NVP-BGT226 is a novel orally bioavailable dual PI3K/mTOR inhibitor. It selectively inhibits PI3K and both mTOR complexes mTORC1 and mTORC2, resulting in nearly complete phosphorylation-inhibition of P70S6 and 4E-BP1.

BGT226 demonstrated excellent cellular activities in inhibiting proliferations (IC50: 7-30 nM) of many tested cell lines. Notably, cells that express PIK3CA mutation H1047R are still sensitive to the growth-inhibition of BGT226. Flow cytometric analysis shows accumulation of cells in the G0-G1 phase with concomitant loss in the S-phase. BGT226 induces apoptosis or autophagy of some cancer cells at IC50 less than 25nM. In animal models, BGT226 significantly delays/inhibits tumor growth in a dose-dependent manner. BGT-226 represents a potential candidate for cancer therapy. It has entered phaseI/II clinical trials for treatment of advanced solid tumors (including breast cancer) [1-4].