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Application of compound LY2228820 to preparation of sensitizer of anti-tumor chemotherapeutic drug and anti-tumor pharmaceutical composition

A technology of LY2228820 and anti-tumor drugs, applied in the field of medicine, can solve the problems of patients' condition deterioration, chemotherapy failure, death and other problems

Inactive Publication Date: 2017-11-17
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, drug resistance of tumors often leads to the failure of chemotherapy, which leads to the deterioration of the patient's condition and even death.

Method used

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  • Application of compound LY2228820 to preparation of sensitizer of anti-tumor chemotherapeutic drug and anti-tumor pharmaceutical composition
  • Application of compound LY2228820 to preparation of sensitizer of anti-tumor chemotherapeutic drug and anti-tumor pharmaceutical composition
  • Application of compound LY2228820 to preparation of sensitizer of anti-tumor chemotherapeutic drug and anti-tumor pharmaceutical composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] The killing effect of chemotherapy drugs on drug-resistant cell line SK-cbt-2 and its parental SK-hep-1.

[0036] (1) Experimental method

[0037] SK-cbt-2 was inoculated on 100mm culture dishes, cultured for 72 hours, and the culture medium was removed; digested with 0.25% trypsin, collected cells, counted cells, prepared a single cell suspension with a concentration of 20,000 cells / ml, and inoculated 0.2ml single cells in each well. The cell suspension was transferred to a 96-well plate, and the total number of cells per well was 4000; cultured overnight, and the corresponding chemotherapeutic drugs were added for treatment; the treatment concentration of docetaxel was 0, 0.5, 1, 2, 5, 10, 20, 50 , 100, 200nM; the treatment concentration of paclitaxel was 0, 1, 2, 5, 10, 20, 50, 100, 200, 500nM; the treatment concentration of vinorelbine was 0, 5, 10, 20, 50, 100, 200, 500, 1000, 2000nM; Doxorubicin treatment concentration is 0, 20, 50, 100, 200, 500, 1000, 2000, 500...

Embodiment 2

[0046] LY2228820 was tested for cytotoxicity of SK-cbt-2, and a safe concentration without obvious cytotoxicity was selected.

[0047] (1) Experimental method

[0048]SK-hep-1 and SK-cbt-2 were inoculated on 100mm culture dishes, cultivated for 72 hours, and removed the culture medium; digested with 0.25% trypsin, collected cells, counted cells, and prepared single cell suspensions with a concentration of 20,000 cells / ml, respectively Inoculate 0.2ml of single-cell suspension into each well of a 96-well plate, the total number of cells per well is 4000; culture overnight, add LY2228820 (treatment concentration is 0, 10, 20, 50, 100, 200, 500, 1000, 2000 , 5000nM) for 72h, removed the supernatant, added 0.2ml DMSO, and detected the OD value with a microplate reader at a wavelength of 570nM.

[0049] (2) Experimental results

[0050] see results figure 1 , after 1000nM LY2228820 treatment for 72 hours, the viability of SK-hep-1 and SK-cbt-2 cells were still greater than 90%. ...

Embodiment 3

[0052] LY2228820 significantly enhanced the killing effect of docetaxel on SK-cbt-2 cells.

[0053] (1) Experimental method

[0054] SK-cbt-2 was inoculated on 100mm culture dishes, cultured for 72 hours, and the culture medium was removed; digested with 0.25% trypsin, collected cells, counted cells, prepared a single cell suspension with a concentration of 20,000 cells / ml, and inoculated 0.2ml single cells in each well. The cell suspension was transferred to columns 2-11 of a 96-well plate, and the total number of cells per well was 4000; cultured overnight, no reagent was added to column 2, and 500nM LY2228820 was added to each well of cells in columns 3-11, and at the same time Add 2, 5, 10, 20, 50, 100, 200, 500, 1000nM) docetaxel in sequence respectively, co-treat for 72 hours, remove the supernatant, add 0.2ml DMSO, and detect the OD value with a microplate reader at a wavelength of 570nM.

[0055] (2) Experimental results

[0056] see results figure 2 , 500nM LY2228...

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Abstract

The invention discloses an application of compound LY2228820 to preparation of a sensitizer of an anti-tumor chemotherapeutic drug and anti-tumor pharmaceutical composition. The anti-tumor pharmaceutical composition comprises the chemotherapeutic drug and the sensitizer, wherein the sensitizer is the compound LY2228820. Research finds that the p38 kinase inhibitor ceritinib can serve as the sensitizer of the anti-tumor chemotherapeutic drug and has the advantages that the resistance of tumor to the chemotherapeutic drug can be overcome and the curative effect of the chemotherapeutic drug on drug-resistant tumor cells is enhanced remarkably when combined with the chemotherapeutic drug for use, and novel ways and means are provided for effective tumor treatment.

Description

technical field [0001] The present invention relates to the field of medicine, in particular to the application of compound LY2228820 in the preparation of antitumor chemotherapeutic drug sensitizer and antitumor drug composition. Background technique [0002] Cancer is the number one "killer" that seriously threatens the life and health of our people, and has become a public health problem that needs to be solved urgently! The latest research shows that new cancer cases and deaths in my country are increasing year by year. Among them, there were about 4.292 million new cases of invasive cancer in 2015, with an average of about 12,000 new cases per day; at the same time, there were 2.814 million cancer deaths in 2015, with an average of about 12,000 new cases per day. 7,500 people died from cancer. [0003] At present, the main treatment methods for malignant tumors include surgery, radiotherapy and chemotherapy. For patients diagnosed with advanced tumors and patients with...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/437A61P35/00
CPCA61K45/06A61K31/437A61K2300/00
Inventor 蒋东海
Owner ZHEJIANG UNIV
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