Tepotinib

製品コードS7067 バッチS706703

印刷

化学情報

Chemical Structure Synonyms EMD 1214063, MSC2156119 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C29H28N6O2
分子量 492.57 CAS No. 1100598-32-0
Solubility (25°C)* 体外 DMSO (warmed with 50ºC water bath) 4.5 mg/mL (9.13 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Tepotinib is a potent and selective c-Met inhibitor with IC50 of 4 nM, >200-fold selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer. Tepotinib (EMD 1214063) induces autophagy. Phase 1.
in vitro EMD 1214063 inhibits HGF-induced c-Met phosphorylation in A549 cells with IC50 of 6 nM. Treatment with this compound induces a marked reduction of c-Met–constitutive phosphorylation in EBC-1 cells with IC50 of 9 nM. It effectively blocka phosphorylation of the major downstream effectors of the c-Met enzyme, such as Grb2, Gab1, Sos, PLCγ, and phosphoinositide 3-kinase, in EBC-1, MKN-45, and Hs746T cells in the range of 1 to 10 nM. This chemical considerably inhibits the viability of MKN-45 cells with IC50 of less than 1 nM. Treatment with it (as low as 0.1 nM) inhibits HGF-induced NCI-H441 cell migration, whereas concentrations of 100 nM to 1 μM almost completely prevents it. [1]
in vivo EMD 1214063 treatment, at doses of 10 mg/kg or more, results in more than 90% inhibition of c-Met phosphorylation in Hs746T xenograft tumor for a period of at least 72 hours. This compound induces more than 50% reduction of cyclin D1 expression, which persists after 96 hours upon treatment with doses of 100 mg/kg. A transient induction of p27 and cleaved caspase-3 are also observed upon treatment with this chemical. It (15 mg/kg, daily) treatment induces complete regression of gastric carcinoma xenografts Hs746T, in which c-Met is amplified, overexpressed, and activated in a ligand-independent fashion. [1]

プロトコル(参考用のみ)

キナーゼアッセイ c-Met kinase assay
Kinase inhibition by EMD 1214063 (1 and 10μM) is assessed in vitro using a panel of 242 different kinases. Biochemical activity is measured in a flash-plate assay. His6-tagged recombinant human c-Met kinase domain (Aa 974–end; 20 ng) and biotinylated poly-Ala-Glu-Lys-Tyr (6:2:5:1; 500 ng) are incubated with or without the test compound for 90 minutes at room temperature in 100 μL buffer containing 0.3 μCi33P-ATP, 2.5 μg polyethylene glycol 20.000, and 1% dimethyl sulfoxide (DMSO). Radioactivity is measured with a TopCount microplate scintillation and luminescence counter.
動物実験 動物モデル Human gastric carcinoma xenografts Hs746T
投薬量 15 mg/kg
投与方法 daily

参考

  • https://pubmed.ncbi.nlm.nih.gov/23553846/

カスタマーフィードバック

Data from [Data independently produced by , , Cell Research, 2015, 25: 445-458]

Data from [Data independently produced by , , Biochim Biophys Acta Mol Basis Dis, 2018, 1864(3):793-803]

Data from [Data independently produced by , , J Virol, 2016, 90(14):6412-29. ]

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：

PD-L1 regulates c-MET phosphorylation and contributes to MET-dependent resistance to osimertinib in EGFR-mutant NSCLC [ J Biomed Sci, 2025, 32(1):94] PubMed: 41068729
PTEN loss and ERBB2/ERBB3-mediated AKT reactivation drive resistance to MET inhibition in MET-amplified hepatocellular carcinoma [ Cell Oncol (Dordr), 2025, 10.1007/s13402-025-01097-y] PubMed: 40991144
Efficacy of amivantamab, a bi-specific antibody targeting EGFR and MET, in ALK-rearranged non-small-cell lung cancer cell lines [ Lung Cancer, 2025, 201:108415] PubMed: 39922174
TWIST1 is a critical downstream target of the HGF/MET pathway and is required for MET driven acquired resistance in oncogene driven lung cancer [ Oncogene, 2024, 10.1038/s41388-024-02987-5] PubMed: 38485737
Comparison of Tepotinib, Paclitaxel, or Ramucirumab Efficacy According to the Copy Number or Phosphorylation Status of the MET Gene: Doublet Treatment versus Single Agent Treatment [ Int J Mol Sci, 2024, 25(3)1769] PubMed: 38339049
Comparison of Tepotinib, Paclitaxel, or Ramucirumab Efficacy According to the Copy Number or Phosphorylation Status of the MET Gene: Doublet Treatment versus Single Agent Treatment [ Int J Mol Sci, 2024, 25(3)1769] PubMed: 38339049
Bladder cancer organoids as a functional system to model different disease stages and therapy response [ Nat Commun, 2023, 14(1):2214] PubMed: 37072390
Bladder cancer organoids as a functional system to model different disease stages and therapy response [ Nat Commun, 2023, 14(1):2214] PubMed: 37072390
"Proteotranscriptomic analysis of advanced colorectal cancer patient derived organoids for drug sensitivity prediction" [ J Exp Clin Cancer Res, 2023, 42(1):8] PubMed: 36604765
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

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。

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