 727-732.

Product Citation

1. Weiran Li, Yuhui Yang, et al. "Autophagy mediates cementoblast mineralization through periostin/β-catenin signaling axis under compression." Research Square October 13th, 2022.
2. Yan Tang, David J. Kwiatkowski, et al. "Midkine expression by stem-like tumor cells drives persistence to mTOR inhibition and an immune-suppressive microenvironment." Nat Commun. 2022 Aug 26;13(1):5018. PMID: 36028490
3. Yang Liu, Libo He, et al. "Pharmacological inhibition of sphingolipid synthesis reduces ferroptosis by stimulating the HIF-1 pathway." iScience. 2022 Jun 6;25(7):104533. PMID: 35784791
4. Yogev Sela, Jinyang Li, et al. "Bcl-xL enforces a slow-cycling state necessary for survival in the nutrient-deprived microenvironment of pancreatic cancer." Cancer Res. 2022 May 16;82(10):1890-1908. PMID: 35315913
5. Zheng Zhang, Feng Zhang, et al. "CDC42 controlled apical-basal polarity regulates intestinal stem cell to transit amplifying cell fate transition via YAP-EGF-mTOR signaling." Cell Rep. 2022 Jan 11;38(2):110009. PMID: 35021092
6. Jordan E Hollembeak, Michael A Model. "Stability of Intracellular Protein Concentration under Extreme Osmotic Challenge." Cells. 2021 Dec 14;10(12):3532. PMID: 34944039
7. Jialin He, Jianyang Liu, et al. "OM-MSCs Alleviate the Golgi Apparatus Stress Response following Cerebral Ischemia/Reperfusion Injury via the PEDF-PI3K/Akt/mTOR Signaling Pathway." Oxid Med Cell Longev. 2021 Nov 13;2021:4805040. PMID: 34815829
8. Fang Wang, Jing Zhang, et al. "2-Deoxy-D-glucose impedes T cell-induced apoptosis of keratinocytes in oral lichen planus." J Cell Mol Med. 2021 Nov;25(21):10257-10267. PMID: 34672419
9. Na Li, Ming Yan. "Extracellular IL-37 promotes osteogenic and odontogenic differentiation of human dental pulp stem cells via autophagy." Exp Cell Res. 2021 Oct 1;407(1):112780. PMID: 34411610
10. Yuhui Yang, Yiping Huang, et al. "Compressive force regulates cementoblast migration via downregulation of autophagy." J Periodontol. 2021 Nov;92(11):128-138. PMID: 34231875
11. Xiaoli Liu, Yan Gu, et al. "Honokiol induces paraptosis-like cell death of acute promyelocytic leukemia via mTOR & MAPK signaling pathways activation." Apoptosis. 2021 Apr;26(3-4):195-208. PMID: 33550458
12. Weiwen Wang, Yan Zhang, et al. "CXCR4 induces cell autophagy and maintains EBV latent infection in EBVaGC." Theranostics. 2020 Sep 18;10(25):11549-11561. PMID: 33052232
13. Liu Y, Li J, et al. "Advanced glycation end-products suppress autophagy by AMPK/mTOR signaling pathway to promote vascular calcification." Mol Cell Biochem. 2020;471(1-2):91-100. PMID: 32514882
14. Wang J, Chen Y, et al. "mTORC1-IRE1α pathway activation contributes to palmitate-elicited triglyceride secretion and cell death in hepatocytes." Exp Biol Med (Maywood). 2020;1535370220928276. PMID: 32436749
15. Meng XL, Fu P, et al. "Increased EZH2 Levels in Anterior Cingulate Cortex Microglia Aggravate Neuropathic Pain by Inhibiting Autophagy Following Brachial Plexus Avulsion in Rats." Neurosci Bull. 2020;10.1007/s12264-020-00502-w. PMID: 32346844
16. Xie X, Yang C, et al. "Advanced glycation end products reduce macrophage-mediated killing of Staphylococcus aureus by ARL8 upregulation and inhibition of autolysosome formation." Eur J Immunol. 2020;10.1002/eji.201948477. PMID: 32250445
17. Wang F, Zhang J, et al. "The mTOR-glycolytic pathway promotes T-cell immunobiology in oral lichen planus." Immunobiology. 2020;225(3):151933. PMID: 32201095
18. Zhao F, Wang J, et al. "Neuroprotection by Walnut-derived Peptides through Autophagy Promotion via Akt/mTOR Signaling Pathway against Oxidative Stress in PC12 Cells." J Agric Food Chem. 2020;10.1021/acs.jafc.9b08252. PMID: 32090563
19. Xuyang Zhao, Yadong Ma, et al. "mTORC2 mediate FLCN-induced HIF2α nuclear import and proliferation of clear cell renal cell carcinoma." bioRxiv. 2020 January 13.
20. Mitchell DC, Menon A, et al. "Cyclin-dependent kinase 4 inhibits the translational repressor 4E-BP1 to promote cap-dependent translation during mitosis-G1 transition." FEBS Lett. 2020 Apr;594(8):1307-1318. PMID: 31853978
21. WandaNowaka, Leandro NicolásGrendasa, et al. "Pro-inflammatory monocyte profile in patients with major depressive disorder and suicide behaviour and how ketamine induces anti-inflammatory M2 macrophages by NMDAR and mTOR." EBioMedicine. Available online 18 November 2019.
22. Liu XH, Liang S, et al. "Metabolomics Analysis Identifies Sphingolipids as Key Signaling Moieties in Appressorium Morphogenesis and Function in Magnaporthe oryzae." MBio. 2019 Aug 20;10(4). pii: e01467-19. PMID: 31431550
23. Zhang C, Duan Y, et al. "TFEB mediates immune evasion and resistance to mTOR inhibition of renal cell carcinoma via induction of PD-L1." Clin Cancer Res. 2019 Aug 5. pii: clincanres.0733.2019. PMID: 31383732
24. Li CF, Pan YK, et al. "Autophagy protects HUVECs against ER stress-mediated apoptosis under simulated microgravity." Apoptosis. 2019 Jul 29. PMID: 31359205
25. Ye J, Xue M, et al. "Diosbulbin B-Induced Mitochondria-Dependent Apoptosis in L-02 Hepatocytes is Regulated by Reactive Oxygen Species-Mediated Autophagy." Front Pharmacol. 2019 Jun 19;10:676. PMID: 31275148
26. Wang Z, Zhang Z, et al. "Polysaccharides from Enteromorpha Prolifera Ameliorate Acute Myocardial Infarction in Vitro and in Vivo via Up-Regulating HIF-1α." Int Heart J. 2019 Jun 28. PMID: 31257333
27. Tang RH, Qi RQ, et al. "Interleukin-4 affects microglial autophagic flux." Neural Regen Res. 2019 Sep;14(9):1594-1602. PMID: 31089059
28. Yang D, Zhang B, et al. "COPS5 negatively regulates goat endometrial function via the ERN1 and mTOR-autophagy pathways during early pregnancy." J Cell Physiol. 2019 Aug;234(10):18666-18678. PMID: 30927262
29. Zhang M, Liu F, et al. "The MTOR signaling pathway regulates macrophage differentiation from mouse myeloid progenitors by inhibiting autophagy." Autophagy. 2019 Feb 27:1-13. PMID: 30724690
30. Rossi A, Pakhomova ON, et al. "Mechanisms and immunogenicity of nsPEF-induced cell death in B16F10 melanoma tumors." Sci Rep. 2019 Jan 23;9(1):431. PMID: 30674926
31. Benjamin Cook. "Investigating Autophagy, Extracellular Vesicles, and Glycobiology." Loyola University Chicago.2018.
32. Yang D, Jiang T, et al."CREB3 Regulatory Factor -mTOR-autophagy regulates goat endometrial function during early pregnancy." Biol Reprod. 2018 Feb 13. PMID: 29447354
33. Aluru M, McKinney T, et al. "Mitogen-activated protein kinases, Fus3 and Kss1, regulate chronological lifespan in yeast." Aging (Albany NY). 2017 Dec 21;9(12):2587-2609. PMID: 29273704
34. Yang D, Jiang T, et al. "Hormone regulates endometrial function via cooperation of endoplasmic reticulum stress and mTOR-autophagy." J Cell Physiol. 2017 Dec 5. PMID: 29206294
35. Marsh KM, Schipper D, et al. "Metabolic Impact of Rapamycin (Sirolimus) and B-Estradiol Using Mouse Embryonic Fibroblasts as a Model for Lymphangioleiomyomatosis." Lung. 2017 Jun 2. PMID: 28577037
36. Zhixia Qiu , Shuihong Zhang , et al. "The role of curcumin in disruption of HIF-1α accumulation to alleviate adipose fibrosis via AMPK-mediated mTOR pathway in high-fat diet fed mice." J Funct Foods. 2017 Mar.
37. Li X, Guo K, et al. "5-HT 2 receptor mediates high-fat diet-induced hepatic steatosis and very low density lipoprotein overproduction in rats." Obes Res Clin Pract. 2018 Jan - Feb;12(1S1):16-28. PMID: 27133527
38. Holubova, Kristina, et al. "Rapamycin blocks the antidepressant effect of ketamine in task-dependent manner." Psychopharmacology (2016): 1-21. PMID: 27004790
39. Hagg A, Colgan TD, et al. "Using AAV vectors expressing the β2-adrenoceptor or associated Gα proteins to modulate skeletal muscle mass and muscle fibre size." Sci Rep. 2016 Mar 4;6:23042. PMID: 26972746
40. Fu J, Ma S, et al. "Long-term Stress with Hyperglucocorticoidemia-induced Hepatic Steatosis with VLDL Overproduction Is Dependent on both 5-HT2 Receptor and 5-HT Synthesis in Liver." Int J Biol Sci. 2016 Jan 1;12(2):219-34. PMID: 26884719
41. Ranjan, Kishu, and Chandramani Pathak. "Expression of cFLIPL Determines the Basal Interaction of Bcl‐2 with Beclin‐1 and Regulates p53 Dependent Ubiquitination of Beclin‐1 During Autophagic Stress." Journal of cellular biochemistry (2015). PMID: 26682748
42. Deng, Jiangshan, et al. "Identification of the protective role of DJ-1 in hypoglycemic astrocyte injury using proteomics." Journal of proteome research (2015). PMID: 26057206

Hide ↑↑

Chemical Properties

Physical Appearance	A solid
Storage	Desiccate at -20°C
M.Wt	914.18
Cas No.	53123-88-9
Formula	C₅₁H₇₉NO₁₃
Synonyms	Sirolimus,(-)-Rapamycin, AY-22989, WY-090217, Antibiotic AY22989
Solubility	≥45.7 mg/mL in DMSO; insoluble in H2O; ≥58.9 mg/mL in EtOH with ultrasonic
SDF	Download SDF
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
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment[1]:
Cell lines	Hepatocyte growth factor (HGF)-induced lens epithelial cells (LECs)
Preparation method	The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
Reaction Conditions	10 ng/ml, 72h
Applications	Using cell proliferation, cell viability and flow cytometric apoptosis assays, we found that rapamycin potently not only suppressed proliferation but also induced the apoptosis of LECs in a dose-dependent manner under HGF administration. Further investigation of the underlying mechanism using siRNA transfection revealed that rapamycin could promote apoptosis of LECs via inhibiting HGF-induced phosphorylation of AKT/mTOR, ERK and JAK2/STAT3 signaling molecules. Moreover, the forced expression of AKT, ERK and STAT3 could induce a significant suppression of apoptosis in these cells after treatment of rapamycin.
Animal experiment[1]:
Animal models	Ndufs4(−/−) mice
Dosage form	8 mg/kg every other day, intraperitoneal injection
Applications	Rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, robustly enhances survival and attenuates disease progression in a mouse model of Leigh syndrome. Administration of rapamycin to these mice, which are deficient in the mitochondrial respiratory chain subunit Ndufs4 [NADH dehydrogenase (ubiquinone) Fe-S protein 4], delays onset of neurological symptoms, reduces neuroinflammation, and prevents brain lesions. Although the precise mechanism of rescue remains to be determined, rapamycin induces a metabolic shift toward amino acid catabolism and away from glycolysis, alleviating the buildup of glycolytic intermediates. This therapeutic strategy may prove relevant for a broad range of mitochondrial diseases.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: 1. Tian F, Dong L, Zhou Y 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. 2. Johnson SC1, Yanos ME, Kayser EB et al. mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome. Science. 2013 Dec 20;342(6165):1524-8.