In this article, we will discuss Temsirolimus (Mechanism of Action). So, let’s get started.
Mechanism of Action
Temsirolimus is an inhibitor of mTOR (mammalian target of rapamycin). Temsirolimus binds to an intracellular protein (FKBP-12), and the protein-drug complex inhibits the activity of mTOR that controls cell division. Inhibition of mTOR activity resulted in a G1 growth arrest in treated tumor cells. When mTOR was inhibited, its ability to phosphorylate p70S6k and S6 ribosomal protein, which are downstream of mTOR in the PI3 kinase/AKT pathway was blocked. In in vitro studies using renal cell carcinoma cell lines, temsirolimus inhibited the activity of mTOR and resulted in reduced levels of the hypoxia-inducible factors HIF-1 and HIF-2 alpha, and the vascular endothelial growth factor.
Effects on Electrocardiogram: There were no clinically relevant QT changes observed at the recommended dose for Temsirolimus. In a randomized, single-blinded, crossover study, 58 healthy subjects received Temsirolimus 25 mg, placebo, and a single oral dose of moxifloxacin 400 mg. A supratherapeutic Temsirolimus dose was not studied in this randomized QT trial. The largest difference between the upper bound 2-sided 90% CI for the mean difference between Temsirolimus and placebo-corrected QT interval was less than 10 ms. In a different trial in 69 patients with a hematologic malignancy, Temsirolimus doses up to 175 mg were studied. No patient with a normal QTcF at baseline had an increase in QTcF >60 ms. Additionally, there were no patients with a QTcF interval greater than 500 ms.