1245537-68-1

BGT 226 is a novel phosphatidyl inositol-3 kinase/mammalian target of rapamycin (PI3K/mTOR ) dual inhibitor which has shown to be effective with gefitinib in epidermal growth factor receptor (EGFR) inhibitor-sensitive non-small cell lung cancer (NSCLC) therapy.

ChEBI: BGT226 is the maleate salt of 8-(6-methoxypyridin-3-yl)-3-methyl-1-[4-(piperazin-1-yl)-3-(trifluoromethyl)phenyl]-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one. A dual PI3K/mTOR inhibitor. It has a role as an antineoplastic agent, a mTOR inhibitor and an EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor. It contains a BGT226(1+).

This novel Class I PI3K/mTOR inhibitor (FWfree-base = g/mol; FWmaleate-salt = 650.60 g/mol; CAS 1245537-68-1; Solubility: 30 mg/mL DMSO; <1 mg/mL HO), also known as NVP-BGT226 and 8- (6-methoxypyridin-3-yl) - 2 3-methyl-1- (4- (piperazin-1-yl) -3- (trifluoromethyl) phenyl) -1H-imidazo[4,5- c]quinolin-2 (3H) -one, targets PI3Kα (IC50 = 4 nM), PI3Kβ (IC50 = 63 nM), and PI3Kγ (IC50 = 38 nM). BGT226 is active against all tested cancer cell lines, and cross-resistance is not observed in the cisplatin-resistant cell line . Activation of the AKT/mTOR signal cascade is suppressed by BGT226 in a concentration- and time-dependent manner, with cells accumulating in the G0-G1 phase, attended by concomitant loss in the S-phase. TUNEL assays and analysis of caspase 3/7 and PARP indicate that BGT226 induces cancer cell death through an apoptosis-independent pathway. BGT226 induces autophagy, as indicated by the aggregation and upregulation of the microtubule-associated protein light chain 3B-II, and p62 degradation. Gene silencing of Beclin1 or cotreatment of the autophagosome inhibitor, 3- methyladenine, inhibits the BGT226-induced autophagy and led to the retrieval of colony survival. In a xenografted animal model, BGT226 delays tumor growth in a dose-dependent manner, along with suppressed cytoplasmic expression of p-p70 S6 kinase and the presence of autophagosome formation. BGT226 inhibits growth in common myeloma cell lines and primary myeloma cells at nM-concentrations in a time-dependent and dose-dependent manner. BGT226 also has a potent cytotoxic effect on normoxic and hypoxic hepatocarcinoma cells, inactivating p-Akt and p-S6 at less than 10 nM.

PI3Kα