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Caspase-1 inhibitor targeting liver and application thereof

A pre-s1, inhibitor technology, applied in biomedicine, enzyme inhibitor and in the field of medicine, can solve problems such as difficulty in terminating chronic hepatitis B, and achieve the effect of reducing production, reducing internal environment disturbance and immune deficiency

Active Publication Date: 2014-03-19
ARMY MEDICAL UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, studies have found that even if the virus replication is effectively inhibited, it is difficult to stop the malignant course of chronic hepatitis B from progressing to cirrhosis / liver failure, which is precisely the main harm of chronic hepatitis B
At present, there are no effective therapeutic strategies and drugs that can block the malignant progression of chronic hepatitis

Method used

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  • Caspase-1 inhibitor targeting liver and application thereof
  • Caspase-1 inhibitor targeting liver and application thereof
  • Caspase-1 inhibitor targeting liver and application thereof

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Embodiment Construction

[0018] Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. The experimental methods for which specific conditions are not indicated in the preferred embodiments are usually in accordance with conventional conditions, or in accordance with the conditions suggested by the manufacturer.

[0019] 1. Preparation of liver-targeted caspase-1 inhibitors

[0020] Design and entrust Sangon Bioengineering (Shanghai) Co., Ltd. to synthesize a liver-targeting caspase-1 inhibitor whose amino acid sequence is shown in SEQ ID No.1. In the sequence shown in SEQ ID No.1, amino acids 1-50 are derived from the amino acid sequence 1-50 of the Pre-S1 protein of hepatitis B virus strain FMC#97, and amino acids 51-53 are flexible Linker, the 54th-65th amino acid is a trimolecular polymer of YVAD (Tyr-Val-Ala-Asp) tetrapeptide, the 66th-68th amino acid is a flexible linker, and the 69th-77th amino acid is VAD (Val-Ala-As...

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Abstract

The invention discloses a caspase-1 inhibitor targeting liver. The caspase-1 inhibitor is formed by connection of human hepatitis B virus Pre-S1 peptide and caspase-1 inhibitor through a flexible connector, wherein the Pre-S1 peptide consists of amino acids from first to fiftieth of the Pre-S1 protein; and the caspase-1 inhibitor is formed by connection of trimolecular polymer of YVAD tetrapeptide and trimolecular polymer of VAD tripeptide. According to the inhibitor, the caspase-1 inhibitor is specifically targeted to a liver cell by utilizing the carrier Pre-S1 peptide which specifically targets liver, so that intrahepatic persistent chronic inflammation caused by endogenous danger signals released by injured liver cells can be blocked by terminating caspase-1 activation in the liver cell, sequential spinal cord injury of the liver cell can be blocked, body adverse response which is possibly caused by spread inhibition of caspase-1 can be reduced, and the liver cell can be specifically and effectively protected. The caspase-1 inhibitor can be used for preparing a medicament for treating intrahepatic chronic inflammation caused by endogenous danger signals released by injured liver cells.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to an enzyme inhibitor and its application in the field of medicine. Background technique [0002] Chronic liver injury mainly caused by chronic hepatitis is a major health problem in my country, and it is also one of the main causes of human death announced by the World Health Organization. Once chronic liver inflammation starts, it is difficult to stop, and further causes liver cirrhosis, liver failure, and liver cancer, which is called the "trilogy of chronic liver disease"; trauma". [0003] Previous studies have believed that the activity of the virus in the liver is an important reason for the persistence of intrahepatic inflammation, so antiviral therapy is currently the most commonly used method for the treatment of chronic hepatitis B. However, studies have found that even if the virus replication is effectively inhibited, it is difficult to stop the malignant course of chronic h...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K19/00A61K38/16A61K47/48A61P1/16A61P29/00
Inventor 王靖雪吴玉章刘钱刘宏利
Owner ARMY MEDICAL UNIV
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