| Description |
TAS-120 is a novel, potent and highly selective FGFR inhibitor, used for antitumor treatment.
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| Related Catalog |
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| Target |
FGFR
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| In Vivo |
TAS-120 (3, 30, 100 mg/kg/day, p.o.) exerts an anti-tumor effect in mice. TAS-120 shows anti-tumor effect by administering at moderate intervals, such as intermittent administration of every other day dosing and 2 times/week, and reducing the sustained elevation and weight suppression blood phosphorus level, and take a antitumor effective as daily administration[1].
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| Kinase Assay |
In the inhibitory activity measurement of compounds it is first serially diluted as with test compound dimethyl sulfoxide (DMSO) to 20 times the concentration of the final concentration. Then, reaction buffer (15 mM Tris-HCl pH7.5,0.01% Tween-20, 2 mM DTT) purified human FGFR2 protein in, FL-Peptide 22 (final concentration 1.5 μM), magnesium chloride (final concentration 5 mM), ATP (final concentration is final concentration and incubated with the kinase reaction for 120 minutes at 25°C by adding 5%) of 75 μM) and test compound in DMSO (DMSO. EDTA diluted in (final concentration 30 mM) are the kinase reaction is stopped by adding. Finally, LabChip (TM) 3000 system (an excitation wavelength of 488 nm, detection wavelength 530 nm) separating the phosphorylated peptide and a non-phosphorylated peptide by measuring the amount of each, and phosphorus from the ratio to determine the oxidation reaction amount is defined the compound concentration able to inhibit the phosphorylation reaction 50% IC50 value (nM).
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| Cell Assay |
FGFR overexpressing human gastric cancer cell line OCUM-2MD3 cells, Dulbecco's Modified Eagle containing 10% fetal bovine serum (FBS) in medium (DMEM), are routinely passaged in cell density not exceeding 80%. To initiate the testing of the cytostatic activity, the OCUM-2MD3 cells are suspended in the above DMEM medium, after the number of cells per well are seeded to be 3,000 in each well of 96-well flat-bottom plates, it is cultured for one day at 37°C in an incubator containing 5% carbon dioxide gas. The next day, it is stage diluted to 100 times the concentration of the final concentration of the test compound in DMSO. Diluted with a medium of DMSO solution is used for the culture of the test compound which is added to a final concentration of DMSO in each well of a culture plate of cells of 0.5%, 5% carbon dioxide gas incubator containing it is cultured for 72 hours at 37°C. Measurement of cell number after the time and 72 hours of culturing the addition of the test compound using a cell counting kit-8, is carried out in accordance with the recommended protocols Dojindo Laboratories. It is added a reagent kit containing in each plate is performed for a predetermined time color reaction at 37°C in incubator containing 5% carbonic acid gas. After completion of the reaction, using a microplate reader and the absorbance is measured at a wavelength of 450 nm. Calculating a growth inhibition rate from the following formula, it is determined the concentration of the test compound (GI50 (nM)) for 50% inhibition.
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| Animal Admin |
It is transplanted to the right chest of the anti-tumor effect human gastric cancer strain (OCUM-2MD3) the old 6-week-old male nude rats with intermittent administration schedule in Test Example 7 rat. Measuring the major axis of tumor (mm) and minor axis (mm) after tumor implantation, the tumor volume: After calculating the (tumor volume TV), allocates the mouse average TV each group to be equal in each group, the the days that are conducted grouped the (n=5) is the day 0. TAS-120 3 mg/kg/day, 30 mg/kg/day, is prepared so as to 100 mg/kg/day, 3 mg/kg/day is daily administered orally, 30 mg/kg/day is administered orally every other day, 100 mg/kg/day is performed oral administration of 2 time/week from day 1, provided with the evaluation period of 14 days, the final valuation date it is day 15.
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| References |
[1]. Hiroaki OCHIIWA, et al. Antitumor drug for intermittent administration of fgfr inhibitor. WO 2015008839 A1.
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