| Identification | Back Directory | [Name]
1-(3-(Trifluoromethyl)-4-(piperazin-1-yl)phenyl)-8-(6-methoxypyridin-3-yl)-3-methyl-1H-imidazo[4,5-c]quinolin-2(3H)-one maleic acid salt | [CAS]
1245537-68-1 | [Synonyms]
CS-382
BGT226
NVP-BGT226
BGT-226 maleate
BGT226 (NVP-BGT226)
NVP-BGT226 (BGT226)
NVP-BGT226 (maleate)
NVP-BGT226 USP/EP/BP
NVP-BGT226 (free base)
BGT-226;NVP BGT226 (BGT226)
BGT-226 (Maleic Acid Salt)
BGT226 (NVP-BGT226);NVP-BGT226
BGT226 maleate (NVP-BGT226 maleate)
8-(6-Methoxypyridin-3-yl)-3-methyl-1-(4-(piperazin-1-yl)-3-(trifluoromethyl)phenyl)-1H-imidazo
8-(6-methoxypyridin-3-yl)-3-methyl-1-(4-(piperazin-1-yl)-3-(trifluoromethyl)phenyl)-1H-imidazo[4,5-c]quinolin-2(3H)-one Maleic acid
(Z)-but-2-enedioic acid,8-(6-methoxypyridin-3-yl)-3-methyl-1-[4-piperazin-1-yl-3-(trifluoromethyl)phenyl]imidazo[4,5-c]quinolin-2-one
1-(3-(Trifluoromethyl)-4-(piperazin-1-yl)phenyl)-8-(6-methoxypyridin-3-yl)-3-methyl-1H-imidazo[4,5-c]quinolin-2(3H)-one maleic acid salt | [Molecular Formula]
C28H25F3N6O2.C4H4O4 | [MDL Number]
MFCD22124895 | [MOL File]
1245537-68-1.mol | [Molecular Weight]
650.604 |
| Chemical Properties | Back Directory | [Melting point ]
>215°C (dec.) | [storage temp. ]
Hygroscopic, -20°C Freezer, Under inert atmosphere | [solubility ]
DMSO (Slightly) | [form ]
Solid | [color ]
White to Pale Yellow |
| Hazard Information | Back Directory | [Uses]
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. | [Definition]
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+). | [Enzyme inhibitor]
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. | [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[2]. | Animal Model: | Male athymic mice (strain BALB/cAnN.Cg-Foxn1nu/CrlNarl) with FaDu cell xenografted mouse model[2] | | Dosage: | 2.5 and 5 mg/kg | | Administration: | Oral administration; 21 days | | Result: | Caused 34.7% and 76.1% reduction of the tumor growth. |
| [target]
PI3Kα | [IC 50]
PI3Kα: 4 nM (IC50); PI3Kγ: 38 nM (IC50); PI3Kβ: 63 nM (IC50); mTOR; Autophagy |
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