XL-418

XL-418 is an orally active dual Akt and p70S6K inhibitor with IC₅₀ s of 1 nM for Akt1 and 2 nM for p70S6K. XL-418 inhibits the phosphorylation of ribosomal protein S6 and GSK3β. XL-418 can be used for the study of prostate carcinoma and breast cancer ^[1].

In Vivo, XL-418 (compound 11b; 100 mg/kg; p.o.;twice a day; total five doses) inhibits the phosphorylation of ribosomal protein S6 and GSK3β in the PC-3 prostate carcinoma model^[1]. XL-418 (50 mg/kg; p.o.; once a day; for 15 days) inhibits tumor growth in the PC-3 prostate carcinoma model^[1]. XL-418 (50-100 mg/kg; p.o.; two days every 4 days) shows highly active in this study with 71% tumor growth inhibition for the 50 mg/kg dose and 96% tumor growth inhibition (TGI) for the 100 mg/kg alternate dosing schedule as a single agent^[1].

In Vitro, XL-418 inhibits the phosphorylation of ribosomal protein S6 with IC₅₀ values of 30 nM and 55 nM in A549 and PC-3 cells. XL-418 inhibits the phosphorylation of GSK3β with an IC₅₀ value of 194 nM in PC-3 cells^[1].

References:
[1]. Rice KD, et al. Pyrazolopyrimidines as dual Akt/p70S6K inhibitors. Bioorg Med Chem Lett. 2012 Apr 15;22(8):2693-7.