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Application of AR inhibitor and/or HIF-1[alpha] inhibitor in preparation of medicine

A technology of HIF-1 and α inhibitors, applied in drug combination, compound screening, antipyretic drugs, etc., can solve the problems of not improving the outcome of critically ill patients, and achieve the goal of improving clinical curative effect, significant curative effect, and maintaining lung function Effect

Active Publication Date: 2021-04-02
SUZHOU MOLECULAR INTERSECTION BIOMEDICAL CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At the same time, existing research disclosed (Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentretrial, Vol 395 May 16, 2020, the lancet, ), Remdesivir is used in clinical trials for severe COVID-19 cases The failure of (NCT04257656) also shows that antiviral infection alone cannot improve the outcome of severe patients, and the main cause of severe viral pneumonia is hypoxemia

Method used

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  • Application of AR inhibitor and/or HIF-1[alpha] inhibitor in preparation of medicine
  • Application of AR inhibitor and/or HIF-1[alpha] inhibitor in preparation of medicine
  • Application of AR inhibitor and/or HIF-1[alpha] inhibitor in preparation of medicine

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Embodiment 1

[0053] Using bioinformatics Seurat 3.0 and Single R software to analyze the single-cell transcriptome sequencing data of patients with severe COVID-19 and uninfected patients, it was found that the expression level of HIF-1α in lung fibroblasts of infected patients was much higher than that of uninfected patients Expression levels of HIF-1α in lung fibroblasts.

[0054] Single-cell transcriptome sequencing data of patients with novel coronavirus pneumonia: GSM4516279, GSM4516280, GSM4516281, GSM4516282 Data website: https: / / www.ncbi.nlm.nih.gov / geo.

[0055] Single-cell transcriptome sequencing data of uninfected patients with novel coronavirus pneumonia: E-MTAB-6149, E-MTAB-6653 data website: https: / / www.ebi.ac.uk / arrayexpress.

[0056] Analysis results such as figure 1 As shown, it shows that HIF-1α is highly expressed in lung fibroblasts of patients with severe new coronary pneumonia.

Embodiment 2

[0058] The combination of HIF-1α and AR in the promoter regions of related genes (IL6, MMP2, MMP13, ADAMTS4, ELN, VCAN, COL3A1, VEGFA) was analyzed by TFmapper and UCSC Genome Browser bioinformatics analysis website tools. The results of bioinformatics analysis showed that HIF-1α and AR could bind to the promoter regions of related genes (IL6, MMP2, MMP13, ADAMTS4, ELN, VCAN, COL3A1, VEGFA), thereby affecting the transcription of related genes.

Embodiment 3

[0060] Figure 3A The expression levels of ACE2 and TMPRSS2 genes were analyzed by bioinformatics Seurat 3.0 and Single R software to analyze the single-cell transcriptome sequencing data of severe patients with new coronary pneumonia and the single-cell transcriptome sequencing data of uninfected patients with new coronary pneumonia.

[0061] Single-cell transcriptome sequencing data of patients with novel coronavirus pneumonia: GSM4516279, GSM4516280, GSM4516281, GSM4516282 Data website: https: / / www.ncbi.nlm.nih.gov / geo.

[0062] Single-cell transcriptome sequencing data of uninfected patients with novel coronavirus pneumonia: E-MTAB-6149, E-MTAB-6653 data website: https: / / www.ebi.ac.uk / arrayexpress.

[0063] Analysis results such as Figure 3A As shown, the experimental results showed that the expression levels of ACE2 and TMPRSS2 genes in lung fibroblasts of patients with severe new coronary pneumonia and those without new coronary pneumonia were low and there was no sign...

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Abstract

The invention discloses application of an HIF-1[alpha] inhibitor or an AR inhibitor or a combination of the HIF-1[alpha] inhibitor and the AR inhibitor in inhibiting inflammatory factor storm and preventing or treating viral pneumonia. According to the application, the HIF-1[alpha] inhibitor and the AR inhibitor are found to prevent transcription of inflammatory factor storm related genes (IL6, MMP2, MMP13, ADAMTS4, ELN, VCAN, COL3A1 and VEGFA) in a hypoxic environment in fibroblasts by effectively inhibiting mutual binding of HIF-1[alpha] and AR, so that the expression quantity of the relatedgenes is reduced, and activation of lung fibroblasts in the hypoxic environment is inhibited. Activation of the lung fibroblasts is inhibited, so that lung functions of acute respiratory distress syndrome (ARDS) patients with severe respiratory tract infection can be maintained, and clinical curative effects are improved; and moreover, the HIF-1[alpha] inhibitor and the AR inhibitor have the advantages of being low in cost, small in toxic and side effect and remarkable in curative effect, and a new strategy is provided for treatment of the viral pneumonia.

Description

technical field [0001] The invention belongs to the technical field of viral pneumonia treatment, and specifically relates to the application of AR inhibitors and / or HIF-1α inhibitors in the preparation of drugs for inhibiting inflammatory factor storm, prevention or treatment of viral pneumonia. Background technique [0002] Severe respiratory infections can lead to acute respiratory distress syndrome (ARDS). There are currently no effective drug treatments that have been shown to improve outcomes in patients with ARDS. While the host's inflammatory response limits the pathogen's spread and eventually clears it, immunopathology is one of the main causes of tissue damage and ARDS. In addition, lung fibroblasts play an important role in viral pneumonia. Respiratory viral infection induces distinct fibroblast activation states, including extracellular matrix (ECM) synthesis, injury response, and interferon-responsive states. Overactivity of injury-responsive lung fibroblast...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K45/06A61P11/00A61P29/00A61P31/14G01N33/74G01N33/68A61P31/16
CPCA61K45/00A61K45/06A61P11/00A61P29/00A61P31/14G01N33/743G01N33/6893A61P31/16G01N2333/70567G01N2333/723G01N2500/02G01N2800/7095G01N2800/12A61P37/06A61K31/5025A61K31/198A61K31/4155A61K31/18A61K31/4439A61K31/58A61K31/245A61K31/4166
Inventor 周翊峰郭强张征郭宾宾吴思奇
Owner SUZHOU MOLECULAR INTERSECTION BIOMEDICAL CO LTD
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