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Application of combination of TLR7 agonist and tyrosine kinase inhibitor in preparing antineoplastic drugs

A tyrosine kinase and antitumor drug technology, which is used in the application field of TLR7 agonist combined with tyrosine kinase inhibitor in tumor treatment, and can solve the problems of tumor resistance mutation and the like

Active Publication Date: 2016-02-10
SHENZHEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But tumors are prone to drug-resistant mutations, leading to progressive disease progression

Method used

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  • Application of combination of TLR7 agonist and tyrosine kinase inhibitor in preparing antineoplastic drugs
  • Application of combination of TLR7 agonist and tyrosine kinase inhibitor in preparing antineoplastic drugs
  • Application of combination of TLR7 agonist and tyrosine kinase inhibitor in preparing antineoplastic drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Example 1 Anti-tumor experiment of TLR7 agonist combined with tyrosine kinase inhibitor

[0024] (1) Experimental animals and their feeding

[0025] Female 4-week-old Balb / c inbred mice (body weight 16±20 g) were purchased from Guangdong Experimental Animal Center. During the experiment, the mice were kept in the SPF grade animal room of the Medical Department of Shenzhen University.

[0026] (2) Construction of mouse breast cancer model

[0027] 1) Take the 4T1 cells grown in the logarithmic phase, digest the cells with 0.25% trypsin, add 10% FBS complete medium to stop the digestion, then use the complete medium to make cell suspension, adjust the cell concentration to 2×10 6 pieces / ml.

[0028] 2) Take 30 healthy Babl / c pure-line mice, female, 4 weeks old, body weight (16±20g), and divide 2×10 5 One (0.1ml) 4T1 mouse breast cancer cells were subcutaneously injected into the thigh of each mouse, and subcutaneous nodules were palpable in all mice within 3-5 days, a...

Embodiment 2

[0033] Example 2 Western blot detection of expression of TLR7 protein level and activation of NF-κB signaling pathway after TLR7 agonist and tyrosine kinase inhibitor combined stimulation of immune cells in mice

[0034] The experiment was divided into 7 groups, blank control group and positive control group (R848), T7 (10 μM) group, T7 (10 μM) combined with lapatinib (2 μM) group, T7 (10 μM) combined with sunitinib (5 μM) group , lapatinib (abbreviated as LA in the drawings) (2 μM) group, sunitinib (abbreviated as Suni in the drawings) (5 μM) group, and each experiment was repeated 3 times.

[0035] Cell inoculation: take 4-6 week old Balb / c mice, kill them by decapitation, soak them in 700mL of 75% ethanol for 5min, isolate the mouse spleen under aseptic conditions, separate splenic lymphocytes, and adjust the number of cells to 5×l0 6 Each well was placed in a 6-well culture plate, and the volume of each well was 5ml.

[0036] Drug effect: the final concentration of T7 in ...

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Abstract

The invention relates to the technical field of antineoplastic drugs, and in particular discloses application of combination of a TLR7 agonist and a tyrosine kinase inhibitor in preparing the antineoplastic drugs. The TLR7 agonist has a structure as shown in formula (I); and the tyrosine kinase inhibitor, which is lapatinib, has a structure as shown in formula (II). According to embodiments, experimental results show that the TLR7 agonist, in combination with the lapatinib, shows a significant synergistic treatment effect on treating a model of mice mammary cancer.

Description

technical field [0001] The invention relates to the technical field of antitumor drugs, in particular to the application of TLR7 agonists and tyrosine kinase inhibitors in combination in tumor treatment. Background technique [0002] Tumor treatment is not only a worldwide problem, but also a major challenge for the medical community. Clinically applied tumor treatment is mainly to remove solid mass of tumor through surgery, physical therapy and chemotherapy. While physical therapy and chemotherapy kill a large number of cancer cells, they also kill a large number of normal cells in the body and severely damage the immune system, which greatly reduces the patient's ability to fight cancer, and the remaining drug-resistant cancer cells will become even crazier Proliferate, and there is the possibility of secondary. Simultaneous radiotherapy and chemotherapy will not only bring great pain to patients, but also cause a series of toxic and side effects. These traditional trea...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/517A61P35/00A61K31/522
Inventor 靳广毅高宁宁王竹林
Owner SHENZHEN UNIV
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