temsirolimus

Temsirolimus is an intravenous immunosuppressant and anticancer agent in the rapalog class. It is a prodrug of sirolimus (rapamycin) that is converted to its active form in vivo. Temsirolimus inhibits the mammalian target of rapamycin complex 1 (mTORC1), reducing cell growth and proliferation.

Clinical use: Temsirolimus is approved for the treatment of advanced renal cell carcinoma in adult patients with poor prognosis. It is administered by intravenous infusion, typically as a weekly dose. It has been evaluated in combination with interferon-α, but monotherapy is the standard indication.

Mechanism: Temsirolimus binds to FKBP12 to form a complex that inhibits mTORC1 signaling. This decreases phosphorylation of downstream targets such as p70S6 kinase and 4E-BP1, leading to cell-cycle arrest in G1 and reduced tumor angiogenesis and protein synthesis.

Pharmacology and safety: Temsirolimus is mainly metabolized by CYP3A4 and can interact with strong inhibitors or inducers of this enzyme, altering exposure. Common adverse effects include fatigue, mucositis, rash, edema, hyperglycemia, hyperlipidemia, anemia, thrombocytopenia, and leukopenia. Serious adverse events include noninfectious pneumonitis, hepatic injury, infection, and wound-healing impairment. It is teratogenic and contraindicated in pregnancy.

History and naming: Temsirolimus was developed by Wyeth and received FDA approval in 2009 for advanced RCC. It is marketed under the brand name Torisel.