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Pharmaceutical uses of NBC1 N-cyano amide sulfide inhibitor S0859

A sulfur amide and inhibitor technology, applied in the direction of amide active ingredients, drug combinations, cardiovascular system diseases, etc., to achieve the effects of inhibiting ventricular remodeling, delaying ventricular remodeling, and inhibiting intracellular calcium overload

Inactive Publication Date: 2019-02-01
NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Whether S0859 plays a role in myocardial infarction and whether it can regulate intracellular sodium and calcium ion balance has not yet been reported

Method used

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  • Pharmaceutical uses of NBC1 N-cyano amide sulfide inhibitor S0859
  • Pharmaceutical uses of NBC1 N-cyano amide sulfide inhibitor S0859
  • Pharmaceutical uses of NBC1 N-cyano amide sulfide inhibitor S0859

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Experimental program
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Embodiment Construction

[0016] The present invention will be described in detail below with specific embodiments in conjunction with the accompanying drawings.

[0017] 1. Purpose of the experiment

[0018] The effect of overexpression of NBC1 on cardiac function, hemodynamics and infarct size after myocardial infarction was observed in vivo; the changes of calcium ion kinetics in adult rat cardiomyocytes were observed in vitro.

[0019] 2. Experimental materials

[0020] NBC1 N-cyanosulfuramide inhibitor S0859, purchased from Sigma-Aldrich, USA, is a selective high-affinity NBC1 inhibitor, but it has no effect on sodium-hydrogen ion exchangers.

[0021] 3. Experimental animals

[0022] Cardiac-specific NBC1 overexpressing mice. The inventors made an open reading frame fragment containing human NBC1 (SLC4A4) flanked by sal I, which was inserted into the sali position of the α-myhc clone 26 vector, linked to the mouse α-myosin heavy chain promoter , and the entire 9.3 kb fragment including the α-M...

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PUM

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Abstract

The present invention relates to pharmaceutical uses of a Na<+>-coupled HCO3< > transporter (NBC1) N-cyano amide sulfide inhibitor S0859, and provides uses of a Na<+>-coupled HCO3< > transporter (NBC1) N-cyano amide sulfide inhibitor S0859 in preparation of heart failure treating drugs. According to the present invention, the results prove that the inhibitor S0859 can regulate the intracellular calcium ion homeostasis after myocardial infarction, improve ventricular remodeling, and inhibit intracellular calcium overload so as to inhibit ventricular remodeling, such that the invention can provide a new heart failure treating drug so as to effectively delay heart failure and ventricular remodeling caused by myocardial infarction.

Description

technical field [0001] The present invention relates to the new use of S0859, an N-cyanosulfuramide inhibitor of sodium bicarbonate ion transporter (NBC1), in particular to the pharmaceutical use of S0859. Background technique [0002] Myocardial infarction is the most common cause of heart failure and ultimately death. After myocardial infarction, the nerves and body fluids in the body undergo a series of changes to maintain a new homeostasis in the cells. These changes include changes in the use of energy by the heart and changes in the acid-base balance in cardiomyocytes. After cell hypoxia, the glycolytic function in the body increases, the acidic metabolites in the cell accumulate, and the pH decreases. + or transport HCO 3 - Enter the cell, thereby adjusting the pH value of the cell. Studies have shown that the expression of myocardial NBC1 increases in heart failure, suggesting that cardiomyocytes excrete H in pathological conditions. + Enhanced capabilities. N...

Claims

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Application Information

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IPC IPC(8): A61K31/18A61P9/06A61P9/10
CPCA61K31/18A61P9/06A61P9/10
Inventor 廖禹林陈震寰林海若宾建平
Owner NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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