Lenvatinib 是一种口服具有活性的，多靶点酪氨酸激酶抑制剂，能够抑制血管内皮生长因子受体(VEGFR1-3)，成纤维细胞生长因子受体(FGFR1-4)，干细胞因子受体(KIT)，血小板衍生生长因子受体(PDGFR)，转染期间重排(RET)，具有效抗癌的作用。

Lenvatinib is a Kinase Inhibitor. The mechanism of action of lenvatinib is as a Receptor Tyrosine Kinase Inhibitor.

与血管内皮生长因子抗体和伊马替尼处理相比,100 mg/kg E7080处理降低微脉管密度效果更好.用30和100 mg/kg E7080口服给药处理H146 移植瘤模型,可以剂量依赖性抑制H146肿瘤生长,100 mg/kg时导致肿瘤退化

体外受体酪氨酸和丝/苏氨酸激酶实验中,E7080抑制Flt-1,KDR和Flt-4,IC50分别为22,4.0和5.2 nM。最新研究显示,1 μM和10 μM E7080通过抑制FGFR和PDGFR信号通路明显抑制细胞迁移和入侵。E7080有效抑制血管生成,也明显抑制VEGF/KDR和SCF/KIT信号通路。E7080也抑制FGFR1和PDGFR酪氨酸激酶,作用于FGFR1,PDGFRα和PDGFRβ时,IC50分别为46,51和100 nM。E7080分别作用于由血管内皮生长因子和血管内皮生长因子-C刺激的HUVECs,有效抑制VEGFR2和VEGFR3磷酸化,IC50分别为0.83 nM和0.36 nM。

In vitro kinase assay [1]: Tyrosine kinase assays are performed by HTRF (KDR, VEGFR1, FGFR1, c-Met, EGFR) and ELISA (PDGFRβ), using the recombinant kinase domains of receptors. In both assays, 4 μL of serial dilutions of E7080 are mixed in a 96-well round plate with 10 μL of enzyme, 16 μL of poly (GT) solution (250 ng) and 10 μL of ATP solution (1 μM ATP) (final concentration of DMSO is 0.1%). In wells for blanks, no enzyme is added. In control wells no test article is added. The kinase reaction is initiated by adding ATP solution to each well. After 30-minute incubation at 30°C, the reaction is stopped by adding 0.5 M EDTA (10 μL/well) to the reaction mixture in each well. Dilution buffer adequate to each kinase assay is added to the reaction mixture. In the HTRF assay, 50 μL of the reaction mixture is transferred to a 96-well 1/2 area black EIA/RIA plate, HTRF solution (50 μL/well) is added to the reaction mixture, and then kinase activity is determined by measurement of fluorescence with a time-resolved fluorescence detector at an excitation wavelength of 337 nm and an emission wavelengths of 620 and 665 nm. In the ELISA, 50 μL of the reaction mixture is incubated in avidin coated 96-well polystyrene plates at room temperature for 30 minutes. After washing with wash buffer, PY20-HRP solution (70 μL/well) is added and the reaction mixture is incubated at room temperature for 30 minutes. After washing with wash buffer, TMB reagent (100 μL/well) is added to each well. After several minutes (10–30 minutes), 1 M H3PO4 (100 μL/well) is added to each well. Kinase activity is determined by measurement of absorbance at 450 nm with a microplate reader.

HUVECs (1,000 cells in each well in serum-free medium containing 2% fetal bovine serum) and L6 rat skeletal muscle myoblasts (5,000 cells in each well in serum-free DMEM) are dispensed in a 96-well plate and incubated overnight. E7080 and either VEGF (20 ng/mL) or FGF-2 (20 ng/mL) containing 2% fetal bovine serum and PDGFβ (40 ng/mL) are added to each well. Cells are incubated for 3 days and then the ratios of surviving cells are measured by WST-1 reagent. For proliferation assay, samples are duplicated and three separate experiments are done. (Only for Reference)

417716-92-8

C21H19ClN4O4

426.86

仑伐替尼;E7080

DMSO:38 mg/mL (89 mM)
Ethanol:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years