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Tepotinib

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Chemical Structure| 1100598-32-0 同义名 : EMD 1214063;MSC2156119
CAS号 : 1100598-32-0
货号 : A242274
分子式 : C29H28N6O2
纯度 : 99%+
分子量 : 492.572
MDL号 : MFCD18452823
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：

IP 5% DMSO+water 1 mg/mL clear

PO 0.5% CMC-Na 20 mg/mL suspension

生物活性
描述 The overexpression and activation of the Met receptor and its ligand HGF (hepatocyte growth factor) are associated with a wide variety of human malignancies, as well as the tumor invasion. Tepotinib is a selective c-Met inhibitor with IC50 value of 3nM (measured by kinase activity), over 200-fold against IRAK4, TrkA, Axl, IRAK1, Mer, TrkB and Ron. Exposure to Tepotinib resulted in inhibition of HGF-induced c-Met phosphorylation with IC50 of 6nM in A549 cells and a significant reduction of c-Met–constitutive phosphorylation with IC50 of 9nM in EBC-1 cells. The suppression of phosphorylation of the c-Met pathway, including Gab-1, Akt and Erk1/2, can also be observed. This kinase inhibition can also be observed in in vivo study as a single dose of 30mg/kg Tepotinib caused inhibition of c-Met auto-phosphorylation both in tumors derived from Hs746T xenograft mice, along with decreased cyclin D1 and inducing p27 expression, within 48h. As prediction, daily administration at dose of 6mg/kg significantly inhibited tumor growth in mice bearing human HGF-dependent pancreatic carcinoma cell line KP-4, while suppressed tumor growth at dose of 15mg/kg. In another model mice bearing subcutaneous tumors derived from the HGF-independent human lung cancer cell line EBC-1, the tumor growth by Tepotinib can be observed at dose of 25 or 50mg/kg, when the tumor suppression can be observed at dose of 200mg/kg[1].
作用机制 Tepotinib is an ATP-competitive inhibitor.[2]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human A549 cells Function assay 45 mins Inhibition of c-Met kinase in human A549 cells assessed as inhibition of phosphorylation after 45 mins by electrochemiluminescence assay, IC50=12 nM 25736998
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.03mL

0.41mL

0.20mL

10.15mL

2.03mL

1.02mL

20.30mL

4.06mL

2.03mL
参考文献

[1]Bladt F, Faden B, et al. EMD 1214063 and EMD 1204831 constitute a new class of potent and highly selective c-Met inhibitors. Clin Cancer Res. 2013 Jun 1;19(11):2941-51.

[2]Bill KL, Garnett J, et al. The hepatocyte growth factor receptor as a potential therapeutic target for dedifferentiated liposarcoma. Lab Invest. 2015 Aug;95(8):951-61.