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Application of Derivatives of 4n Heterocyclic Compounds in the Preparation of Medicines for Treating Autoimmune Diseases

A technology for autoimmune diseases and heterocyclic compounds, which can be used in drug combinations, skin diseases, bone diseases, etc., can solve the problems of weakening clinical symptoms, poor selectivity, and reducing the differentiation ability of Th17 cells, and achieve the effect of inhibiting the activity of Th17 cells

Active Publication Date: 2020-10-30
SUN YAT SEN UNIV
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  • Abstract
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  • Claims
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Problems solved by technology

At present, the natural ligand of RORγt has not been found, but two recent studies found that the synthetic molecule digoxin and its derivatives (Huh et al., 20011; Fujita-Sato et al., 2011) and SR1001 (Solt et al .,2011) can specifically bind to the ligand domain of RORγt, inhibit the function of RORγt and reduce the differentiation ability of Th17 cells, and attenuate the clinical symptoms of mouse autoimmune disease EAE
However, digoxin and its derivatives are highly toxic (Paula et al., 2005); although SR1001 molecule can effectively inhibit the differentiation of Th17 cells in vitro, it can be administered at high concentrations (40 mg / kg ), can only slightly alleviate the clinical symptoms of EAE
In addition, SR1001 can interact with other RORs with poor selectivity (Solt et al.,2011)
On the one hand, these studies show that inhibiting the function of RORγt to treat autoimmune diseases is a feasible solution, but an ideal target drug has not yet been found

Method used

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  • Application of Derivatives of 4n Heterocyclic Compounds in the Preparation of Medicines for Treating Autoimmune Diseases
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  • Application of Derivatives of 4n Heterocyclic Compounds in the Preparation of Medicines for Treating Autoimmune Diseases

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[0022] In order to better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments and accompanying drawings.

[0023] Reagent source

[0024] The cell line Jurkat was preserved in our laboratory; the DH5α bacterial strain was donated by Professor Ma Runlin, Institute of Genetics, Chinese Academy of Sciences, Beijing; the restriction endonuclease was purchased from Fermentas Company of the United States; the DNA ligase was purchased from NEB Company of the United States; the reporter gene sequence IRES-GFP was the inventor Self-preservation (other existing reporter gene sequences can also be used); reporter plasmid pGL4.31[luc2P / GAL4UAS / Hygro] and pBIND plasmid were purchased from Promega Company in the United States; DMEM medium and RPMI1640 medium and acetone for culturing cells Sodium phosphate, glutamine, β-mercaptoethanol, non-essential amino acids, a...

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Abstract

The invention discloses an application of a derivative of a 4N heterocyclic compound in preparation of drugs for treating autoimmune diseases. A study finds that the derivative of the 4N heterocyclic compound is capable of inhibiting Th17 cell differentiation and formation as an inhibitor of Th17 cell activity.

Description

technical field [0001] The present invention relates to a new application of derivatives of 4N heterocyclic compounds, in particular to the application of derivatives of 4N heterocyclic compounds in the preparation of medicines for treating autoimmune diseases. Background technique [0002] About 5% of the population suffers from autoimmune diseases, and more than 70 human diseases are related to autoimmune disorders (Goodnow et al., 2005). At present, the treatment of autoimmune diseases mainly relies on some non-selective immunosuppressants, which have limited curative effect and large side effects. There is no very effective drug for the treatment of autoimmune diseases in clinical practice. Therefore, there is an urgent need to develop a new type of autoimmune drug with high efficacy and low side effects. [0003] Recent studies have shown that a new T cell subset, Th17 cells, is closely related to the occurrence of human autoimmune diseases and related animal models (;...

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/519A61P37/06A61P17/06A61P17/00A61P19/02A61P29/00A61P11/06A61P1/00
CPCA61K31/519
Inventor 黄朝峰何细新柏川陈焕鹏周晓庆
Owner SUN YAT SEN UNIV
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