Sirolimus is a relatively new immunosuppressant drug used to prevent rejection in organ transplantation, and is especially useful in kidney transplants. It is an analogue of rapamycin, a macrolide antibiotic ("-mycin") first discovered in a soil fungus on an island called Rapa Nui.

Despite its similar name, it is not a calcineurin-inhibitor like tacrolimus or cyclosporine but has a similar effect on the immune system as it too prevents production of interleukin-2 (IL-2) by immunocompetent T-lymphocytes. It also has an anti-proliferative effect, similar to mycophenolate mofetil.

The mode of action of sirolimus is that it binds to the cytosolic protein FK-binding protein 12 (FKBP12), in a similar way to tacrolimus. However, unlike the tacrolimus-FKBP12 complex which inhibits calcineurin, the sirolimus-FKBP12 complex binds to the mammalian target of rapamycin (mTOR), which inhibits both IL-2 production and lymphocyte proliferation.

The chief advantage sirolimus over calcineurin-inhibitors is that it is not toxic to kidneys. Transplant patients maintained on calcineurin-inhibitors long-term tend to develop impaired kidney function or even chronic renal failure, and this can be prevented by use of sirolimus instead. It is particularly advantageous in patients with kidney transplants for hemolytic-uremic syndrome as this disease is likely to recur in the transplanted kidney if a calcineurin-inhibitor is used.

Sirolimus can also be used alone or in conjuction with calcineurin-inhibitors and/or mycophenolate mofetil, to provide steroid-free immunosuppression regimes.

The anti-proliferative effect of sirolimus has also been used in the production of sirolimus-eluting stents used to treat obstructed coronary arteries, as it is believed that sirolimus-eluting stents are less likely to cause intimal hyperplasia than ordinary stents. This effect may also be found in other arterial stents.

See also: Everolimus