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Rapamycin

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Rapamycin
Sirolimus structure.svg
Sirolimus-from-1C9H-3D-sticks.png
Clinical data
Trade namesRapamune, others
SynonymsRapamycin, ABI-009
License data
Pregnancy
category
  • AU: C
Routes of
administration		By mouth, intravenous, topical
ATC code
Legal status
Legal status
.[4]
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
IUPAC name
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
E number
ECHA InfoCard
Chemical and physical data
FormulaC51H79NO13
Molar mass914.19 g·mol−1
3D model (JSmol)
Solubility in water0.0026 [10]
SMILES
InChI
  (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]

Rapamycin Media

  • A plaque, written in Portuguese, commemorating the discovery of sirolimus on Easter Island, near Rano Kau

  • Figure 4: Proposed mechanism of lysine cyclodeaminase conversion of L-lysine to L-pipecolic acid

References

  1. ↑ Rapamune EPAR. European Medicines Agency (17 September 2018). Retrieved 26 November 2021.
  2. ↑ Rapamune Product information. Union Register of medicinal products (15 March 2001). Retrieved 23 March 2025.
  3. ↑ 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.
  4. ↑ Hyftor Product information. Union Register of medicinal products (26 May 2023). Retrieved 23 March 2025.
  5. ↑ Rapamune- sirolimus solution Rapamune- sirolimus tablet, sugar coated. DailyMed. Retrieved 26 November 2021.
  6. ↑ Fyarro- sirolimus injection, powder, lyophilized, for suspension. DailyMed. Retrieved 19 December 2021.
  7. ↑ Hyftor- sirolimus gel. DailyMed (28 January 2021). Retrieved 23 March 2022.
  8. ↑ Immunosuppression With Sirolimus After Solid Organ Transplantation in Children. Pediatric Pharmacotherapy 12 (2) (2006). Retrieved 4 April 2022.
  9. ↑ Rapamycin. PubChem CompoundNational Center for Biotechnology Information. Retrieved 1 August 2016.
  10. ↑ Solubilization of rapamycin. International Journal of Pharmaceutics 213 (1–2) (February 2001). p. 25–29. doi:10.1016/s0378-5173(00)00617-7.
  11. ↑ MeSH Browser. meshb.nlm.nih.gov. Retrieved 2026-04-01.
  12. ↑ Vézina, Claude. Rapamycin (AY-22,989), a new antifungal antibiotic. J. Antibiot. 28 (10) (1975). p. 721–6. doi:10.7164/antibiotics.28.721.
  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. Extension of chronological life span in yeast by decreased TOR pathway signaling. Genes Dev. 20 (2) (2006). p. 174–84. doi:10.1101/gad.1381406.
  15. ↑ Harrison, David E.. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460 (7253) (2009). p. 392–5. doi:10.1038/nature08221.
  16. ↑ The Times & The Sunday Times (in en). www.thetimes.co.uk. Retrieved 2022-03-26.
  17. ↑ Miller, Richard A.. Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. J. Gerontol. A Biol. Sci. Med. Sci. 66 (2) (2011). p. 191–201. doi:10.1093/gerona/glq178.
  18. ↑ Ingram, Donald K.. Glycolytic inhibition as a strategy for developing calorie restriction mimetics. Experimental Gerontology 46 (2–3) (2011). p. 148–154. doi:10.1016/j.exger.2010.12.001.
  19. ↑ Tardif, Suzette. 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) (2015). p. 577–588. doi:10.1093/gerona/glu101.
  20. ↑ Check Hayden, Erika 2014.. Pet dogs set to test anti-ageing drug. Nature 514 (7524) (2014). p. 546. doi:10.1038/514546a. Retrieved 2 April 2015.
  21. ↑ Amy, Harmon (16 May 2016). "Dogs test drug aimed at humans' biggest killer: age". The New York Times. https://www.nytimes.com/2016/05/17/us/aging-research-disease-dogs.html. Retrieved 18 May 2016. 
  22. ↑ Cota, Daniela. Hypothalamic mTOR signaling regulates food intake. Science 312 (5775) (2006). p. 927–930. doi:10.1126/science.1124147.
  23. ↑ 23.0 23.1 Kriete A. Rule-based cell systems model of aging using feedback loop motifs mediated by stress responses. PLOS Computational Biology 6 (6) (2010). p. e1000820. doi:10.1371/journal.pcbi.1000820.
  24. ↑ Magnuson, Brian. Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks. The Biochemical Journal 441 (1) (2012). p. 1–21. doi:10.1042/BJ20110892.
  25. ↑ 25.0 25.1 Schieke, Stefan M.. The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity. J. Biol. Chem. 281 (37) (2006). p. 27643–27652. doi:10.1074/jbc.M603536200.
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