BGT226 (NVP-BGT226) is a novel class I PI3K/mTOR inhibitor for PI3Kα/β/γ with IC50 of 4 nM/63 nM/38 nM. Phase 1/2.
NVP-BGT226 (BGT226) specifically inhibits p110α, p110β, p110δ, and p110γ, with a preference for the α-isoform (wild type and mutated), and mTOR, with no significant inhibitory activity against other tested kinases. The IC50 of NVP-BGT226 for the individual isoforms of the class I PI3Ks is (±standard deviation) PI3Kα 4 nM (±1), PI3Kβ 63 nM (±10), and PI3Kγ 38 nM (±23) as determined by filter-binding assay. In preclinical studies, NVP-BGT226 inhibits cancer cell proliferation with IC50 values in the low nanomolar range and inhibits solid tumor growth in various mouse xenograft models, including glioblastoma multiforme, breast, and prostate cancer. To evaluate the antiproliferative activity of NVP-BGT226 (BGT226) against head and neck cancer cells, 9 HNSCC cell lines from different sites of the oral cavity and 1 NPC cell line with its cisplatin-resistant variant are used. NVP-BGT226 displays potent growth-inhibitory activity against all tested cell lines, with the IC50 ranging from 7.4 to 30.1 nM. Notably, both Detroit 562 and HONE-1 cells, which express PIK3CA mutation H1047R, are still sensitive to the growth-inhibitory effect of NVP-BGT226 treatment. In addition, the sensitivity to NVP-BGT226 between HONE-1 cells and its cisplatin-resistant variant is almost identical.