Yes — they are two names for the identical molecule (C51H79NO13, MW 914.17, CAS 53123-88-9). Rapamycin is the discovery name, coined from Rapa Nui (the Polynesian name for Easter Island, where the producing soil sample was collected) plus the antibiotic suffix -mycin; the original laboratory code was AY-22,989. Sirolimus is the International Nonproprietary Name adopted for clinical use, marketed as Rapamune, with newer formulations including Fyarro (albumin-bound, for PEComa) and Hyftor (topical gel for facial angiofibroma). Basic research literature predominantly says rapamycin; clinical and regulatory documents say sirolimus.

Not directly, at least not acutely. The FKBP12–rapamycin complex binds the FRB domain of mTOR, which is accessible in mTORC1 (mTOR–Raptor) but occluded by Rictor in mTORC2. However, Sarbassov et al. (Molecular Cell 2006) showed that prolonged exposure can indirectly suppress mTORC2 in some cell types by sequestering newly synthesized mTOR before complex assembly, with consequent loss of AKT Ser473 phosphorylation. This is an important experimental caveat: for genuinely mTORC2-inclusive inhibition, ATP-competitive mTOR kinase inhibitors such as torin1 or PP242 are used instead.

The strongest evidence is the NIA Interventions Testing Program. Harrison et al. (Nature 2009) reported that rapamycin fed to genetically heterogeneous mice beginning at 600 days of age extended both median and maximal lifespan at three independent test sites — the first drug to extend lifespan when started late in life. Effects have been replicated across dose levels and study designs, extended to other species, and the Dog Aging Project is evaluating companion dogs. In humans, Mannick et al. (Sci Transl Med 2014) showed that low-dose mTOR inhibition improved influenza vaccine responses in elderly subjects. Human lifespan extension remains unproven, and rapamycin is not approved for anti-aging use.

All three are "rapalogs" sharing the same FKBP12-dependent allosteric mTORC1 mechanism. Everolimus is the 40-O-(2-hydroxyethyl) derivative; the added hydroxyethyl group improves solubility and oral bioavailability and shortens the half-life from roughly 60 hours (sirolimus) to about 30 hours, enabling faster dose titration. Temsirolimus is a water-soluble dihydroxymethylpropionic acid ester prodrug that is rapidly converted to sirolimus in vivo, permitting intravenous administration. Because target engagement is essentially identical, selection among them is driven by pharmacokinetics, route and indication.

mTORC1 is the principal negative regulator of autophagy. When nutrients are abundant, active mTORC1 phosphorylates ULK1 at Ser757 to block autophagy initiation and phosphorylates TFEB to keep it cytoplasmic. Rapamycin removes both brakes: ULK1 becomes available for AMPK-dependent activation, and dephosphorylated TFEB enters the nucleus to transcribe the CLEAR network of lysosomal and autophagy genes. Standard readouts include LC3-I→LC3-II conversion, p62/SQSTM1 degradation, and tandem mRFP-GFP-LC3 flux assays, ideally with a bafilomycin A1 or chloroquine clamp to distinguish induction from blocked degradation.

In 1964–65, a Canadian expedition collected soil samples from Easter Island (Rapa Nui). Researchers at Ayerst Research Laboratories isolated a strain of Streptomyces hygroscopicus from one sample, and in 1975 Sehgal, Baker and Vézina described its fermentation product as a new antifungal antibiotic active against Candida albicans, naming it rapamycin after the island. Its potent immunosuppressive activity was recognized subsequently, and it was not until 1994 that Brown et al. and Sabatini et al. independently identified the mammalian target — the protein now known as mTOR.

Sirolimus is very poorly water soluble (0.0026 mg/mL), so aqueous stocks are not feasible. Prepare concentrated stocks in DMSO; ethanol is also usable at roughly 2 mM. For cell assays, typical working concentrations range from low nanomolar (mTORC1 inhibition is achieved at 10–100 nM in most cell lines) to a few hundred nanomolar, diluting the DMSO stock into pre-warmed medium with final DMSO ≤0.1% v/v. For in vivo work, DMSO/PEG400/Tween-80 or microencapsulated chow formulations (as used in the ITP studies) are common. Store the solid at −20°C and aliquot stock solutions to avoid freeze–thaw degradation.

They can, but with an important pharmacological caveat: both bind the same immunophilin, FKBP12. At high concentrations they therefore compete for a shared limited pool, and rapamycin can antagonize FK506-mediated calcineurin inhibition (and vice versa) in vitro — a classic textbook example of competitive interaction at a shared binding protein. Clinically, combined CNI plus mTOR-inhibitor regimens are used but require careful dose reduction, since sirolimus increases calcineurin-inhibitor nephrotoxicity and both are CYP3A4 substrates with substantial pharmacokinetic interaction.

The canonical immunoblot panel is phospho-p70S6K (Thr389), phospho-S6 ribosomal protein (Ser235/236 and Ser240/244), and phospho-4E-BP1 (Thr37/46 and Ser65). p70S6K phosphorylation is highly rapamycin-sensitive and collapses within 30–60 minutes, whereas 4E-BP1 phosphorylation is notoriously rapamycin-resistant at certain sites — a key observation that motivated development of ATP-competitive mTOR kinase inhibitors. For mTORC2 assessment, phospho-AKT (Ser473) should be monitored, which acute rapamycin leaves largely intact.

Every batch ships with a Certificate of Analysis (COA) including HPLC purity, NMR structural confirmation, and MS data. MSDS/SDS, residual solvent data, solubility datasheets, and Certificates of Origin are available on request. Sample evaluation is available for qualified institutions — please contact us for details.