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Pharmaceutical application of beta-catenin specific inhibitor

A catenin, specific technology, applied in the field of medicine

Active Publication Date: 2022-03-25
ZHONGSHAN HOSPITAL FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] β-catenin-IN-2 is an effective β-catenin-specific inhibitor, and its target is mainly to inhibit the activation of β-catenin. This compound was first reported in US20150374662A1 for the treatment of colon cancer, 2021 Reported use in stomach cancer research, but no use for heart disease

Method used

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  • Pharmaceutical application of beta-catenin specific inhibitor
  • Pharmaceutical application of beta-catenin specific inhibitor
  • Pharmaceutical application of beta-catenin specific inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1 Comparison of heart size in mice with dilated cardiomyopathy before and after administration

[0023] This experiment is a comparison experiment of heart size before and after administration of cardiomyopathy mice. figure 1 A mouse model of right ventricle-dominant dilated cardiomyopathy caused by DSC2 deletion. The size of the mouse heart was detected by echocardiography, and the mice were given drug intervention when the cardiac cavity of the mouse became larger. figure 1 A represents cardiomyopathy mice-placebo group; figure 1 B shows the β-catenin-IN-2 administration group of cardiomyopathy mice. Through multiple experiments, it was found that the mice with dilated cardiomyopathy showed significantly enlarged hearts after intraperitoneal injection of placebo in the control group ( figure 1 A), while the β-catenin-IN-2 administration group did not change the heart ( figure 1 B).

Embodiment 2

[0024] Example 2 Comparison of myocardial apoptosis before and after administration of cardiomyopathy mice

[0025] This experiment is a comparison of myocardial apoptosis before and after administration of cardiomyopathy mice. figure 2 A mouse model of right ventricle-dominant dilated cardiomyopathy caused by DSC2 deletion. The apoptosis-related detection of mouse cardiomyocytes was performed by Tunel, and the mice were subjected to drug intervention when the cardiac cavity of the mice became larger. in figure 2 A (WT group), figure 2 B (WT+IN-2 group), figure 2 C (KO group), figure 2 The D(KO+IN-2) group represents the normal control mice-placebo group, the normal control mice-administration group, the cardiomyopathy mice-placebo group, and the cardiomyopathy mice-administration group, respectively. Through multiple experiments, it was found that the cardiomyopathy mice showed a significant increase in myocardial apoptosis after intraperitoneal injection of placebo...

Embodiment 3

[0026] Example 3 Comparison of myocardial contractility before and after administration of cardiomyopathy mice

[0027] This experiment is a comparison of myocardial contractility before and after administration of cardiomyopathy mice. image 3 The contractility of cardiomyocytes in mice with dilated cardiomyopathy caused by DSC2 deletion. image 3 A, 3B, and 3C represent the cell length, maximal systolic rate, and maximal diastolic rate when a single cardiomyocyte contracts; and in each figure, the WT group, KO group, and KO+IN-2 group represent normal mice-placebo group, Cardiomyopathy mice-placebo group and cardiomyopathy mice-administration group. Through the single-contraction experiment of isolated KO mouse cardiomyocytes, it was found that after intraperitoneal injection of placebo, cardiomyocytes in cardiomyopathy mice showed a decrease in cardiomyocyte contractility, but in cardiomyopathy mice intraperitoneal injection of β-catenin-IN- After 2, the contractility of ...

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PUM

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Abstract

The invention provides application of a beta-catenin specific inhibitor in preparation of a medicine for treating heart diseases. The beta-catenin specific inhibitor has the effect of treating the heart diseases such as dilated heart disease and myocardial fibrosis. Great clinical significance is realized on further development of related treatment medicines.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the pharmaceutical use of a beta-catenin specific inhibitor. Background technique [0002] Dilated cardiomyopathy (DCM), the third most common cause of heart failure, is a severe cardiac heterogeneous pathological disease characterized by ventricular dilatation with systolic and diastolic phases. disfunction. Myocardial fibrosis is a pathological entity of extracellular matrix remodeling that often results in increased myocardial stiffness, with both reactive (interstitial and perivascular) and reparative (replacement) fibrosis in DCM, suggesting that Inflammation and microvascular damage are involved in the disease process. In patients with DCM, myocardial fibrosis is associated with poor prognosis and impaired response to therapeutic interventions. It is suggested that anti-fibrotic therapy may help to improve the cardiac function of the diseased heart. Fibroblasts are con...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/404A61P9/00A61P9/04A61P9/06
CPCA61K31/404A61P9/00A61P9/04A61P9/06
Inventor 龚惠戴宇翔葛均波邹妍黄晨兴
Owner ZHONGSHAN HOSPITAL FUDAN UNIV
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