RESEARCH MONOGRAPH · KDC-MN-095
Rapamycin (Sirolimus)
Rapamycin (sirolimus), sold as Rapamune, is a bacterial natural product originally used as an immunosuppressant after organ transplant. It inhibits the mTOR pathway, a master regulator of cell growth and aging. It is the most studied longevity intervention; Mikhail Blagosklonny's hypothesis that intermittent rapamycin slows aging has driven extensive research. Not stocked by Kodiac. This monograph is provided for research and educational reference.
Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.
mTOR inhibitor / immunosuppressant
A bacterial macrolide isolated from Streptomyces hygroscopicus, FDA-approved as an immunosuppressant and increasingly investigated for longevity applications through mTOR inhibition.
Abstract
Rapamycin (Sirolimus, Rapamune; CAS 53123-88-9; molecular formula C51H79NO13; molecular weight 914.17) is a macrolide compound isolated in 1972 from Streptomyces hygroscopicus from Easter Island (Rapa Nui, providing the name). The compound was approved by the FDA in 1999 as an immunosuppressant for renal transplantation. Mechanism is selective inhibition of mTORC1 (mammalian target of rapamycin complex 1) through binding to FKBP12 and forming a complex that allosterically inhibits mTOR kinase activity. Beyond immunosuppression, rapamycin extends lifespan in multiple model organisms (yeast, worms, flies, mice) when administered late in life, making it the most extensively documented pharmacological intervention for lifespan extension. The Interventions Testing Program (ITP) at NIA showed reproducible lifespan extension in genetically heterogeneous mice. Mechanisms of lifespan extension include reduced cellular senescence, improved autophagy, attenuation of age-related inflammation, and reduced age-related cancer incidence. The compound is increasingly studied for longevity applications in the geroscience literature; intermittent research dosing schedules (reported in the literature around 5 to 10 mg weekly or monthly) are described as a way to reduce immunosuppressive effects. Pharmacokinetics: plasma half-life 60 to 70 hours; high oral bioavailability; CYP3A4 metabolism.
Mechanism of action
Selective mTORC1 inhibitor through FKBP12-rapamycin complex. Reduces senescence, improves autophagy, attenuates age-related inflammation.
Reported research dose ranges
1 to 5 mg (immunosuppression context) and 5 to 10 mg weekly intermittent (longevity research), as reported research dose ranges in the literature.
References
- Harrison DE, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 2009.
- Mannick JB, et al. mTOR inhibition improves immune function in the elderly. Sci Transl Med 2014.
Read the full monograph
The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, reported research dose ranges, sourcing and quality verification, reconstitution and handling, stack interaction considerations, and a curated reference list. Available as a research-use-only PDF download.
The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.
FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.