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受注：045-509-1970 |
技術サポート：[email protected] 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
化学情報
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Synonyms | INC280, NVP-INC280, INCB28060 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C23H17FN6O |
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| 分子量 | 412.42 | CAS No. | 1029712-80-8 | |
| Solubility (25°C)* | 体外 | DMSO | 14 mg/mL (33.94 mM) | |
| Water | Insoluble | |||
| Ethanol | Insoluble | |||
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* <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. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | 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. |
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| 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] |
| 特徴 | Inactive against RONβ, another member of the c-MET RTK family, as well as EGFR and HER-3 (members of the EGFR RTK family). |
プロトコル(参考用のみ)
| キナーゼアッセイ | c-Met Kinase Assay | |
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| 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 | ||
| 細胞アッセイ | 細胞株 | H441 cells |
| 濃度 | 0.24, 1, 4, 16, 63 nM | |
| 反応時間 | 24 hours | |
| 実験の流れ | 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. |
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| 動物実験 | 動物モデル | 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). |
| 投薬量 | 3, 10, 30 mg/kg | |
| 投与方法 | INCB28060 is orally dosed, twice each day. | |
参考
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カスタマーフィードバック
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, , PLoS One, 2016, 11(3):e0150507.
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Data from [Data independently produced by , , Clin Cancer Res, 2017, 23(21):6661-6672]
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Data from [Data independently produced by , , Neoplasia, 2018, 20(8):838-847]
Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| 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 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。