Application of compound EPZ5676 and related inhibitor thereof in preparing drug for preventing and treating myocardial fibrosis diseases

A technology of EPZ5676 and myocardial fibrosis, which is applied in the field of compound EPZ567 and its related inhibitors to prepare drugs for treating myocardial fibrosis, and can solve the problems such as the therapeutic effect of EPZ5676 on myocardial fibrosis that has not been seen yet.

Active Publication Date: 2018-11-02
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But so far, there is no report that EPZ5676 has a therapeutic effect on myocardial fibrosis

Method used

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  • Application of compound EPZ5676 and related inhibitor thereof in preparing drug for preventing and treating myocardial fibrosis diseases
  • Application of compound EPZ5676 and related inhibitor thereof in preparing drug for preventing and treating myocardial fibrosis diseases
  • Application of compound EPZ5676 and related inhibitor thereof in preparing drug for preventing and treating myocardial fibrosis diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] This example shows that EPZ5676 can significantly increase EF% and FS% values ​​after myocardial infarction, reduce collagen deposition in tissue, and inhibit the expression of fibrosis effector proteins in cardiac tissue.

[0023] In the experiment, a male C57BL / 6J mouse weighing 25-30 g was fixed supine after isoflurane gas anesthesia, and the chest was skin-prepared; the chest was opened in the third and fourth intercostal spaces of the left chest, and sutured with 7-0 suture The needle was placed between the left atrial appendage and the conus pulmonary artery, and the left anterior descending coronary artery was permanently ligated about 1mm from the root of the aorta. The successful criterion of the model was to observe the myocardium in the blood supply area; After waking up, the rats were fed with water and standard feed in separate cages; in the sham operation group, the operation was the same except that the coronary artery was not ligated; EPZ5676 was dissolve...

Embodiment 2

[0026] This example shows that EPZ5676 reduces the collagen content and effector protein levels of aCFs cells induced by TGF-β;

[0027] Rat primary cardiac fibroblasts were cultured in DMEM medium containing 10% fetal bovine serum, cultured in a 5% CO2 incubator at 37°C, and passaged when the cell confluence reached 80-90%. In a 24-well plate, set up the normal control group (Control, no drug intervention, no TGF-β), model group (Model, no drug intervention, TGF-β stimulation 48h), EPZ5676 group (EPZ5676, 25μM, pre-added 4h in advance stimulated with TGF-β); the results of immunofluorescence showed that EPZ5676 can effectively reduce the collagen content and the level of effector proteins in primary cardiac fibroblasts (such as Figure 5 , Figure 6 shown); the cells were planted in a 6-well plate, each experimental control group was induced by TGF-β for 48 hours, and then the cells were lysed to collect proteins. The Western-Blotting method was used to detect the cardiac fi...

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PUM

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Abstract

The invention belongs to the field of pharmacy and relates to novel application of a compound EPZ5676 in pharmacy, in particular to application of a compound EPZ567 (C30H42N8O3) and a related inhibitor thereof in preparing a drug for preventing and treating myocardial fibrosis diseases. According to the application, a model experiment for myocardial fibrosis caused by left coronary artery ligationoperation of mice and a TGF-beta induced aCFs in vitro myocardial fibrosis model experiment are established; the results show that the content of collagen is reduced by inhibiting the expression of DOT1L through the EPZ5676, and the regulation action of expression of fibrosis-related protein on myocardial fibrosis is reduced; the compound EPZ5676 inhibits a fibrosis effect of primary myocardial fibroblasts. The compound EPZ5676 and the related inhibitor thereof can be used for preparing a drug for preventing and treating the myocardial fibrosis diseases.

Description

technical field [0001] The invention belongs to the field of pharmacy and relates to the new application of compound EPZ5676 in pharmacy, in particular to compound EPZ567 (C 30 h 42 N 8 o 3 ) and related inhibitors thereof in the preparation of medicines for the treatment of myocardial fibrosis. Background technique [0002] The prior art discloses that myocardial infarction (myocardial infarction, MI) is an ischemic cardiomyopathy caused by obstruction of the coronary artery or its branches, which can lead to ventricular remodeling, and can gradually progress to heart failure, seriously threatening human health and life. Myocardial fibrosis (MF) is a common pathological change in the development of various heart diseases to a certain stage. It is one of the most characteristic structural changes and one of the main manifestations of ventricular remodeling after MI. It can promote myocardial contraction. and diastolic dysfunction. Studies have shown that long-term acti...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/497A61P9/00
CPCA61K31/497
Inventor 朱依谆刘新华刘斯语
Owner FUDAN UNIV
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