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Application of ferroptosis inhibitor in preparation of medicine for treating iron overload disease

A technology for inhibitors and iron overload, applied in metabolic diseases, blood diseases, drug combinations, etc., can solve problems such as iron overload diseases that have not been used or reported

Active Publication Date: 2019-04-23
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Currently known ferroptosis inhibitors include Ferrostatin-1, tocopherol, β-mercaptoethanol, etc., none of which have been used or reported to treat iron overload diseases such as hereditary hemochromatosis

Method used

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  • Application of ferroptosis inhibitor in preparation of medicine for treating iron overload disease
  • Application of ferroptosis inhibitor in preparation of medicine for treating iron overload disease
  • Application of ferroptosis inhibitor in preparation of medicine for treating iron overload disease

Examples

Experimental program
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Embodiment 1

[0025] 1. Materials and Methods

[0026] 1.1 Preparation of experimental raw materials

[0027] Compound monomers Ferrostatin-1, DFO, Z-VAD-FMK, Necrostatin-1 and ferric citrate were purchased from SIGMA Company. Ferrostatin-1, DFO, Z-VAD-FMK, and Necrostatin-1 were dissolved in sterile dimethyl sulfoxide DMSO, ferric citrate was dissolved in phosphate buffer, and prepared to the desired concentration.

[0028] 1.2 Mouse liver primary cells

[0029] Primary mouse liver cells were obtained from C57BL / 6 mouse liver by collagenase type II buffered perfusion. Culture conditions: DMEM high-glucose medium (GIBCO) containing 10% FBS (GIBCO), 37°C, 5% CO2 saturated humidity incubator. After the cells adhered to the wall, phosphate buffered saline (PBS), ferric citrate (100 μM, final concentration, the same below), ferric citrate (100 μM) + apoptosis inhibitor (10 μg / mL), citric acid Iron (100 μM) + necrosis inhibitor (10 μg / mL), ferric citrate (100 μM) + Ferrostatin-1 (2 μM). Aft...

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Abstract

The invention discloses applications of a ferroptosis inhibitor in preparing medicines for treating iron overload diseases. The ferroptosis inhibitor is Ferrostatin-1. With the adoption of the applications, a theoretical foundation is provided for the treatment on the iron overload diseases taking ferroptosis as the target spot, especially, a foundation is provided for the research and development of drugs for treating the genetic hemochromatosis.

Description

technical field [0001] The invention relates to the application of Ferrostatin-1, an inhibitor of ferroptosis, in the treatment of iron overload diseases. Background technique [0002] Ferroptosis is an iron-dependent cell death pathway, which is different from other death pathways such as apoptosis, necrosis, and autophagy. Ferroptosis is manifested as an increase in the level of cellular lipid peroxidation and the expression of the marker gene Ptgs2, which can be specifically inhibited by iron ion chelators. [0003] Ferrostatin-1 is currently recognized as a ferroptosis inhibitor. As a compound containing N-cyclohexyl, Ferrostatin-1 has a high affinity with the cell membrane phospholipid bilayer, and can effectively remove cell membrane lipid peroxidation. In vitro experiments, Ferrostatin-1 acts on cancer cells to inhibit the accumulation of Erastin-induced cytoplasmic and lipid ROS, thereby inhibiting ferroptosis. Ferrostatin-1 inhibits glutamate-induced neuronal fer...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/245A61P7/00A61P3/12
CPCA61K31/245
Inventor 王福俤王浩闵军霞
Owner ZHEJIANG UNIV
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