Lenvatinib (E7080) (Synonyms: E-7080, ER-203492-00)

Preparation Method

4μL of serial dilutions of Lenvatinib (E7080) were mixed in a 96-well round plate with 10μL of enzyme (KDR), 16μL of poly (GT) solution (250 ng) and 10μL of ATP solution (1μmol/L ATP) (final concentration of DMSO was 0.1%).The kinase reaction was initiated by adding ATP solution to each well. After 30-min incubation at 30°C, the reaction was stopped by adding 0.5 mol/L EDTA (10μL/well) to the reaction mixture in each well. HTRF solution (50μL/well) was added to the reaction mixture, and then kinase activity was determined by measurement of fluorescence with a time-resolved fluorescence detector at an excitation wavelength of 337 nm and an emission wave-lengths of 620 and 665 nm.

Reaction Conditions

4μL,30 min

Applications

Lenvatinib (E7080) inhibited KDR with IC₅₀ values of 4.0 nM.

Cell lines

8505C and TCO1 cell

Preparation Method

The cells were grown in 96-well microplates in a final volume of 100 μL culture medium per well. The cells were incubated with 0.1 to 50 μM Lenvatinib (E7080) for 48 h. Then, 50 μL of the XTT labeling mixture was added to each well to a final XTT concentration of 0.3 mg/mL. After incubation of the microplate for 4 h in 5% CO2 at 37 °C in a humidified incubator, the formazan dye formed was quantified using a scanning multiwell spectrophotometer.

Reaction Conditions

0.1 to 50 μM Lenvatinib (E7080) for 48 h

Applications

The half-maximal inhibitory concentrations (IC₅₀) for Lenvatinib (E7080) treatment of 8505C and TCO1 cells were 24.26 and 26.32 μM, respectively.

Animal models

Female BALB/c nude mice (8–12 weeks old, 20–25 g)

Preparation Method

H146 tumor cells (6.5×10⁶) were implanted subcutaneously into the flank region of mice. Twelve days after inoculation, mice were randomized into control (n=12) and treatment groups (n=6) and this point in time was identified as day 1. Lenvatinib (E7080) were suspended in 0.5% methylcellulose and saline, and administered orally twice a day for Lenvatinib (E7080) from day 1 to day 21. Tumor volume was measured on the indicated days and calculated.

Dosage form

Administer orally twice a day for Lenvatinib (E7080)

Applications

Oral administration of Lenvatinib (E7080) inhibited the growth of H146 tumor at 30 and 100 mg/kg in a dose-dependent manner and caused tumor regression at 100 mg/kg.

References:

[1]. Matsui J, Yamamoto Y, Funahashi Y, Tsuruoka A, Watanabe T, Wakabayashi T, Uenaka T, Asada M. E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer. 2008 Feb 1;122(3):664-71.

[2]. Enomoto K, Hirayama S, Kumashiro N, Jing X, Kimura T, Tamagawa S, Matsuzaki I, Murata SI, Hotomi M. Synergistic Effects of Lenvatinib (E7080) and MEK Inhibitors against Anaplastic Thyroid Cancer in Preclinical Models. Cancers (Basel). 2021 Feb 18;13(4):862.