1. PI3K/Akt/mTOR
    Autophagy
  2. PI3K
    Autophagy

NVP-BGT226 

Cat. No.: HY-13334 Purity: 99.73%
Data Sheet SDS Handling Instructions

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.

For research use only. We do not sell to patients.
NVP-BGT226 Chemical Structure

NVP-BGT226 Chemical Structure

CAS No. : 1245537-68-1

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 283 In-stock
5 mg USD 198 In-stock
10 mg USD 330 In-stock
50 mg USD 900 In-stock
100 mg USD 1248 In-stock
200 mg   Get quote  
500 mg   Get quote  

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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

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.

IC50 & Target

IC50: 4 nM (PI3Kα), 63 nM (PI3Kβ), 38 nM (PI3Kγ)[1]

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].

References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 1.5370 mL 7.6852 mL 15.3704 mL
5 mM 0.3074 mL 1.5370 mL 3.0741 mL
10 mM 0.1537 mL 0.7685 mL 1.5370 mL
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[2]

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].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

NVP-BGT226 (BGT226) is dissolved in 90% N-methyl-2-pyrrolidone (NMP)/10% PEG300[2].

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.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

650.6

Formula

C₃₂H₂₉F₃N₆O₆

CAS No.

1245537-68-1

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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Product Name:
NVP-BGT226
Cat. No.:
HY-13334
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