PROFILPELAJAR.COM

Rapamycin

Rapamycin
Clinical data
Trade namesRapamune, others
Other namesRapamycin, ABI-009
License data
Pregnancy
category
  • AU: C
Routes of
administration		By mouth, intravenous, topical
ATC code
Legal status
Legal status
.[7]
Pharmacokinetic data
Bioavailability14% (oral solution), lower with high-fat meals; 18% (tablet), higher with high-fat meals[8]
Protein binding92%
MetabolismLiver
Elimination half-life57–63 hours[9]
ExcretionMostly fecal
Identifiers
  • (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-12-[(2R)-1-((1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl)-2-propanyl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.107.147 Edit this at Wikidata
Chemical and physical data
FormulaC51H79NO13
Molar mass914.19 g·mol−1
3D model (JSmol)
Solubility in water0.0026 [10]
  • O[C@@H]1CC[C@H](C[C@H]1OC)C[C@@H](C)[C@@H]4CC(=O)[C@H](C)/C=C(\C)[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(/C)[C@@H](OC)C[C@@H]2CC[C@@H](C)[C@@](O)(O2)C(=O)C(=O)N3CCCC[C@H]3C(=O)O4
  • InChI=1S/C51H79NO13/c1-30-16-12-11-13-17-31(2)42(61-8)28-38-21-19-36(7)51(60,65-38)48(57)49(58)52-23-15-14-18-39(52)50(59)64-43(33(4)26-37-20-22-40(53)44(27-37)62-9)29-41(54)32(3)25-35(6)46(56)47(63-10)45(55)34(5)24-30/h11-13,16-17,25,30,32-34,36-40,42-44,46-47,53,56,60H,14-15,18-24,26-29H2,1-10H3/b13-11+,16-12+,31-17+,35-25+/t30-,32-,33-,34-,36-,37+,38+,39+,40-,42+,43+,44-,46-,47+,51-/m1/s1 checkY
  • Key:QFJCIRLUMZQUOT-HPLJOQBZSA-N checkY
  (verify)

Rapamycin (also known as Rapamune[11] and sirolimus), is a compound produced by the bacterium Streptomyces hygroscopicus.[12]

It is used in medicine to prevent organ transplant rejection.[13] It has immunosuppressant functions in humans and is especially useful in preventing the rejection of kidney transplants. It inhibits activation of T cells and B cells by reducing the production of interleukin-2 (IL-2). Sirolimus is also used as a coating for coronary stents.

Effects on longevity

Rapamycin was first shown to extend lifespan in eukaryotes (actually, yeast cells) in 2006.[14]

In a 2009 study, the lifespans of mice fed rapamycin were increased between 28 and 38% from the beginning of treatment. That is a 9 to 14% increased maximum lifespan. The treatment began in mice aged 20 months, the equivalent of 60 human years.[15][16]

Later, rapamycin has been shown to extend mouse lifespan in several separate experiments.[17][18] It is now being tested for this purpose on nonhuman primates (the marmoset monkey).[19] A study on dogs is also planned.[20][21]

Because rapamycin at high doses can suppress the immune system, people taking rapamycin for transplant or cancer therapy are more susceptible to dangerous infections.[13]

It is thought that some dietary regimes, like restricting calories and methionine, cause lifespan extension by decreasing mTOR activity. It is believed that this is achieved by limiting the essential amino acid leucine, a potent activator of mTOR. The administration of leucine into the rat brain has been shown to decrease food intake and body weight via activation of the mTOR pathway.[22]

According to the free radical theory of aging,[23] reactive oxygen causes damage to mitochondrial proteins, and decreases ATP production. Then, the mTOR pathway is inhibited and ATP consuming protein synthesis is downregulated.[24] This means the proportion of damaged proteins grows. Moreover, disruption of mTORC1 directly inhibits mitochondrial respiration.[25]

These positive feedbacks on the aging process are counteracted by protective mechanisms: decreased mTOR activity (among other factors) upregulates glycolysis,[25] and removal of dysfunctional cellular components by autophagy.[23]

References

  1. ↑ "Rapamune- sirolimus solution Rapamune- sirolimus tablet, sugar coated". DailyMed. Archived from the original on 27 November 2021. Retrieved 26 November 2021.
  2. ↑ "Fyarro- sirolimus injection, powder, lyophilized, for suspension". DailyMed. Archived from the original on 19 December 2021. Retrieved 19 December 2021.
  3. ↑ "Hyftor- sirolimus gel". DailyMed. 28 January 2021. Archived from the original on 24 March 2022. Retrieved 23 March 2022.
  4. ↑ "Rapamune EPAR". European Medicines Agency. 17 September 2018. Archived from the original on 13 August 2021. Retrieved 26 November 2021.
  5. ↑ "Rapamune Product information". Union Register of medicinal products. 15 March 2001. Retrieved 23 March 2025.
  6. ↑ "Hyftor EPAR". European Medicines Agency (EMA). 9 June 2023. Retrieved 12 June 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  7. ↑ "Hyftor Product information". Union Register of medicinal products. 26 May 2023. Retrieved 23 March 2025.
  8. ↑ Buck ML (2006). "Immunosuppression With Sirolimus After Solid Organ Transplantation in Children". Pediatric Pharmacotherapy. 12 (2). Archived from the original on 18 April 2020. Retrieved 4 April 2022.
  9. ↑ "Rapamycin". PubChem Compound. National Center for Biotechnology Information. Archived from the original on 16 August 2016. Retrieved 1 August 2016.
  10. ↑ Simamora P, Alvarez JM, Yalkowsky SH (February 2001). "Solubilization of rapamycin". International Journal of Pharmaceutics. 213 (1–2): 25–29. doi:10.1016/s0378-5173(00)00617-7. PMID 11165091.
  11. ↑ "MeSH Browser". meshb.nlm.nih.gov. Retrieved 2026-04-01.
  12. ↑ Vézina, Claude; Kudelski, Alicia; Sehgal, S. N. (1975). "Rapamycin (AY-22,989), a new antifungal antibiotic". J. Antibiot. 28 (10): 721–6. doi:10.7164/antibiotics.28.721. PMID 1102508.
  13. ↑ 13.0 13.1 "Rapamune Prescribing Information" (PDF). United States Food and Drug Administration. Wyeth Pharmaceuticals, Inc. May 2015. [1]
  14. ↑ Powers, R. Wilson; Kaeberlein, Matt; Caldwell, Seth D.; Kennedy, Brian K.; Fields, Stanley (2006). "Extension of chronological life span in yeast by decreased TOR pathway signaling". Genes Dev. 20 (2): 174–84. doi:10.1101/gad.1381406. PMC 1356109. PMID 16418483.
  15. ↑ Harrison, David E.; Strong, Randy; Sharp, Zelton Dave; Nelson, James F.; Astle, Clinton M.; Flurkey, Kevin; Nadon, Nancy L.; Wilkinson, J. Erby; Frenkel, Krystyna; Carter, Christy S.; Pahor, Marco; Javors, Martin A.; Fernandez, Elizabeth; Miller, Richard A. (2009). "Rapamycin fed late in life extends lifespan in genetically heterogeneous mice". Nature. 460 (7253): 392–5. Bibcode:2009Natur.460..392H. doi:10.1038/nature08221. PMC 2786175. PMID 19587680.
  16. ↑ "The Times & The Sunday Times". www.thetimes.co.uk. Retrieved 2022-03-26.
  17. ↑ Miller, Richard A.; Harrison, David E.; Astle, C. M.; Baur, Joseph A.; Boyd, Angela Rodriguez; De Cabo, Rafael; Fernandez, Elizabeth; Flurkey, Kevin; Javors, Martin A.; Nelson, James F.; Orihuela, Carlos J.; Pletcher, Scott; Sharp, Zelton Dave; Sinclair, David; Starnes, Joseph W.; Wilkinson, J. Erby; Nadon, Nancy L.; Strong, Randy (2011). "Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice". J. Gerontol. A Biol. Sci. Med. Sci. 66 (2): 191–201. doi:10.1093/gerona/glq178. PMC 3021372. PMID 20974732.
  18. ↑ Ingram, Donald K.; Roth, George S. (2011). "Glycolytic inhibition as a strategy for developing calorie restriction mimetics". Experimental Gerontology (review). 46 (2–3): 148–154. doi:10.1016/j.exger.2010.12.001. PMID 21167272. S2CID 5634847.
  19. ↑ Tardif, Suzette; Ross, Corinna; Bergman, Phillip; Fernandez, Elizabeth; Javors, Marty; Salmon, Adam; Spross, Jennifer; Strong, Randy; Richardson, Arlan (2015). "Testing efficacy of administration of the antiaging drug rapamycin in a nonhuman primate, the common marmoset". J Gerontol A Biol Sci Med Sci. 70 (5): 577–588. doi:10.1093/gerona/glu101. PMC 4400395. PMID 25038772.
  20. ↑ Check Hayden, Erika 2014. (2014). "Pet dogs set to test anti-ageing drug". Nature. 514 (7524): 546. Bibcode:2014Natur.514..546C. doi:10.1038/514546a. PMID 25355339. S2CID 4470407. Retrieved 2 April 2015.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  21. ↑ Amy, Harmon (16 May 2016). "Dogs test drug aimed at humans' biggest killer: age". The New York Times. Retrieved 18 May 2016.
  22. ↑ Cota, Daniela; Proulx, Karine; Smith, Kathi A. Blake; Kozma, Sara C.; Thomas, George; Woods, Stephen C.; Seeley, Randy J. (2006). "Hypothalamic mTOR signaling regulates food intake". Science. 312 (5775): 927–930. Bibcode:2006Sci...312..927C. doi:10.1126/science.1124147. PMID 16690869. S2CID 6526786.
  23. ↑ 23.0 23.1 Kriete A; Bosl W.J.; Booker G. (2010). "Rule-based cell systems model of aging using feedback loop motifs mediated by stress responses". PLOS Computational Biology. 6 (6): e1000820. Bibcode:2010PLSCB...6E0820K. doi:10.1371/journal.pcbi.1000820. PMC 2887462. PMID 20585546.{{cite journal}}: CS1 maint: article number as page number (link)
  24. ↑ Magnuson, Brian; Ekim, Bilgen; Fingar, Diane C. (2012). "Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks". The Biochemical Journal. 441 (1): 1–21. doi:10.1042/BJ20110892. ISSN 1470-8728. PMID 22168436.
  25. ↑ 25.0 25.1 Schieke, Stefan M.; Phillips, Darci; McCoy, J. Philip; Aponte, Angel M.; Shen, Rong-Fong; Balaban, Robert S.; Finkel, Toren (2006). "The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity". J. Biol. Chem. 281 (37): 27643–27652. doi:10.1074/jbc.M603536200. PMID 16847060.

Content Disclaimer

Informasi ini disarikan dari Wikipedia dan disajikan kembali untuk tujuan edukasi. Konten tersedia di bawah lisensi CC BY-SA 3.0. Kami tidak bertanggung jawab atas ketidakakuratan data yang bersumber dari kontribusi publik tersebut.

  1. The information displayed on this website is sourced in part or in whole from Wikipedia and has been adapted for the purpose of restating it. We strive to provide accurate and relevant information, however:
  2. There is no guarantee of absolute accuracy. Wikipedia is an open, collaborative project that can be edited by anyone, so information is subject to change.
  3. It is not intended to constitute professional advice. The content displayed is for informational and educational purposes only. For important decisions (e.g., medical, legal, or financial), please consult a professional.
  4. Content copyright. Wikipedia is licensed under the Creative Commons Attribution-ShareAlike License (CC BY-SA). This means that content may be reused with appropriate attribution and shared under a similar license.
  5. Responsible use. Any risk arising from the use of information from this website is entirely the responsibility of the user.