Capmatinib

Catalog No.S2788 Batch:S278804

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Technical Data

Formula

C23H17FN6O

Molecular Weight 412.42 CAS No. 1029712-80-8
Solubility (25°C)* In vitro DMSO 1.87 mg/mL (4.53 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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.
Targets
Wnt/β-catenin [2] c-Met [1]
(Cell-free assay)
0.13 nM
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]

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]

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).

Protocol (from reference)

Kinase Assay:

[1]

  • 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 Assay:

[1]

  • 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.

Animal Study:

[1]

  • 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.

Customer Product Validation

, , PLoS One, 2016, 11(3):e0150507.

Data from [Data independently produced by , , Clin Cancer Res, 2017, 23(21):6661-6672]

Data from [Data independently produced by , , Neoplasia, 2018, 20(8):838-847]

Data from [Data independently produced by , , Oncogenesis, 2017, 6(4):e307]

Selleck's Capmatinib has been cited by 80 publications

MUC1-C Is a Common Driver of Acquired Osimertinib Resistance in NSCLC [ J Thorac Oncol, 2023, 10.1016/j.jtho.2023.10.017] PubMed: 37924972
Suppression of TNBC metastasis by doxazosin, a novel dual inhibitor of c-MET/EGFR [ J Exp Clin Cancer Res, 2023, 10.1186/s13046-023-02866-z] PubMed: 37924112
FGFR blockade inhibits targeted therapy-tolerant persister in basal FGFR1- and FGF2-high cancers with driver oncogenes [ NPJ Precis Oncol, 2023, 7(1):107] PubMed: 37880373
FGFR blockade inhibits targeted therapy-tolerant persister in basal FGFR1- and FGF2-high cancers with driver oncogenes [ NPJ Precis Oncol, 2023, 7(1):107] PubMed: 37880373
EZH2/hSULF1 axis mediates receptor tyrosine kinase signaling to shape cartilage tumor progression [ Elife, 2023, 12e79432] PubMed: 36622753
MET exon 14 skipping mutation is a hepatocyte growth factor (HGF)-dependent oncogenic driver in vitro and in humanized HGF knock-in mice [ Mol Oncol, 2023, 10.1002/1878-0261.13397] PubMed: 36799689
MET kinase inhibitor reverses resistance to entrectinib induced by hepatocyte growth factor in tumors with NTRK1 or ROS1 rearrangements [ Cancer Med, 2023, 12(5):5809-5820] PubMed: 36416133
MET kinase inhibitor reverses resistance to entrectinib induced by hepatocyte growth factor in tumors with NTRK1 or ROS1 rearrangements [ Cancer Med, 2023, 12(5):5809-5820] PubMed: 36416133
MET Inhibitor Capmatinib Radiosensitizes MET Exon 14-Mutated and MET-Amplified Non-Small Cell Lung Cancer [ bioRxiv, 2023, 10.1101/2023.10.26.564232] PubMed: 37961176
MET exon 14 skipping mutation is a hepatocyte growth factor (HGF)‐dependent oncogenic driverin vitroand in humanizedHGFknock‐in mice. [ Molecular Oncology, 2023, Volume17, Issue11] PubMed: none

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SHIPPING AND STORAGE
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