| Name | Capmatinib |
| Description | Capmatinib (INCB28060) is an orally bioavailable inhibitor of the proto-oncogene c-Met (HGFR)with potential antineoplastic activity. |
| Cell Research | 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.(Only for Reference) |
| 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, 5 mM 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 |
| In vitro | In a c-MET-dependent mouse tumor model, the oral administration of INCB28060 (0.03 mg/kg) effectively inhibited tumor growth. |
| In vivo | In tumor cells, INCB28060 inhibits cell proliferation and survival by downregulating c-MET phosphorylation and the signaling pathways mediated by c-MET. |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility Information | DMSO : 4.12 mg/mL (10 mM), Sonication is recommended.
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| Keywords | orally active | Capmatinib | Apoptosis | ATP competitive | H441 | Balb/c nu/nu mice | NVP-INC-280 | inhibit | INC 280 | c-Met/HGFR | Inhibitor | INC280 | SNU-5 | INCB 28060 | NVP-INC 280 | U-87MG | INCB-28060 | S114 |
| Inhibitors Related | Stavudine | 5-Fluorouracil | Acetylcysteine | Myricetin | Sodium 4-phenylbutyrate | L-Ascorbic acid | Dextran sulfate sodium salt (MW 4500-5500) | Metronidazole | Sorafenib | Tributyrin |
| Related Compound Libraries | Highly Selective Inhibitor Library | Bioactive Compound Library | Membrane Protein-targeted Compound Library | Tyrosine Kinase Inhibitor Library | Kinase Inhibitor Library | Inhibitor Library | FDA-Approved Kinase Inhibitor Library | Bioactive Compounds Library Max | Anti-Cancer Active Compound Library | Anti-Cancer Drug Library |
United States
