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Use of lauryl diamine derivatives in preparation of drugs for treatment of breast cancer

A technology of lauryl diamine and derivatives, applied in the field of medicine, can solve the problems of uncontrollable disease and lack of breast cancer cells.

Inactive Publication Date: 2019-01-18
柴梦莹
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Studies in recent years have shown that taking tamoxifen or exemestane can reduce the incidence of breast cancer in high-risk groups, but the drug only targets the specific regulation of breast hormone secretion and does not have any specific killing function for breast cancer cells. Moreover, when cancer cells have spread or infinitely proliferated, chemotherapy, mastectomy and various targeted drugs can no longer control the disease, and we can only wait for the cancer to spread and cause the patient to die
[0004] At present, there is no specific targeted small molecule drug that clearly targets the carcinogenesis mechanism of breast cancer and can effectively inhibit the growth of cancer cells.

Method used

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  • Use of lauryl diamine derivatives in preparation of drugs for treatment of breast cancer
  • Use of lauryl diamine derivatives in preparation of drugs for treatment of breast cancer
  • Use of lauryl diamine derivatives in preparation of drugs for treatment of breast cancer

Examples

Experimental program
Comparison scheme
Effect test

experiment example 1

[0054] Experimental Example 1 Inhibition of Test Compounds Binding to 12G5 Antibody CXCR4 Receptor Experiment

[0055] CXCR4 is a cell membrane biomarker of cancer cell proliferation and malignant division, and SDF-1 is a natural chemokine and agonist of CXCR4. Therefore, by effectively inhibiting the binding of CXCR4 to SDF-1, the signal of CXCR4 can be inhibited, normal cell physiological functions can be maintained, and hematopoietic differentiated cells (immune cells and leukocytes) can be prevented from entering the malignant proliferation program. When CXCR4 is stimulated by a signal that is too strong, whether it is positive regulation or negative regulation will cause CXCR4 intracellular signal regulation disorders, resulting in imbalanced cell growth.

[0056] 12G5 is a general commercial antibody that recognizes CXCR4 as a murine monoclonal antibody. 12G5 antibody has strong binding affinity to CXCR4 and can be used to recognize CXCR4.

[0057] In this experiment, ...

experiment example 2

[0066] Experimental example 2 Specific recognition experiment of test compound to CXCR4

[0067] The CCR5 receptor is a specific chemokine receptor expressed by T lymphocytes in the activated state. For T lymphocytes, both CXCR4 and CCR5 are induced to express when they are activated or activated by various signals. CXCR4 and CCR5 sometimes aggregate into heterodimers, and the irregular combination will lead to changes in the signaling of membrane receptors and complete changes in cell physiological functions, which may produce unpredictable side effects, resulting in membrane receptors produced by them. Signaling mutagenic malignancy signaling for carcinogenesis. Therefore, in order to confirm the specific recognition ability of the three lauryl diamine derivatives in the present application to CXCR4, this experiment was carried out.

[0068] In order to confirm the binding specificity of the test compound to CXCR4 but not to CCR5, the inventors chose to use A3.01-R5T lymph...

Embodiment 1

[0071] Example 1), the Kd (dissociation constant) is selected as 2.2nM, that is, the concentration of the CCR5 2D7 antibody is 2.2nM. The reaction system is: mix 50,000 cells with 25 μl buffer + 25 μl, 2.2 nM 2D7 antibody to form a 50 μl volume of antibody receptor cell binding model, and then add from 10 -6 M concentrations of the test compounds (m2018A, m2018B, m2018C, m2018D) and the control drug (CCL4) were incubated at 4° C. for 1 hour.

[0072] b. After incubation for 1 hour, use the eluent (mixed by 0.1 μM EDTA + 1 X PBS buffer + 0.01 μM sodium azide + 1% BSA) to remove the liquid twice, each time at 1200 rpm, Centrifuge for 5 minutes and discard the supernatant. Subsequently, 1 / 1000 dilution (0.1ug / 1ml) of F(ab')goat-anti-mouse IgG (FITC-coupled) provided by Jackson ImmunoResearch was added to the above buffer, mixed evenly, light-shielded, and incubated for 30 minutes. Washing with this eluent / buffer was then repeated twice, and the cells were mixed conventionally t...

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Abstract

The invention provides an application of a lauryl diamine derivative in preparing a medicine for treating breast cancer, belonging to the field of cancer drugs. A study by that inventor found that thethree lauryl diamine derivatives represent by formulae I, II and III were capable of strongly regulating SDF-1 Possible inducible CXCR4-stimulated carcinogenesis signal, inducible modulation of SDFFrom a potent agonist to a partial or less potent agonist in physiological or pathological conditions. These three compounds can target CXCR4 specifically and kill breast cancer cells efficiently. They can be used as therapeutic agents for breast cancer and have a broad application prospect.

Description

technical field [0001] The invention relates to the field of medicines, in particular to the application of a lauryl diamine derivative in the preparation of medicines for treating breast cancer. Background technique [0002] According to the World Health Organization's International Cancer Research Center, the standardized incidence rate of female breast cancer in China was 21.6 / 100,000 in 2008. Due to the huge population base in China, the number of new breast cancer cases can reach 169,000 cases each year, accounting for the total number of breast cancer cases in the world. The number of cases is 12.25%, second only to the United States (182,000 cases), ranking second in the world. It is estimated that the incidence of female breast cancer in my country will reach 234,000 cases per year in 2030, and cause about 70,000 breast cancer deaths per year. [0003] Studies in recent years have shown that taking tamoxifen or exemestane can reduce the incidence of breast cancer in h...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4178A61P15/14A61P35/00A61P35/04
CPCA61K31/4178A61P15/14A61P35/00A61P35/04
Inventor 周志诚柴梦莹
Owner 柴梦莹
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