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Application of HDAC1 inhibitor in preparing medicine for regulating and controlling hepcidin expression

An inhibitor and drug technology, applied in drug combinations, antipyretics, anti-inflammatory agents, etc., can solve the problems of iron chelators with large side effects, aggravating the condition of patients with intolerance, etc., to reduce oxidative damage and reduce toxic side effects. , the effect of reducing serum iron and tissue iron

Inactive Publication Date: 2015-12-23
ZHEJIANG UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, some iron chelating agents currently used have severe side effects, and bloodletting therapy and liver transplantation will aggravate the deterioration of some patients who are intolerant

Method used

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  • Application of HDAC1 inhibitor in preparing medicine for regulating and controlling hepcidin expression
  • Application of HDAC1 inhibitor in preparing medicine for regulating and controlling hepcidin expression
  • Application of HDAC1 inhibitor in preparing medicine for regulating and controlling hepcidin expression

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Experimental program
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Embodiment 1

[0031] 1. Materials and Methods

[0032] 1.1 Preparation of experimental raw materials

[0033] MS-275, TSA, SAHA, MGCD0103, RGFP966, Droxinostat, TubastatinA, PCI-34051 were all purchased from selleck company. Human BMP6 was purchased from R&D Systems. Drug solution for treating Huh7 cells: HDAC inhibitors (MS-275, TSA, SAHA, MGCD0103, RGFP966, Droxinostat, TubastatinA, PCI-34051) were dissolved in DMSO to make a 10 mM drug solution.

[0034] Drug solution for intraperitoneal injection of mice: MS-275 was dissolved in a mixture of propylene glycol and saline with a volume ratio of 3:7 to make a 2.5 mg / ml drug solution.

[0035] 1.2 Cell culture

[0036] Human liver cancer cell line Huh7 (purchased from the Cell Bank of the Chinese Academy of Sciences) was prepared in DMEM high-glucose medium (GIBCO) containing 10% FBS (fetal bovine serum) at a volume concentration of 37°C, 5% CO 2 Cultivate in a saturated humidity incubator until the cells grow and merge to 70-80%, add 10...

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Abstract

The invention discloses an application of HDAC1 inhibitor in preparing medicine for regulating and controlling hepcidin expression. The medicine for regulating and controlling hepcidin expression is medicine for treating hereditary haemochromatosis, thalassemia, iron-overloaded alcoholic hepatitis, viral hepatitis and high-iron induced tumors. The HDAC1 inhibitor is one of Entecavir, trichostatin A, Vorinostat and Mocetinostat. Due to the fact that an iron chelating agent currently applied to treating hereditary haemochromatosis is large in toxic effect, many patients cannot bear blood-letting therapy and liver transplantation, MS-275 is small in toxic and side effect as clinical second-stage medicine for mainly treating cancer, research finds that secretion of liver hepcidin can be obviously promoted, serum iron and tissue iron can be lowered, oxidative damage and other complications caused by overloading of iron are reduced, and therefore the HDAC1 inhibitor can be used for preparing medicine for treating hereditary haemochromatosis, thalassemia, iron-overloaded alcoholic hepatitis, viral hepatitis and high-iron induced tumors.

Description

(1) Technical field [0001] The invention relates to the application of HDAC1 inhibitors, in particular to the application of HDAC1 inhibitors in the preparation of drugs for regulating hepcidin expression and the preparation of drugs for treating hereditary hemochromatosis. (2) Background technology [0002] Hereditary hemochromatosis (HH), also known as hemochromatosis or hemochromatosis, is a common disease of iron metabolism, with an incidence of about 1:200 among people of northern European descent. The most common form of hemochromatosis is due to an autosomal recessive mutation in the HFE gene in which cysteine ​​at position 282 is replaced by tyrosine (C282Y). Due to the HFE gene mutation, the hepcidin secreted by the liver is reduced, which in turn leads to the obstruction of iron excretion, iron overload in the body, and deposits in multiple tissues and organs such as the liver, resulting in tissue oxidative damage and organ dysfunction, including skin melanin. , l...

Claims

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Application Information

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IPC IPC(8): A61K31/4406A61K31/165A61K31/167A61K31/506A61K45/00A61P7/06A61P1/16A61P29/00A61P35/00A61P7/00A61P31/12
Inventor 王福俤闵军霞尹香菊谢恩军张英琪
Owner ZHEJIANG UNIV
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