BGT226 (NVP-BGT226)
Modify Date: 2024-01-02 18:32:53
BGT226 (NVP-BGT226) structure
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Common Name | BGT226 (NVP-BGT226) | ||
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| CAS Number | 1245537-68-1 | Molecular Weight | 650.604 | |
| Density | N/A | Boiling Point | N/A | |
| Molecular Formula | C32H29F3N6O6 | Melting Point | N/A | |
| MSDS | N/A | Flash Point | N/A | |
Use of BGT226 (NVP-BGT226)NVP-BGT226 is a potent pan-class I PI3K and mTOR catalytic inhibitor with IC50s of 4 nM, 63 nM and 38 nM for PI3Kα, PI3Kβ and PI3Kγ. |
| Name | (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 |
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| Synonym | More Synonyms |
| Description | NVP-BGT226 is a potent pan-class I PI3K and mTOR catalytic inhibitor with IC50s of 4 nM, 63 nM and 38 nM for PI3Kα, PI3Kβ and PI3Kγ. |
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| Related Catalog | |
| Target |
PI3Kα:4 nM (IC50) PI3Kγ:38 nM (IC50) PI3Kβ:63 nM (IC50) Autophagy |
| In Vitro | 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[1]. 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[2]. |
| In Vivo | NVP-BGT226 (BGT226) is rapidly absorbed after single-dose oral administration, with median peak plasma concentrations (Cmax) observed between 1.0 and 4.6 h post dose (Tmax). Interpatient variability in Cmax and area under the plasma concentration time curve (AUC0-48) is relatively high and ranged (CV%) from 50% to 100% and from 30% to 200%, respectively, for most cohorts. Systemic exposure to BGT226 increased with increasing dose. It is, however, generally lower than expected based on preclinical data, and this finding is also supported by lower than expected Cmax values, particularly at the 100 mg/day dose. The median terminal elimination half-life ranges from 6 to 9 h after the first dose[1]. Whether oral administration of NVP-BGT226 (BGT226) is effective is determined in vivo. NVP-BGT226 inhibits tumor growth in a dose-dependent manner in a FaDu cell xenografted mouse model. Oral administration of NVP-BGT226 at 2.5 and 5 mg/kg for 3 weeks caused 34.7% and 76.1% reduction of the tumor growth on day 21, respectively (compared with control). NVP-BGT226 causes a diminishment of the cytoplasmic immunoreactivity of p-p70S6K in a dose-dependent manner. Furthermore, results of the electronic microscopic analysis shows the formation of autophagosome as indicated by the formation of double membrane vacuoles and internal debris in mice treated with NVP-BGT226[2]. |
| Cell Assay | Cells in the logarithmic growth phase are cultured at a density of 5,000 to 20,000 cells per milliliter per well in a 24-well plate. The cells are exposed to various concentrations of NVP-BGT226 (BGT226) for 3 generation times. At the end of the incubation period, cells are fixed and stained with 50% ethanol containing 0.5% methylene blue for 30 minutes. The resulting colored residues are dissolved in 1% N-lauroyl-sarcosine, and optical density is read at 550 nm using a microplate reader. The IC50 value resulting from 50% inhibition of cell growth is calculated graphically as a comparison with control groups. Each point represents the average of at least 3 independent experiments run in duplicate[2]. |
| Animal Admin | Mice[2] The antitumor effect of BGT226 is examined in the human FaDu xenografted mice. Subcutaneous inoculation of 5×106 FaDu cells in specific pathogen-free male athymic mice (strain BALB/cAnN.Cg-Foxn1nu/CrlNarl), is applied. The animals are subsequently fed under specific pathogen-free conditions and provided with sterile water and food. When the tumor volume reaches 200 to 400 mm3, animals are assigned to groups randomly and given vehicle, NVP-BGT226 [dissolved in 90% N-methyl-2-pyrrolidone (NMP)/10% PEG300], Rapamycin orally once a day, or LY294002 by intraperitoneal injection 3 times a week. The administrations are scheduled for 21 consecutive days, with tumor size and body weight measured and recorded. At the end of the experiments, animals are euthanized in a CO2-containing chamber, and the tumors are collected and fixed in formaldehyde. |
| References |
| Molecular Formula | C32H29F3N6O6 |
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| Molecular Weight | 650.604 |
| Exact Mass | 650.210083 |
| PSA | 151.81000 |
| LogP | 4.48200 |
| Storage condition | -20℃ |
| UNII-4YG62LG876 |
| BGT226 (NVP-BGT226) |
| BGT226 maleate salt |
| 2H-Imidazo[4,5-c]quinolin-2-one, 1,3-dihydro-8-(6-methoxy-3-pyridinyl)-3-methyl-1-[4-(1-piperazinyl)-3-(trifluoromethyl)phenyl]-, (2Z)-2-butenedioate (1:1) |
| BGT226 |
| 8-(6-Methoxy-3-pyridinyl)-3-methyl-1-[4-(1-piperazinyl)-3-(trifluoromethyl)phenyl]-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one (2Z)-2-butenedioate (1:1) |
| cc-443 |
| NVP-BGT226 |