Are sirolimus and everolimus the same drug?
No – closely related, but not the same molecule. Sirolimus is rapamycin (same drug, two names). Everolimus (brand names include Afinitor and Zortress) is a semi-synthetic derivative of sirolimus – a "rapalog" – with one chemical modification (a 2-hydroxyethyl group at position 40) that gives it better oral bioavailability and a shorter half-life, making it easier to dose predictably for cancer treatment. Both share the same core mechanism: binding FKBP12 and allosterically inhibiting mTORC1.
Same target, same core mechanism
Everolimus works the same way sirolimus does – it's why the Atlas's systematic review of aging-relevant mTOR-inhibitor trials covers both together as one drug class.
- LEE2024 S – the Atlas's systematic review of "rapamycin/rapalogs" in humans explicitly groups sirolimus and its analogs, including everolimus, as one mechanistic class for the purposes of assessing aging-relevant effects.
Where everolimus has its own, separate evidence base
Despite the shared mechanism, everolimus is the rapalog most tested in oncology trials – it has 21 studies in the Atlas, 15 of them human studies or syntheses of human data, most of them in cancer and tuberous sclerosis.
- BAS2012 H – a phase 3 RCT (n=724) showing everolimus added to endocrine therapy roughly doubles progression-free survival in hormone-resistant advanced breast cancer.
- YAO2011 H – a phase 3 RCT (n=410) that made everolimus a standard treatment for pancreatic neuroendocrine tumors, more than doubling progression-free survival (11.0 vs 4.6 months).
- FRA2013 H – a phase 3 RCT (n=117) in tuberous sclerosis showing everolimus shrinks SEGA brain tumors by ≥50% in over a third of patients – a genetic disease where mTORC1 is held on regardless of hormones, though nutrients still gate it.
The practical difference
The two drugs aren't interchangeable in clinical practice, even though they share a mechanism: sirolimus is mainly used for transplant immunosuppression (its original, longest-standing indication), is also approved for lymphangioleiomyomatosis and, as nab-sirolimus, for advanced malignant PEComa, and is the molecule most of the aging/longevity mouse and human trials in this Atlas actually test. Everolimus is mainly used in oncology and for tuberous sclerosis complex (and, as Zortress, in transplantation), where its more predictable pharmacokinetics matter for precise dosing against tumors.
Related entities
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