| Name | NVP-BVU972 |
| Description | NVP-BVU972 is a selective and potent Met inhibitor with IC50 of 14 nM. |
| Cell Research | BaF3 cells containing TPR-MET or various mutants thereof are grown in RPMI 1640 medium containing 10% fetal calf serum. For maintenance of parental BaF3 cells the medium is additionally supplemented with 10 ng/mL interleukin-3 (IL-3). For proliferation assays, BaF3 cells are seeded on 96-well-plates in triplicates at 104 cells per well and incubated with various concentrations of NVP-BVU972 for 72 hours followed by quantification of viable cells using a resazurin sodium salt dye reduction readout. IC50 values are determined with the XLFit Excel Add-In using a 4-parameter dose response model.(Only for Reference) |
| Kinase Assay | TR-FRET biochemical assay with MET wild type and mutants: Enzyme activity is measured in a time resolved fluorescence resonance energy transfer (TR-FRET) assay, detecting tyrosine phosphorylation with a Eu-labelled anti-phospho-tyrosine antibody (fluorescence donor) and Allophycocyanin conjugated to Streptavidin (fluorescence acceptor) which binds to a biotin on the substrate peptide. For each variant, Km concentrations for ATP are determined in the absence of NVP-BVU972, and the ATP concentration in the kinase reaction is set to Km (4 μM for MET wt, 1 μM for MET Y1230H and MET F1200I). NVP-BVU972 is dissolved and diluted in DMSO and assayed in quadruplicate. Kinase reactions are carried out in 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, 0.1 mM Na3VO4, in white 1536 well plates at room temperature. NVP-BVU972 and enzyme are incubated in a volume of 2 μL for 20 min, followed by the addition of 1 μL ATP and 1 μL biotinylated peptide substrate (PTK1) to final concentrations of Km and 1 μM, respectively. Enzyme concentrations in the reactions are 5 nM for MET wt, and 4 nM for the F1200I and Y1230H variants. After 90 min, reactions are stopped by addition of 1 μL stop/detection solution to reach final concentrations of 10 mM EDTA, 3.5 nM Eu-labelled antiphospho-tyrosine antibody PY20, and 10 nM Streptavidin Allophycocyanin. Time resolved fluorescence resonance energy transfer is measured in an Envision plate reader (excitation 320 nm, emission 615 nm and 665 nm). |
| In vivo | NVP-BVU972 effectively inhibited the growth of MET gene-dispersed cell lines GTL-16, MKN-45, and EBC-1 with IC50 of 66, 82, and 32 nM, respectively.NVP-BVU972 effectively inhibited the MET kinase, while the inhibition of other kinases (including the most closely related ones), RON, was very low, with an IC50 of >1000 nM.NVP-BVU972 inhibited GTL-16, MKN-45 and EBC-1 with IC50 of >1000 nM.NVP-BVU972 inhibited GTL-16, MKN-45 and EBC-1 with IC50 of >1000 nM. BVU972 inhibited constitutive MET phosphorylation in GTL-16 cells and HGF-stimulated MET phosphorylation in A549 cells with IC50s of 7.3 and 22 nM, respectively.NVP-BVU972 acted on BaF3 cells expressing wild-type TPR-MET and dose-dependently decreased TPR-MET phosphorylation. |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | DMSO : 45 mg/mL (132.21 mM), Sonication is recommended.
Ethanol : 63 mg/mL (185.09 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (5.88 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| Keywords | phosphorylation | NVP-BVU-972 | NVP-BVU972 | NVPBVU972 | NVP-BVU 972 | NVP BVU972 | MET resistance mutations | Met | Inhibitor | inhibit | HGFR | c-Met/HGFR | cMet/HGFR | c-Met | cMet | cancer | BaF3 TPR-MET | BaF3 | anti-proliferation |
| Inhibitors Related | Capmatinib 2HCl | (±)-Norcantharidin | L-Ascorbic acid 2-phosphate trisodium | Crizotinib | Amuvatinib | Norcantharidin | AMG-458 | Cabozantinib S-malate | Capmatinib xHCl | Bacitracin Zinc | Capmatinib | BMS 777607 |
| Related Compound Libraries | Highly Selective Inhibitor Library | Anti-Lung Cancer Compound Library | Target-Focused Phenotypic Screening Library | Anti-Pancreatic Cancer Compound Library | Bioactive Compound Library | Membrane Protein-targeted Compound Library | Tyrosine Kinase Inhibitor Library | Kinase Inhibitor Library | Inhibitor Library | NO PAINS Compound Library | Bioactive Compounds Library Max | Anti-Cancer Compound Library |
United States
