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Small molecule
PubChem CID 5284616

Sirolimus

Rapamune
Mechanism of action
FKBP-12/mTOR
In plain language
Attaches to a helper protein inside cells and together they switch off mTOR, a signal that tells cells to grow and divide — calming an overactive immune system after a transplant and slowing abnormal cell growth in LAM.
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How it works
Sirolimus is a macrocyclic lactone that inhibits T-lymphocyte activation through a mechanism distinct from calcineurin inhibitors such as cyclosporine and tacrolimus. Sirolimus binds the intracellular immunophilin FKBP-12; the resulting sirolimus-FKBP-12 complex binds and inhibits mTOR (mechanistic target of rapamycin), a serine/threonine that governs cell-cycle progression. By inhibiting mTOR, sirolimus blocks cytokine-driven T-lymphocyte proliferation, arresting the cell cycle at the G1-to-S transition, and also suppresses production.
Therapeutic applications
Per FDA-approved labeling, Rapamune (sirolimus) is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants, typically used initially in combination with cyclosporine and corticosteroids. Sirolimus is also indicated, as a separate approved use, for the treatment of patients with lymphangioleiomyomatosis (LAM).
Class
Therapeutic area
Transplant Immunology
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