Novel application of tyrosine kinase inhibitor DCC-2036

A technology of DCC-2036 and tyrosine kinase, which can be used in drug combinations, anti-tumor drugs, etc., and can solve problems such as triple-negative breast cancer that has not been seen

Inactive Publication Date: 2017-06-13
THE FIRST AFFILIATED HOSPITAL HENGYANG MEDICAL SCHOOL UNIV OF SOUTH CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But there is no application of DCC-2036 in the treatment of triple-negative breast cancer

Method used

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  • Novel application of tyrosine kinase inhibitor DCC-2036
  • Novel application of tyrosine kinase inhibitor DCC-2036
  • Novel application of tyrosine kinase inhibitor DCC-2036

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Example 1: Effect of DCC-2036 on proliferation of triple-negative breast cancer cell lines MDA-MB-231 and HS-578T

[0041] The MTS method was used to observe the effect of DCC-2036 on the proliferation of TNBC cell lines at the cellular level. PR+, HER2-) breast cancer cell line MCF-7 and basal / triple-negative breast non-tumor epithelial cell line MCF-10A were seeded in 96-well plates, 3×10 per well 3 cells. After 24 hours, the cells adhered to the wall, and a blank group (only culture medium was added), a control group and a drug series group were set up, and three replicate wells were set up in each group, and the volume of each well was 100 μL. The culture was terminated at 72 hours. 4 hours before terminating the culture, add 20 μL / well of MTS / PMS. Continue culturing for 4 hours, and read the absorbance value (A value) at 490 nm with a microplate reader. Calculate the cell viability (Cell Viability) according to the following formula, cell viability=(A value of ...

Embodiment 2

[0046] Example 2 Effect of DCC-2036 on cell cycle distribution

[0047]TNBC cells (MDA-MB-231) were treated with different concentrations (0 μM and 3.75 μM) of DCC-2036 for 30 hours, then digested with trypsin to collect the cells, washed twice with PBS, discarded the supernatant, and added 1ml of 70% pre-cooled ethanol medium, blow and beat evenly, and fix at 4°C for more than 12 hours. Wash with PBS twice to remove ethanol, resuspend the cells in 0.5ml PBS after centrifugation, add propidium iodide (PI) and RNaseA to a final concentration of 50g / ml, incubate at 37°C for 30 minutes, and measure the cell cycle distribution by flow cytometry. see results figure 2 .

[0048] figure 2 The results showed that DCC-2036 could induce G1 arrest in MDA-MB-231 cells. 3.75μM DCC-2036 treatment of MDA-MB-231 cells for 30 hours increased the G1 phase of the cells.

Embodiment 3

[0049] Example 3: Effect of DCC-2036 on apoptosis of TNBC cell lines

[0050] The effects of different concentrations of DCC-2036 on the apoptosis of TNBC cell lines were detected by AnnexinV-FITC / PI double-staining flow cytometric detection technology. The specific method is: TNBC cell line MDA-MB-231 cells, HS-578T cells and Luminal A subtype cell line MCF-7 cells were treated with DCC-2036 at concentrations of 0 μM, 2.5 μM, 3.75 μM, and 5 μM (and 10 μM) respectively. After 24 hours, digest and collect cells, wash with 1×Binding buffer, add Annexin V-FITC dye and incubate for 20 minutes in the dark. PI dye was added before detection on the flow cytometer. The apoptosis rate of cells was evaluated by FACS Calibur flow cytometer and CellQuest Pro software (Becton Dickinson), the results are shown in Figure 3-5 .

[0051] Figure 3-5 The results show that DCC-2036 can induce the apoptosis of TNBC cell lines MDA-MB-231, HS-578T and Luminal A subtype cell line MCF-7 in a dos...

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Abstract

The invention belongs to the field of medicinal chemistry, provides novel application of a tyrosine kinase inhibitor DCC-2036, and in particular discloses application of the tyrosine kinase inhibitor DCC-2036 in preparation ofmedicines for preventing or treating triple negative breast cancer. Tests show that the tyrosine kinase inhibitor DCC-2036 is capable of inhibiting proliferation and invasion and metastasis of TNBC(Triple Negative Breast Cancer) cell systems MDA-MB-231 and HS-578T, and moreover the inhibition function of the tyrosine kinase inhibitor DCC-2036 upon cell proliferation is prior to those of most TNBCclinicalfirst-line treatment medicines. Meanwhile, tests further show thatreceptor tyrosine kinaseAXL is a key target of DCC-2036 to take effects into play in TNBC cells, the tyrosine kinase inhibitor DCC-2036 targets AXL and further regulates downstream signal paths to take the anti-tumor function into play in the TNBC and is good in targeted therapy specificity and remarkable in effect, and normal tissue is generally not damaged.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to the new application of tyrosine kinase inhibitor DCC-2036, in particular to the application of tyrosine kinase inhibitor DCC-2036 in the preparation of drugs for preventing or treating triple-negative breast cancer. Background technique [0002] The female mammary gland is composed of skin, fibrous tissue, mammary glands and fat. Breast cancer is a malignant tumor that occurs in the mammary gland epithelial tissue. Triple negative breast cancer (TNBC) refers to breast cancer in which the results of immunohistochemical examination of cancer tissue are negative for estrogen receptor (ER), progesterone receptor (PR) and proto-oncogene Her-2. . This type of breast cancer accounts for 10.0% to 20.8% of all breast cancer pathological types. There are about one million new cases of breast cancer in the world every year, and more than 170,000 patients are triple-negative b...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4709A61P35/00A61P35/04
CPCA61K31/4709
Inventor 申莹莹祖旭宇蒋宇扬何俊张存龙曹仁贤刘江华
Owner THE FIRST AFFILIATED HOSPITAL HENGYANG MEDICAL SCHOOL UNIV OF SOUTH CHINA
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