Application of JMJD3 inhibitor GSK-J1 HCL to preparation of medicine for treating myocardial fibrosis

A myocardial fibrosis, 1. JMJD3 technology, applied in the field of preparation of drugs for the treatment of myocardial fibrosis, histone demethylase JMJD3 inhibitors, can solve problems that have not yet been seen

Pending Publication Date: 2021-04-13
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The compound GSK-J1 HCL is an effective inhibitor of histone methyltransferase JMJD3, which is mostly studied in tumors and inflammation; in related pathological processes, the removal of the methylation modification of the H3K27 site mediated by JMJD3 can affect The active state of gene expression is regulated during the occurrence and development of the disease. The relevant experimental results also reveal that GSK-J1 HCL participates in the improvement of collagen deposition by inhibiting JMJD3, and regulates the effect of myocardial fibrosis. Reports on the effects of chemotherapeutics

Method used

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  • Application of JMJD3 inhibitor GSK-J1 HCL to preparation of medicine for treating myocardial fibrosis
  • Application of JMJD3 inhibitor GSK-J1 HCL to preparation of medicine for treating myocardial fibrosis
  • Application of JMJD3 inhibitor GSK-J1 HCL to preparation of medicine for treating myocardial fibrosis

Examples

Experimental program
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Effect test

Embodiment 1

[0023] Example 1 GSK-J1 HCL increases EF% and FS% values ​​after myocardial infarction, reduces collagen deposition in tissues, and inhibits expression of fibrosis effector proteins in cardiac tissues Animal experiments

[0024] Male C57BL / 6J mice weighing 25-30 g were fixed in supine position after gas anesthesia with isoflurane, and the chest skin was prepared. A thoracotomy was performed in the third and fourth intercostal spaces of the left chest cavity, and the left anterior descending coronary artery was permanently ligated between the left atrial appendage and the conus pulmonary artery with a 7-0 suture needle at about 1 mm from the root of the aorta. The whitening of the myocardium to the blood supply area is the criterion for the success of the model. The thorax was closed quickly, the skin was sutured after being cleaned with sterile normal saline, and the mice were kept warm and fed water and standard feed in separate cages after they woke up. In the sham operatio...

Embodiment 2

[0026] Example 2 GSK-J1 HCL reduces Ang II-induced collagen content and effector protein levels in NRCFs cells

[0027] Rat suckling mouse primary cardiac fibroblasts (NRCFs) were cultured in DMEM medium containing 10% fetal calf serum, placed in a 5% CO2 incubator at 37°C, when the cell confluence reached 80-90% Subculture; cells were planted in 24-well plates, and normal control group (Control, no drug intervention, without Ang II), model group (Model, no drug intervention, Ang II stimulation for 48h), GSK-J1 HCL group (GSK-J1 HCL, 20μM, pretreated 4h in advance and then stimulated with Ang II); the results of immunofluorescence showed that GSK-J1 HCL could effectively reduce the collagen content in primary cardiac fibroblasts; After being induced by Ang II for 48 hours, the cells were lysed to extract protein; Western-Blotting method was used to detect myocardial fibrosis effector proteins CTGF and FN, and the results showed that GSK-J1 HCL could significantly reduce the ex...

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Abstract

The invention belongs to the field of pharmacy, and relates to a new application of a compound GSK-J1 HCL to pharmacy, in particular to an application of a histone demethylase JMJD3 inhibitor GSK-J1 HCL to preparation of a medicine for treating myocardial fibrosis. Through an established myocardial fibrosis model caused by a mouse left coronary artery ligation operation and an Ang II induced NRCFs in-vitro myocardial fibrosis model experiment, a result shows that the GSK-J1 HCL has a regulation and control effect on myocardial fibrosis by inhibiting expression of JMJD3 to reduce collagen content and reducing expression of fibrosis related protein. The compound GSK-J1 HCL (C22H23N5O2.HCL) and the related inhibitor thereof can be used for preparing the medicine for preventing and treating myocardial fibrosis diseases.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to a new application of compound GSK-J1 HCL in pharmacy, in particular to the application of GSK-J1 HCL, an inhibitor of histone demethylase JMJD3, in the preparation of drugs for treating myocardial fibrosis. Background technique [0002] The prior art discloses that myocardial infarction (myocardial infarction, MI) is myocardial necrosis caused by severe and persistent ischemia of the corresponding myocardium due to a sharp reduction or interruption of coronary blood supply, which can lead to ventricular remodeling and can gradually progress Heart failure is a serious threat to human health and life. Studies have shown that myocardial fibrosis (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. D...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/55A61P9/04A61P9/10
CPCA61K31/55A61P9/04A61P9/10
Inventor 刘新华朱依谆龙芬
Owner FUDAN UNIV
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