Ridaforolimus

Ridaforolimus (MK-8669) is a potent and selective mTOR inhibitor; inhibits ribosomal protein S6 phosphorylation with an IC₅₀ of 0.2 nM in HT-1080 cells^[1]. IC50 & Target:IC50: 0.5 nM (HT-1080 cells)^[1] In Vitro: Treatment of HT-1080 fibrosarcoma cells with Ridaforolimus results in a dose-dependent inhibition of phosphorylation of both S6 and 4E-BP1, with IC₅₀s of 0.2 and 5.6 nM, respectively, and EC₅₀s of 0.2 and 1.0 nM, respectively. In HT-1080 cells, the EC₅₀ for inhibition of cell proliferation (0.5 nM) is similar to the EC₅₀s for inhibition of S6 and 4E-BP1 phosphorylation. Exposure to Ridaforolimus reduces the proliferation of cell lines representing a variety of tumor types. Administration of Ridaforolimus to tumor cells in vitro elicit dose-dependent inhibition of mTOR activity with concomitant effects on cell growth and division. Ridaforolimus exhibits a predominantly cytostatic mode of action, consistent with the findings for other mTOR inhibitors. Potent inhibitory effects on vascular endothelial growth factor secretion, endothelial cell growth, and glucose metabolism^[1]. In Vivo: Ridaforolimus inhibits tumor growth in mice bearing PC-3 (prostate), HCT-116 (colon), MCF7 (breast), PANC-1 (pancreas), or A549 (lung) xenografts. Ridaforolimus inhibits tumor growth in a dose-dependent manner, with 0.3 mg/kg being the lowest dose that inhibits tumor growth significantly and 3 and 10 mg/kg doses achieving maximum inhibition^[1].