Sirolimus (formally known as rapamycin) and everolimusblock the activating signal delivered by growth factors, exemplified by the interleukin–2 (IL-2) receptor, by phosphorylation of PHAS-1. After binding to FK-binding protein (FKBP) sirolimus and everolimus interact with the mammalian target of rapamycin (mTOR). PHAS-1 phosphorylation by mTOR is followed by dissociation of the eukaryotic Initiation Factor-4F
Everolimus is approved as an adjunctive agent (in combination with CSA + steroids) for the prevention of acute renal allograft rejection.
Dyslipidemia (increase in total cholesterol and triglycerides) requiring treatment with lipid-lowering drugs is a dose-related side effect of sirolimus therapy.
See also the application of other mTOR inhibitors in the section of Oncology.
I Sirolimus and tacrolimus bind to the same protein, but have different mechanisms of action. II Sirolimus and tacrolimus are both substrates for cytochrome P450 3A4.