NVP-BGT226

NVP-BGT226 (BGT226) is a potent, dual PI3K/mTOR inhibitor with a preference for PI3Kα (wild type and mutated) and mTOR (PI3Kα, PI3Kβ and PI3Kγ, IC50=4, 63 and 38 nM) ; displays potent antiproliferative activity against various human head and neck cancer cell lines in vitro (IC50=7.4-30.1 nM), downregulates the expression levels of the downstream proteins p-p70S6K and p-4E-BP1 in cells, induces cell-cycle arrest at the G0-G1 phase at 60 nM; BGT226 significantly delays tumor growth in a dose-dependent manner, along with suppressed cytoplasmic expression of p-p70S6K and the presence of autophagosome formation in xenografted animal modes.Solid Tumors Discontinued (In Vitro) :BGT226 shows significant growth inhibition or signal blockage profiles compared with LY294002 and Rapamycin. BGT226 (10-10000 nM) inhibits FaDu and OECM1 cells growth with IC50s of 23.1±7.4 and 12.5±5.1 nM, respectively .The expression levels of p-mTOR Ser2481 are decreased in BGT226-treated cell lines (200 nM; 24 hours) and both p-AKT Ser473 and p-mTOR Ser2448 are also decreased in BGT226-treated cell lines. (In Vivo) :BGT226 (2.5 and 5 mg/kg; oral administration for 21 days in male athymic mice) causes 34.7% and 76.1% reduction of the tumor growth on day 21 compared with control.