NVP-BVU972

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NVP-BVU972 is available in the following compound libraries:

Chemical Library (96-well) Inhibitor Library (96-well) Kinase Inhibitor Library (96-well) Tyrosine Kinase Inhibitor Library (96-Well)

Product Information

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Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

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S2774	MK-2461	<1 mg/mL	99 mg/mL	<1 mg/mL
S1316	AMG-208	<1 mg/mL	0.25 mg/mL	<1 mg/mL
S2859	Golvatinib (E7050)	<1 mg/mL	20 mg/mL	<1 mg/mL
S2747	AMG458	<1 mg/mL	21 mg/mL	<1 mg/mL
S2201	BMS 794833	<1 mg/mL	94 mg/mL	<1 mg/mL
S2761	NVP-BVU972	<1 mg/mL	68 mg/mL	68 mg/mL

Product Description

Biological Activity Protocol Chemical Information Tech Support & FAQs

Biological Activity

Description	NVP-BVU972 is a selective and potent Met inhibitor with IC50 of 14 nM.
Targets	Met
IC50	14 nM ^[1]
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. NVP-BVU972 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. NVP-BVU972 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 NVP-BVU972 screen, Y1230 and D1228 mutations give rise to dramatic shifts in the measured IC50 values for NVP-BVU972 in BaF3 cell line. Resistance triggered by V1155L is more limited to NVP-BVU972. A dose-dependent reduction in TPR-MET phosphorylation when applying NVP-BVU972 to BaF3 cells expressing wild-type TPR-MET. Both Y1230H and D1228A mutations abrogated the effect of NVP-BVU972 but not AMG 458. However, F1200I and L1195V interferes with the potency of NVP-BVU972 to prevent TPR-MET phosphorylation.^[1]
In vivo
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Protocol(Only for Reference)

Kinase Assay: ^[1]

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, K_m concentrations for ATP are determined in the absence of NVP-BVU972, and the ATP concentration in the kinase reaction is set to K_m (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 K_m 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).

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, K_m concentrations for ATP are determined in the absence of NVP-BVU972, and the ATP concentration in the kinase reaction is set to K_m (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 K_m 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).

Cell Assay: ^[1]

Cell lines	BaF3 cells
Concentrations	0.6-9.6 μM
Incubation Time	72 hours
Method	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.

1

References

Chemical Information

Download NVP-BVU972 SDF

Molecular Weight (MW)	340.38
Formula	C₂₀H₁₆N₆
CAS No.	1185763-69-2
Synonyms	N/A

Solubility (25°C) DMSO 68 mg/mL Water <1 mg/mL Ethanol 68 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

Chemical Name	6-((6-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl)methyl)quinoline

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Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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BMS-777607 is a Met-related inhibitor for c-Met, Axl, Ron and Tyro3 with IC50 of 3.9 nM, 1.1 nM, 1.8 nM and 4.3 nM, respectively.
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BMS794833 is a potent ATP competitive inhibitor of Met and VEGFR2 with IC50 of 1.7 nM and 15 nM, respectively.

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Validation & Quality Control

Quality Control & MSDS

Related Compound Libraries

NVP-BVU972 is available in the following compound libraries:

Product Information

Compare c-Met Inhibitors

Research Area

Product Description

Biological Activity

Protocol(Only for Reference)

Kinase Assay: ^[1]

Cell Assay: ^[1]

References

Chemical Information

Research Area

Tech Support & FAQs

If you have any other enquiries, please leave a message.

Related c-Met Inhibitors

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Cat.No.	Product Name	Solubility (25°C)
Cat.No.	Product Name	Water	DMSO	Ethanol
S1068	Crizotinib (PF-02341066)	<1 mg/mL	20 mg/mL	<1 mg/mL
S1119	XL-184 free base (Cabozantinib)	<1 mg/mL	100 mg/mL	<1 mg/mL
S1111	Foretinib (GSK1363089, XL880)	<1 mg/mL	127 mg/mL	<1 mg/mL
S1070	PHA-665752	<1 mg/mL	128 mg/mL	<1 mg/mL
S1080	SU11274	<1 mg/mL	92 mg/mL	2 mg/mL
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S1112	SGX-523	<1 mg/mL	2 mg/mL	<1 mg/mL
S1561	BMS 777607	<1 mg/mL	47 mg/mL	<1 mg/mL
S2753	ARQ 197 (Tivantinib)	<1 mg/mL	74 mg/mL	40 mg/mL
S1114	JNJ-38877605	<1 mg/mL	37 mg/mL	<1 mg/mL
S2788	INCB28060	<1 mg/mL	2 mg/mL	<1 mg/mL
S1361	MGCD-265	<1 mg/mL	104 mg/mL	<1 mg/mL
S2774	MK-2461	<1 mg/mL	99 mg/mL	<1 mg/mL
S1316	AMG-208	<1 mg/mL	0.25 mg/mL	<1 mg/mL
S2859	Golvatinib (E7050)	<1 mg/mL	20 mg/mL	<1 mg/mL
S2747	AMG458	<1 mg/mL	21 mg/mL	<1 mg/mL
S2201	BMS 794833	<1 mg/mL	94 mg/mL	<1 mg/mL
S2761	NVP-BVU972	<1 mg/mL	68 mg/mL	68 mg/mL

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NVP-BVU972

Validation & Quality Control

Quality Control & MSDS

Related Compound Libraries

NVP-BVU972 is available in the following compound libraries:

Product Information

Compare c-Met Inhibitors

Research Area

Product Description

Biological Activity

Protocol(Only for Reference)

Kinase Assay: [1]

Cell Assay: [1]

References

Chemical Information

Research Area

Tech Support & FAQs

If you have any other enquiries, please leave a message.

Related c-Met Inhibitors

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Kinase Assay: ^[1]

Cell Assay: ^[1]