Application of Gli1 inhibitor to preparation of medicines for treating cholestatic liver fibrosis and liver cirrhosis

A technology for liver fibrosis and cholestasis, applied in the fields of molecular biology and liver disease prevention and treatment

Pending Publication Date: 2021-03-09
SHUGUANG HOSPITAL AFFILIATED WITH SHANGHAI UNIV OF T C M
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no report about the application of Gli1 inhibitors in the preparation of drugs for the treatment of cholestatic liver fibrosis and liver cirrhosis.

Method used

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  • Application of Gli1 inhibitor to preparation of medicines for treating cholestatic liver fibrosis and liver cirrhosis
  • Application of Gli1 inhibitor to preparation of medicines for treating cholestatic liver fibrosis and liver cirrhosis
  • Application of Gli1 inhibitor to preparation of medicines for treating cholestatic liver fibrosis and liver cirrhosis

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Experimental program
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Embodiment 1

[0025] 1. Materials and methods

[0026] 1.1 Animals

[0027] Male SD rats aged 6-8 weeks, weighing 160-180g, were purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd., SPF grade; Mdr2 - / - Knockout and Mdr2 + / +Wild-type mice were purchased from Shanghai Southern Model Organism Research Center, SPF grade, and were raised in the Animal Experiment Center of Shanghai University of Traditional Chinese Medicine, with constant temperature and humidity, 12 hours of day and night, and free diet. All animal experiments were approved by the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (NO.201608001).

[0028] 1.2 Small molecule inhibitors

[0029] GANT61: inhibitor of Gli1; ​​purchased from Sellek Company.

[0030] 1.3 Animal model preparation and administration

[0031] (1) Bile duct ligation model of biliary liver fibrosis: SD rats were randomly divided into a sham operation group (Sham group) and a bile duct ligation mode...

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PUM

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Abstract

The invention relates to a biomedical application of GANT61 as a Gli1 gene expression inhibitor. The invention also provides a biomedical application of the GANT61 to preparation of medicines for treating cholestatic liver fibrosis and liver cirrhosis. The invention also provides a medicine preparation. The medicine preparation comprises an active component GANT61 or pharmaceutical salt thereof, and a pharmaceutically acceptable carrier or excipient. The medicine preparation is made into a pharmaceutically acceptable dosage form. The invention provides a novel targeting gene for treating the cholestatic liver fibrosis and the liver cirrhosis, the expression of Gli1 in the liver with the cholestatic liver fibrosis and the liver cirrhosis is increased, a bile duct reaction can be remarkablyinhibited by inhibiting the expression of the Gli1, and then the progress of the cholestatic liver fibrosis and the liver cirrhosis is inhibited; and the gene is used as a target, innovative medicinesfor treating the cholestatic liver fibrosis and the liver cirrhosis by aiming at the gene and related molecules thereof can be designed.

Description

technical field [0001] The invention belongs to the fields of molecular biology and liver disease prevention and treatment, and relates to a target gene, in particular to a target gene for treating cholestatic liver fibrosis and liver cirrhosis. Background technique [0002] Cholestatic cirrhosis is liver cirrhosis caused by biliary obstruction and cholestasis, divided into primary cirrhosis and secondary biliary cirrhosis, which is caused by long-term obstruction of extrahepatic bile ducts. It is generally believed that primary biliary cirrhosis is an autoimmune disease, clinically slow and progressive, often accompanied by other autoimmune diseases, such as Sjogren's syndrome, systemic lupus erythematosus, rheumatoid arthritis and chronic lymphatic thyroiditis. The Gli family is a group of transcription factor proteins with zinc finger domains. They bind DNA through zinc finger motifs. They were named after their abnormally high expression was first discovered in malignan...

Claims

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Application Information

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IPC IPC(8): A61K31/506A61P1/16
CPCA61K31/506A61P1/16
Inventor 陈佳美刘平胡永红方静周群刘伟付亚东周小茜慕永平陈高峰
Owner SHUGUANG HOSPITAL AFFILIATED WITH SHANGHAI UNIV OF T C M
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