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Purity: ≥98%
NVP-BVU972 (also names as BVN972; BVN-972) is a novel c-Met inhibitor with potential anticancer activity. It has an IC50 of 14 nM for c-Met inhibition. Its IC50 values are 82, 66, and 32 nM, respectively, and it demonstrates good anti-proliferative activity against different cancer cells, including EBC-1, GTL-16, and MKN-45.
| Targets |
Met (IC50 = 14 nM)
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| Enzyme Assay |
The assay used to measure enzyme activity is called time resolved fluorescence resonance energy transfer (TR-FRET). This method uses an anti-phospho-tyrosine antibody labeled with Eu as the fluorescence donor and allophycocyanin conjugated to streptavidin as the fluorescence acceptor, which binds to a biotin on the substrate peptide to detect tyrosine phosphorylation. For every variation, the ATP concentration in the kinase reaction is set to Km (4 μM for MET wt, 1 μM for MET Y1230H and MET F1200I), and Km concentrations for ATP are calculated in the absence of NVP-BVU972. In DMSO, NVP-BVU972 is dissolved, diluted, and assayed four times. In white 1536 well plates, kinase reactions are conducted at room temperature using 50 mM Tris-HCl pH 7.5, 8 mM MgCl2, 4 mM MnCl2, 0.05 % Tween 20, 0.05% bovine serum albumin, 0.1 mM EDTA, 1 mM DTT, and 0.1 mM Na3VO4. After incubating NVP-BVU972 and the enzyme in a volume of 2 μL for 20 minutes, 1 μL ATP and 1 μL biotinylated peptide substrate (PTK1) are added to reach final concentrations of Km and 1 μM, respectively. The enzyme concentrations in the reactions are 4 nM for the Y1230H and F1200I variants and 5 nM for MET wt. To reach the final concentrations of 10 mM EDTA, 3.5 nM Eu-labelled antiphospho-tyrosine antibody PY20, and 10 nM streptavidin allophycocyanin, reactions are stopped after 90 minutes by adding 1 μL stop/detection solution. Using an Envision plate reader, time-resolved fluorescence resonance energy transfer is measured (excitation 320 nm, emission 615 nm and 665 nm).
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| Cell Assay |
BaF3 cells with TPR-MET or different mutants of it are cultured in RPMI 1640 medium with 10% fetal calf serum. 10 ng/mL of interleukin-3 (IL-3) is added to the medium in addition for the maintenance of parental BaF3 cells. BaF3 cells are seeded on 96-well plates in triplicates, with 104 cells per well, for proliferation assays. The cells are then incubated with different concentrations of NVP-BVU972 for 72 hours, and the number of viable cells is determined using a resazurin sodium salt dye reduction readout. The XLFit Excel Add-In is used to calculate IC50 values based on a 4-parameter dose response model.
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| References |
| Molecular Formula |
C20H16N6
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| Molecular Weight |
340.38
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| Exact Mass |
340.14
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| Elemental Analysis |
C, 70.57; H, 4.74; N, 24.69
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| CAS # |
1185763-69-2
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| Appearance |
Solid powder
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| SMILES |
CN1C=C(C=N1)C2=NN3C(=NC=C3CC4=CC5=C(C=C4)N=CC=C5)C=C2
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| InChi Key |
RNCNPRCUHHDYPC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H16N6/c1-25-13-16(11-23-25)19-6-7-20-22-12-17(26(20)24-19)10-14-4-5-18-15(9-14)3-2-8-21-18/h2-9,11-13H,10H2,1H3
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| Chemical Name |
6-[[6-(1-methylpyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]methyl]quinoline
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| Synonyms |
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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 |
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| 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: ≥ 2.5 mg/mL (7.34 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 2.5 mg/mL (7.34 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9379 mL | 14.6895 mL | 29.3789 mL | |
| 5 mM | 0.5876 mL | 2.9379 mL | 5.8758 mL | |
| 10 mM | 0.2938 mL | 1.4689 mL | 2.9379 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.
Resistance profile of the MET inhibitor NVP-BVU972. Cancer Res. 2011 Aug 1;71(15):5255-64. |
A, resistance profile of AMG 458.B, model of AMG 458 bound to the MET kinase domain on the basis of the reported crystal structure of MET in complex with a “type II” pyrrolopyridine-pyridone inhibitor of similar chemical structure (PDB code: 3CE3). Cancer Res. 2011 Aug 1;71(15):5255-64. |
Functional characterization of resistance mutations. Cancer Res. 2011 Aug 1;71(15):5255-64. |
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