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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Purity: ≥98%
BGT226 (also known as NVP-BGT226) is a novel dual class PI3K(phosphatidylinositol 3-kinase)/mammalian target of rapamycin (mTOR) inhibitor with IC50 of 4 nM/63 nM/38 nM. Cell viability was reduced by about 50% when NVP-BGT226 was used, but this reduction was concentration- but not time-dependent, as compared to untreated control cells. The dual NVP-BGT226 PI3K/mTOR inhibitor induces G0/G1 arrest and functions in part by downregulating Survivin. The IC50 range for NVP-BGT226 was 7.4 to 30.1 nM, and it effectively inhibited the growth activity of cell lines like SCC4, TU183, and KB.
Targets |
PI3Kα (IC50 = 4 nM); PI3Kβ (IC50 = 63 nM); PI3Kγ (IC50 = 38 nM); mTOR; Autophagy
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ln Vitro |
BGT226 shows significant growth inhibition or signal blockage profiles compared with LY294002 and Rapamycin. With IC50 values of 23.1±7.4 and 12.5±5.1, respectively, BGT226 (10–1000 nM) inhibits the growth of FaDu and OECM1 cells[2].
In BGT226-treated cell lines (200 nM; 24 hours), the expression levels of p-mTOR Ser2481 are decreased, and p-AKT Ser473 and p-mTOR Ser2448 are also decreased[2].
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ln Vivo |
BGT226 (2.5 and 5 mg/kg; orally for 21 in male athymic mice) causes 34.7% and 76.1% reduction of the tumor growth on day 21 compared with control[2].
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Enzyme Assay |
BGT226 maleate (NVP-BGT226 maleate) is a PI3K (with IC50s of 4 nM, 63 nM and 38 nM for PI3Kα, PI3Kβ and PI3Kγ) /mTOR dual inhibitor which displays potent growth-inhibitory activity against human head and neck cancer cells.
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Cell Assay |
NCI-H929, U266, RPMI-8226 and OPM2 MM cells are seeded in 96-well plates at a concentration of 1.5 × 104 cells/well in RPMI medium supplemented with 10% fetal bovine serum with or without NVP-BGT226 that is to be tested. Cells are cultured for an additional 12 hours in a humid environment (37 °C/5% CO2) after the addition of BrdU-labelling solution (final concentration: 10 μM) after 36 hours. After a centrifugation of the plates for 10 minutes at 300 g, the supernatants are discarded. For two hours, the plates are dried at 60 °C. After the DNA has been partially digested by nuclease treatment for 30 minutes at 37 °C, it has been fixed with ethanol/HCl for 30 minutes at -20 °C.
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Animal Protocol |
Human FaDu xenografted mice
5 mg/kg for 3 weeks Oral administration |
References |
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Additional Infomation |
BGT226 free base is an imidazoquinoline that is 3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinoline substituted at position 1 by a 3-trifluoromethyl-4-(piperazin-1-yl)phenyl group and at position 8 by a 6-methoxypyridin-3-yl group. 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 is an imidazoquinoline, a N-arylpiperazine, a member of pyridines, an organofluorine compound and an aromatic ether. It is a conjugate base of a BGT226(1+).
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Molecular Formula |
C28H25F3N6O2
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Molecular Weight |
534.53
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Exact Mass |
534.199
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Elemental Analysis |
C, 59.07; H, 4.49; F, 8.76; N, 12.92; O, 14.75
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CAS # |
915020-55-2
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Related CAS # |
BGT226 maleate;1245537-68-1
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PubChem CID |
11978790
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Appearance |
White to off-white solid powder
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Density |
1.4±0.1 g/cm3
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Boiling Point |
713.3±70.0 °C at 760 mmHg
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Flash Point |
385.2±35.7 °C
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Vapour Pressure |
0.0±2.3 mmHg at 25°C
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Index of Refraction |
1.628
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LogP |
3.41
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Hydrogen Bond Donor Count |
1
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Hydrogen Bond Acceptor Count |
9
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Rotatable Bond Count |
4
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Heavy Atom Count |
39
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Complexity |
873
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Defined Atom Stereocenter Count |
0
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SMILES |
FC(C1C([H])=C(C([H])=C([H])C=1N1C([H])([H])C([H])([H])N([H])C([H])([H])C1([H])[H])N1C(N(C([H])([H])[H])C2=C([H])N=C3C([H])=C([H])C(C4=C([H])N=C(C([H])=C4[H])OC([H])([H])[H])=C([H])C3=C12)=O)(F)F
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InChi Key |
BMMXYEBLEBULND-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C28H25F3N6O2/c1-35-24-16-33-22-6-3-17(18-4-8-25(39-2)34-15-18)13-20(22)26(24)37(27(35)38)19-5-7-23(21(14-19)28(29,30)31)36-11-9-32-10-12-36/h3-8,13-16,32H,9-12H2,1-2H3
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Chemical Name |
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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Synonyms |
BGT226; BGT 226; BGT-226; NVP-BGT-226; NVP-BGT 226; NVP-BGT226
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (1.87 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (1.87 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 30% PEG400+0.5% Tween80+5% Propylene glycol : 30mg/mL |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.8708 mL | 9.3540 mL | 18.7080 mL | |
5 mM | 0.3742 mL | 1.8708 mL | 3.7416 mL | |
10 mM | 0.1871 mL | 0.9354 mL | 1.8708 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT00600275 | Completed | Drug: BGT226 | Solid Tumors Breast Cancer Cowden Syndrome |
Novartis Pharmaceuticals | December 2007 | Phase 1 Phase 2 |
Effect of BGT226 on cell cycle. A, cell-cycle distribution of all tested cell lines in the presence of BGT226 or DMSO as control was evaluated by flow cytometric analysis.Clin Cancer Res.2011 Nov 15;17(22):7116-26. td> |
Analysis of autophagy in BGT226-treated cell lines.Clin Cancer Res.2011 Nov 15;17(22):7116-26. td> |
Xenograft model of FaDu cells.Clin Cancer Res.2011 Nov 15;17(22):7116-26. td> |
Analysis of apoptosis in BGT226-treated FaDu cells.Clin Cancer Res.2011 Nov 15;17(22):7116-26. td> |