Home Protein Tyrosine Kinase c-Met inhibitor - Wnt/beta-catenin inhibitor - Apoptosis related activator Capmatinib For research use only.

Capmatinib

Synonyms: INC280, NVP-INC280, INCB28060

Capmatinib is a novel, ATP-competitive inhibitor of c-MET with IC50 of 0.13 nM in a cell-free assay, inactive against RONβ, as well as EGFR and HER-3. Capmatinib (INCB28060) inhibits Wnt/β-catenin and EMT signaling pathways and induces apoptosis in diffuse gastric cancer positive for c-MET amplification. Phase 1.

Capmatinib Chemical Structure

Capmatinib Chemical Structure

CAS No. 1029712-80-8

Purity & Quality Control

Capmatinib Related Products

Signaling Pathway

c-Met Signaling Pathways

c-Met Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Huh7-SR Cell viability assay 0, 2, 4, 8, 16 h 48 h significantly reduced the viability and strengthened the effects of sorafenib on sorafenib-resistant cells 28164434
HepG2-SR Cell viability assay 0, 2, 4, 8, 16 h 48 h significantly reduced the viability and strengthened the effects of sorafenib on sorafenib-resistant cells 28164434
NCI-H1993 Growth inhibition assay 72 hrs Growth inhibition of human NCI-H1993 cells after 72 hrs by CCK-8 assay, IC50 = 0.0023 μM. 28411455
SNU5 Growth inhibition assay 72 hrs Growth inhibition of human SNU5 cells after 72 hrs by CCK-8 assay, IC50 = 0.0027 μM. 28411455
Click to View More Cell Line Experimental Data

Biological Activity

Description Capmatinib is a novel, ATP-competitive inhibitor of c-MET with IC50 of 0.13 nM in a cell-free assay, inactive against RONβ, as well as EGFR and HER-3. Capmatinib (INCB28060) inhibits Wnt/β-catenin and EMT signaling pathways and induces apoptosis in diffuse gastric cancer positive for c-MET amplification. Phase 1.
Features Inactive against RONβ, another member of the c-MET RTK family, as well as EGFR and HER-3 (members of the EGFR RTK family).
Targets
Wnt/β-catenin [2] c-Met [1]
(Cell-free assay)
0.13 nM
In vitro
In vitro

INCB28060 exhibits picomolar enzymatic potency and is highly specific for c-MET with more than 10,000-fold selectivity over a large panel of human kinases. INCB28060 inhibits human c-MET phosphorylation and c-MET-mediated signaling in cancer cells. INCB28060 inhibits c-MET-dependent cell proliferation and survival, and prevents anchorage-independent cancer cell growth and cell migration. [1]
Kinase Assay c-Met Kinase Assay
The assay buffer contains 50 mM Tris-HCl, 10 mM MgCl2, 100 mM NaCl, 0.1 mg/ml BSA, 5mM DTT, pH 7.8. For HTS 0.8 μL of 5 mM of INCB28060 dissolved in DMSO are dotted on 384-well plates. DMSO titration suggests that the maximum tolerated concentration of the solvent is 4%. To measure IC50s the INCB28060 plate is prepared by 3-fold and 11-point serial dilutions. 0.8 μL of INCB28060 in DMSO is transferred from INCB28060 plate to the assay plate. The final concentration of DMSO is 2%. Solutions of 8 nM unphosphorylated c-Met or 0.5 nM phosphorylated c-Met are prepared in assay buffer. A 1 mM stock solution of peptide substrate Biotin-EQEDEPEGDYFEWLE-amide dissolved in DMSO is diluted to 1 μM in assay buffer containing 400 μM ATP (unphosphorylated c-Met) or 160 uM ATP (phosphorylated c-Met). A 20 μL volume of enzyme solution (or assay buffer for the enzyme blank) is added to the appropriate wells in each plate and then 20 μL/well of substrate solution to initiate the reaction. The plate is protected from light and incubated at 25 °C for 90 minutes. The reaction is stopped by adding 20 μL of a solution containing 45 mM EDTA, 50 mM Tris-HCl, 50 mM NaCl, 0.4 mg/ml BSA, 200 nM SA-APC and 3 nM EUPy20. The plate is incubated for 15-30 minutes at room temperature and HTRF (homogenous time resolved fluorescence) is measured on a Perkin Elmer Fusion α-FP instrument. The HTRF program settings used are as follows: Primary excitation filter 330/30, Primary window: 200 uSec, Primary delay: 50 uSec, Number of flashes: 15, Well read time: 2000
Cell Research Cell lines H441 cells
Concentrations 0.24, 1, 4, 16, 63 nM
Incubation Time 24 hours
Method

H441 cells are seeded in RPMI-1640 medium containing 10% FBS and grown to complete confluence. Gaps are introduced by scraping cells with a P200 pipette tip. Cells are then stimulated with 50 ng/mL recombinant human HGF to induce migration across the gap in the presence of various concentrations of INCB28060. After an overnight incubation, representative photographs are taken and a semiqualitative assessment of inhibition of cell migration is conducted.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-Met / Met 28164434
Immunofluorescence p-EGFR 30390071
Growth inhibition assay Cell viability 28164434
In Vivo
In vivo

INCB28060 shows strong antitumor activity in c-MET-dependent mouse tumor models, even oral treatment of 0.03 mg/kg INCB28060 causes approximately 50% inhibition of c-MET-phosphorylation. Dose-dependent inhibition of tumor growth is observed in tumor-bearing mice. [1]
Animal Research Animal Models Eight-week-old female Balb/c nu/nu mice (Charles River) are inoculated subcutaneously with 4 × 106 tumor cells (S114 model) or with 5 × 106 tumor cells (U-87MG glioblastoma model).
Dosages 3, 10, 30 mg/kg
Administration INCB28060 is orally dosed, twice each day.

Chemical Information & Solubility

Molecular Weight 412.42 Formula

C23H17FN6O
CAS No. 1029712-80-8 SDF Download Capmatinib SDF
Smiles CNC(=O)C1=C(C=C(C=C1)C2=NN3C(=CN=C3N=C2)CC4=CC5=C(C=C4)N=CC=C5)F
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 6 mg/mL ( (14.54 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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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.

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