Use of quinazoline compounds as drugs for treating cancer with EGFRv3 activation mutation
A technology of quinazolines and compounds, which is applied in the direction of medical preparations containing active ingredients, drug combinations, organic active ingredients, etc., can solve the problems of EGFRv3 mutation drugs on the market, and achieve improved effectiveness, good curative effect, and cost reduction Effect
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0020] This embodiment relates to the use of quinazoline derivatives (I) in the inhibition of phosphorylation of EGFRv3 mutations
[0021] In western blot experiments, cells were cultured to 2×10 5 / mL, treated with the compound concentration (0, 10, 100, 1000nM) described in this paper for 24 hours, the culture medium was discarded, buffer was added, separated by ultrasonic centrifugal electrophoresis, immunoblotting and color development, the phosphorylation of EGFRv3 was detected by quinazoline Derivative (I) inhibits, figure 1 It is shown that the quinazoline derivative (I) has good biological activity, and specifically targets cancer mediated by EGFRv3 phosphorylation.
Embodiment 2
[0023] This embodiment relates to quinazoline derivatives (I) in the tumor transplantation animal model of the brain tumor of the EGFRv3 mutation in the primary tumor tissue of the subcutaneous mouse patient
[0024] The patient's primary tumor tissue (brain tumor) was planted subcutaneously in the mouse, and the tumor grew to about 150mm 3 Start medication afterward, treat for three weeks.
[0025] In the drug effect experiment of the tumor transplantation animal model of the brain tumor with EGFRv3 mutation in the primary tumor tissue of the mouse subcutaneous patient, the first group was the control group without any drug. The second group of quinazoline derivatives (I) single drug, 3 mg / kg, orally, twice a day, the third group of quinazoline derivatives (I) single drug, 10 mg / kg, orally, twice a day Time, the fourth group of quinazoline derivatives (I) single drug, 20 mg / kg, orally, twice a day. Compared with the first group (control group), the drug groups (second, thir...
Embodiment 3
[0027] In vitro inhibition of patient tissue cells with EGFRv3 mutation
[0028] 3.5 mL of 2 x 10 5 / mL of cells, mix 6.5mL of 1v / v% methylcellulose, add 90μL to a 96-well plate, and incubate overnight. On the first day, take 10 μL to read the number of cells, add 100 μL CellTiter-Glo reagent to lyse the cells, and use EnVision Multi Label Reader to read the fluorescence. Add different concentrations of compounds (0.33, 1, 3.3, 10, 33, 100, 333, 1000, 3333, 10000 nM), seven days later, add 100 μL The reagents were used to lyse the cells in each well, and the fluorescence was read using EnVision Multi Label Reader to obtain the inhibition rate of the cells.
[0029] Survival rate (%)=(test result of drug concentration group-test result of nutrient solution control group) / (test result of no drug concentration group-test result of nutrient solution control group)×100%.
[0030] IC 50 <100nM.
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More