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Use of compound in therapeutic drug for diseases related to disorder of transcription factor

A technique of compound, pharmacy, applied in the field of compound pharmacy to achieve the effect of excellent inhibitory effect, obvious drug and therapeutic use

Active Publication Date: 2012-08-15
小江生物技术有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] There is no specific drug for the treatment of cervical cancer. Now the combination drug therapy with cisplatin as the mainstay and radiation therapy is commonly used clinically. The effective rate can only reach 30-50%. Moreover, these non-specific cytotoxic drugs The adverse effect of chemical drugs on the overall health and quality of life of patients is very obvious

Method used

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  • Use of compound in therapeutic drug for diseases related to disorder of transcription factor
  • Use of compound in therapeutic drug for diseases related to disorder of transcription factor
  • Use of compound in therapeutic drug for diseases related to disorder of transcription factor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Transcription factor modulators inhibit proliferation and induce apoptosis in human cervical cancer cells:

[0063] Take the logarithmic growth phase human cervical cancer cell lines Caski, SiHa, HeLa and C4I (Caski and SiHa are HPV16-positive cell lines, HeLa and C4I are HPV18-positive cell lines) and inoculate them in 96-well plates, at 37°C, the volume fraction 5% CO 2 Incubate overnight in a saturated humidity incubator, add different concentrations of transcription factor regulator YT30, and the control group adds YT19, a compound similar in structure to YT30 but without the activity of inhibiting the interaction between transcription factors and HDACs, and continue to culture for 48 hours. Detection of proliferation and apoptosis. The CellTiter-Glo Cell Viability Fluorescent Assay Kit from Promega (Madison, WI) was used to detect cell viability, and the specific steps were referred to the manufacturer's instructions. The cell inhibition rate was calculated accor...

Embodiment 2

[0066] Calculation of IC50 of transcription factor regulators on cervical cancer cell lines and normal fibroblasts:

[0067] According to the method in Example 1, human cervical cancer cell lines Caski and HeLa in logarithmic growth phase, human fibroblast cells Fibroblast and mouse fibroblast cells L929 were obtained. Calculate the cell inhibition rate and IC50 after 48 hours and 72 hours after adding different concentrations of YT30 and the same compound YT54, as image 3 shown. The inhibitory concentration of transcription factor regulators to cervical cancer cell lines was significantly lower than that of normal fibroblasts, see Table 1.

[0068] Table 1

[0069]

[0070] Among them, mouse fibroblasts and human fibroblasts are both negative controls, and their sensitivity to the compound is much lower than that of cancer cells. The 48-hour graph of L929 in the attached figure is representative.

Embodiment 3

[0072] After being treated with YT30 and YT54 for 48 hours, human cervical cancer cells HeLa, Caski, C33A and human ovarian cancer cell line SKOV3 were observed by AnnexinV / PI staining laser confocal microscope, and early and late apoptosis rates were detected by flow cytometry. The apoptosis index (AI) was calculated from the results of AnnexinV / PI and flow cytometry (apoptosis index is the percentage of apoptotic cells in the total number of cells in the microscope / cytometer).

[0073] YT30 and YT54 act on HeLa (such as Figure 4.1 shown), Caski (as Figure 4.2 shown), C33A (such as Figure 4.3 shown) and SKOV3 (as Figure 4.4 Shown) Cells were detected by AnnexinV / PI flow cytometry after 48 hours, showing typical early and late apoptosis images.

[0074] The apoptosis index (AI) calculated according to the results of flow cytometry showed that after 48 hours of action of transcription factor regulators YT30 and YT54, HeLa (see Table 2.1), Caski (see Table 2.2), C33A (see...

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Abstract

The invention discloses the use of a compound and the drug composite of the compound in the preparation of a therapeutic drug or an ancillary therapeutic drug for diseases related to the disorder of transcription factor or ancillary factor of the transcription factor. The compound is the compound shown in the formula (I), the Z-A-Z' or the pharmacologically acceptable salt or prodrug. The use of the compound has the beneficial effects that the micromolecule compound provided by the invention is derived from pair transcription factors, such as the analysis of foxp P3 and / or myocyte enhancement factor 2 molecular structure and the interaction locus of the binding protein of the foxp P3 and / or the myocyte enhancement factor 2 molecular structure. Therefore, the micromolecule compounds can be used for adjusting the function of the related transcription factor, wherein the function comprises the interaction influencing the relevant transcription factor and the binding protein comprising various transcription factors. Due to the function adjustment of the foxp P3 and / or the myocyte enhancement factor 2, the micromolecule compounds have obvious drug and treatment uses to the malignant tumor, in particular to the treatment of the malignant tumor such as the carcinoma of uterine cervix, the breast cancer and the like, so that the animal experiment shows that the compound is extremely good in inhibition effect.

Description

technical field [0001] The invention relates to the field of compound pharmacy, in particular to the application of the compound and its pharmaceutical composition in the production of therapeutic drugs or adjuvant therapeutic drugs for diseases related to transcription factor or transcription factor cofactor imbalance. Background technique [0002] The vast majority of malignant tumors originate from the disorder of the regulatory mechanism related to cell growth, which often involves the disorder of one or more cell growth regulation links. Uncontrolled cell growth and division lead to tumors. Tumor cells are considered to be malignant tumors if they have the ability to invade surrounding tissues, and may invade other organs or reach other parts of the body from the original site through various channels. According to the origin, malignant tumors can be further divided into "carcinomas" which originate from various epithelial cells and "sarcomas" which originate from conn...

Claims

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Application Information

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IPC IPC(8): C07C233/43C07C233/25C07D213/40C07C233/54C07C233/80C07C233/44C07D213/56C07C255/60C07D213/82C07C311/21C07C311/47C07C271/58C07C237/22C07D209/08C07D401/12C07D215/38C07D207/34C07C237/10C07D235/06C07D215/54A61K31/167A61K31/444A61K31/44A61K31/277A61K31/455A61K31/18A61K31/27A61K31/404A61K31/4439A61K31/47A61K31/40A61K31/4184A61P35/00A61P35/02
Inventor 陈林陈小江陶光实夏梦盖大海
Owner 小江生物技术有限公司
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