Home Protein Tyrosine Kinase c-Met inhibitor NVP-BVU972

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NVP-BVU972 c-Met inhibitor

Cat.No.S2761

NVP-BVU972 is a selective and potent Met (c-Met) inhibitor with IC50 of 14 nM.
NVP-BVU972 c-Met inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 340.38

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Quality Control

Batch: S276101 DMSO]68 mg/mL]false]Ethanol]68 mg/mL]false]Water]Insoluble]false Purity: 99.78%
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99.78

Solubility

In vitro
Batch:

DMSO : 68 mg/mL (199.77 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 68 mg/mL

Water : Insoluble

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In vivo
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Chemical Information, Storage & Stability

Molecular Weight 340.38 Formula

C20H16N6

 Storage (From the date of receipt)
CAS No. 1185763-69-2 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles CN1C=C(C=N1)C2=NN3C(=NC=C3CC4=CC5=C(C=C4)N=CC=C5)C=C2

Mechanism of Action

Targets/IC50/Ki
Met
14 nM
In vitro
NVP-BVU972 potently inhibits MET kinase but displays low inhibition against other kinases including the most closely related kinase RON with IC50 values of more than 1000 nM. This compound also suppresses constitutive MET phosphorylation in GTL-16 cells or HGF-stimulated MET phosphorylation in A549 cells with IC50 values of 7.3 nM and 22 nM, respectively. It potently prevents the growth of the MET gene amplified cell lines GTL-16, MKN-45 and EBC-1 with IC50 values of 66 nM, 82 nM and 32 nM, respectively. In line with their high frequency in the this compound screen, Y1230 and D1228 mutations give rise to dramatic shifts in the measured IC50 values for it in BaF3 cell line. Resistance triggered by V1155L is more limited to this chemical. A dose-dependent reduction in TPR-MET phosphorylation when applying it to BaF3 cells expressing wild-type TPR-MET. Both Y1230H and D1228A mutations abrogated the effect of this compound but not AMG 458. However, F1200I and L1195V interferes with the potency of it to prevent TPR-MET phosphorylation.
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 this compound, 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). It 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. This chemical 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).
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