Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Application of C188-9, Venetoclax and Bumetanide in drugs for fibrotic diseases

A fibrotic disease, fibrosis technology, applied in sexual diseases, blood diseases, bone diseases, etc., can solve problems such as affecting collagen synthesis and increasing the stability of collagen mRNA

Inactive Publication Date: 2020-11-24
TIANJIN MEDICAL UNIV
View PDF3 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] There are very few studies on the post-transcriptional regulation of collagen. Currently, only reports indicate that LARP6 can act as an RNA-binding protein to increase the stability of collagen mRNA, thereby affecting collagen synthesis.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Application of C188-9, Venetoclax and Bumetanide in drugs for fibrotic diseases
  • Application of C188-9, Venetoclax and Bumetanide in drugs for fibrotic diseases
  • Application of C188-9, Venetoclax and Bumetanide in drugs for fibrotic diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1 Screening C188-9, three compounds of Venetoclax and Bumetanide as a process for treating fibrous diseases

[0049] The main implementation process involved in this embodiment is as follows:

[0050] 1) Fifty small molecule compounds with strong affinity to LARP6-RRM were screened out by computer simulation;

[0051] 2) Treat NIH 3T3 fibroblasts with the small molecule compound screened in 1), and detect the changes of collagen mRNA by Real-Time PCR;

[0052] 3) Using the small molecular compound that affects collagen synthesis screened in 2), the direct combination of the small molecular compound and collagen is detected by micro-thermophoresis;

[0053] The main experimental parts involved in this embodiment are as follows:

[0054] 1. Screen out small molecular compounds with strong affinity to LARP6-RRM

[0055] The experimental steps are as follows:

[0056] Using Taosu Biology's classic known activity library (Cat. No.: L4000), 5,370 compounds with bi...

Embodiment 2

[0098] Example 2 Bumetanide inhibits bleomycin-induced pulmonary fibrosis in mice.

[0099] The main experimental parts involved in this embodiment are as follows:

[0100] 1. Detection of collagen gene expression by RIP-PCR

[0101] 1) Treat the cells with Bumetanide or solvent control.

[0102] 2) The cells in a 10 cm culture dish were cross-linked in ice, and irradiated with 400 mJ / cm2 UV for 5 minutes under the action of 1 ml of cold PBS.

[0103] 3) Discard PBS, add 500ul cold wash buffer (1×PBS, 0.1% SDS, 0.5% NP-40, 0.5% deoxycholic acid) containing 200U / ml RNase inhibitor (Takara) and protease inhibitor cocktail (Roche) Sodium), apply ice for 10 minutes.

[0104]4) Scrape off cells and put into 1.5ml tube.

[0105] 5) Centrifuge at 16000 g for 20 minutes at 4°C.

[0106] 6) Add RQ I (Promega) to a final concentration of 1 U / mol / l, incubate in a 37°C water bath for 5 minutes, and then cool on ice for 5 minutes.

[0107] 6) For co-immunoprecipitation, incubate over...

Embodiment 3

[0138] Example 3 Bumetanide inhibits collagen synthesis in human fibroblasts.

[0139] The main experimental parts involved in this embodiment are as follows:

[0140] 1. RIP-PCR detection of LARP6 binding collagen mRNA level

[0141] Method is detected with RIP-PCR in embodiment 2, and the results are shown in Figure 7A -C.

[0142] 2. RT-PCR detection of the effect of Bumetanide on the production of collagen mRNA

[0143] Method is detected with RT-PCR in embodiment 1, and the results are shown in Figure 8A -C.

[0144] Summary: The above results show that Bumetanide also has the function of inhibiting collagen production in human fibroblasts.

[0145] Based on the above-mentioned embodiments, the present invention starts from the library of natural active compounds, and through computer simulation screening, repeated research at the level of cell animals, it is found that in C188-9, Venetoclax and Bumetanide can be used as a new potential clinical treatment of fibrot...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides an application of C188-9, Venetoclax and Bumetanide in drugs for fibrotic diseases from perspective of clinic practice. A RNA recognition sequence (RNA recognition motif, RRM) region of LARP6 protein is taken as a docking target, and subject to computer virtual docking and simulated screening. Finally it is found by cellular and animal experiments that C188-9, Venetoclax andBumetanide (a potent quick-acting diuretic commonly used in clinic practice) combine with the RRM region of LARP6 protein to inhibit stability of collagen mRNA, thereby inhibiting collagen productionand further inhibiting fibrosis-related diseases in the process of occurrence and development of injury-induced fibrosis. The study of the invention enriches basic research on the pathogenesis of fibrosis-related diseases, and provides a new idea for deep exploration of essential causes of the fibrotic diseases. Meanwhile, the C188-9, Venetoclax and Bumetanide can be considered as a new potentialdrug for clinical treatment of the fibrotic diseases.

Description

technical field [0001] The invention belongs to the field of biotechnology, and specifically relates to the application of C188-9, Venetoclax and Bumetanide as drugs for preventing and treating fibrosis diseases. Background technique [0002] The main pathological changes of organ fibrosis are the increase of fibrous connective tissue and the decrease of parenchymal cells in organ tissues. Continuous fibrosis can lead to normal structural damage and physiological function decline, and even failure, which seriously threatens human health and life. Fibrosis plays an important role in diseases such as liver disease, kidney disease, idiopathic pulmonary fibrosis and heart failure. Fibrosis is also a major pathological feature of many chronic autoimmune diseases, such as scleroderma, rheumatoid arthritis, Crohn's disease, ulcerative colitis, myelofibrosis, and systemic lupus erythematosus. Fibrosis also plays an important role in tumor invasion and metastasis, chronic rejection ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K31/18A61K31/635A61P11/00A61P1/16A61P13/12A61P9/00A61P15/00A61P27/02A61P1/18A61P37/02A61P7/00A61P19/08C07C311/29C07C311/39C07D471/04
CPCA61K31/18A61K31/635A61P11/00A61P1/16A61P13/12A61P9/00A61P15/00A61P27/02A61P1/18A61P37/02A61P7/00A61P19/08C07C311/29C07C311/39C07D471/04
Inventor 余鹰左胜锴申毓军崔辉
Owner TIANJIN MEDICAL UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com