MTOR Inhibitors

The mammalian target of rapamycin (mTOR) is a downstream mediator in the phos-phatidylinositol 3-kinase/Akt signaling pathway which controls translation of proteins that regulate cell growth and proliferation, but also angiogenesis and cell survival.

Temsirolimus

The mTOR is an intracellular component which stimulates protein synthesis by phos-phorylating translation regulators, and contributes to protein degradation and an-giogenesis. Temsirolimus is approved for the treatment advanced renal cell carcinoma. The pharmacokinetics of temsirolimus are best described by a two-compartment mod el, with a terminal half-life of 13 to 25 hours. Elimination is primarily via the feces. Temsirolimus, and its metabolite sirolimus, are substrates of the cytochrome P4503A4/5 isoenzyme system. The primary side effects of temsirolimus include mucositis, diarrhea, maculopapular rash, nausea, leucopenia, thrombocytopenia, and hy-perglycemia.

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