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

Induced nuclear receptor TR3 expressed cardiac glycoside compounds and use thereof

A compound and nuclear receptor technology, applied in the field of cardiac glycosides

Active Publication Date: 2008-12-17
JINAN UNIVERSITY
View PDF0 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, the high expression of members of the TR3 subfamily in the blood vessel wall may promote the pathogenesis of atherosclerosis, and the transcriptional activation of Nur77-regulated genes is involved in the inflammatory response of macrophages and the proliferation of vascular smooth muscle cells; it can be speculated that Nur77 located in the nucleus may promote atherosclerosis, Repression of transcriptional activation when located outside the nucleus may inhibit atherosclerotic lesion progression

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
  • Induced nuclear receptor TR3 expressed cardiac glycoside compounds and use thereof
  • Induced nuclear receptor TR3 expressed cardiac glycoside compounds and use thereof
  • Induced nuclear receptor TR3 expressed cardiac glycoside compounds and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1 Cardiac glycosides of the present invention and their preparation

[0030] Take 6Kg of dried stems of the Moraceae plant Antiaris toxicaria Lesch, coarsely crush it, and extract it under reflux with 8 times the amount of 60% ethanol three times for two hours each time, and concentrate the extract to obtain 300 g of ethanol extract. The extract was suspended in 6 liters of water, and extracted three times with equal volumes of ethyl acetate and n-butanol, respectively. The fraction of n-butanol (35g) was separated by silica gel column chromatography (φ5.0×60cm), and eluted with gradient chloroform-methanol-water system to obtain 5 fractions A-E. Among them, fraction B (2.9g) was separated by open ODS column chromatography (φ3.0×40cm) and eluted with 40% methanol to obtain two subfractions B1 and B2. Fraction B2 (930 mg) was separated by preparative reverse-phase high-performance liquid phase RP-18 column chromatography, and the mobile phase was 35% methanol to...

Embodiment 3

[0059] Example 3: Effects of Cardiac Glycoside Compounds of the Present Invention on TR3 Protein Expression

[0060] We used Western Blotting method for protein analysis. Cells were lysed with RIPA lysate and total protein was extracted. Prepare 10% SDS-polyacrylamide gels. The protein sample was transferred to a nitrocellulose membrane, and the electroporation condition was 100mA for 2h. Hybridization was performed according to the instructions of the Western blotting kit. Expose the film to an X-ray film in a cassette. Experimental results show that cardiac glycosides can induce the expression of TR3 protein. figure 2 It is the diagram of the influence of cardiac glycosides obtained in Example 1 on TR3 protein expression at different times. The expression of TR3 protein was induced by compounds 2, 4, and 5 respectively at 2, 3, 6, and 9 hours. It can be seen from the figure that the above-mentioned cardiac glycoside compounds can induce the expression of TR3 protein wi...

Embodiment 4

[0061] Embodiment 4: In vitro tumor inhibition experiment of cardiac glycosides of the present invention

[0062] We used the MTT method to test the inhibitory effect of compounds on tumor cells. Select confluence at 80%, logarithmic growth cells, digest with trypsin, transfer, centrifuge, remove the supernatant, and mix with newly prepared DMEM culture medium containing 10% FBS (inactivated fetal calf serum) hanging. Various cells in 1.0×10 4 10,000 / well was inoculated in a 96-well culture plate, and 5 different dilutions of the drug solution of the sample to be screened were added sequentially at the same time, and each dilution was repeated for 3 wells. At the same time, a solvent control of the same concentration and a negative control without drug addition were performed in parallel. , cultured at 37°C for 72 hours, stained with MTT, decolorized with DMSO, and measured OD 570 Calculate tumor growth inhibition rate IR (%)=(blank OD average value-administration group OD ...

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

PropertyMeasurementUnit
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
Login to View More

Abstract

The invention relates to a cardiac glycoside compound for inducing a nuclear receptor TR3 to express. The general formula of the compound of the invention is as follows: wherein, R1 is CH3, CHO or CH2OH; R2 is H or OH; R3 is H or OH; R4 is a linear sugar chain or a branch sugar chain consisted by saccharide. The cardiac glycoside compound of the invention can induce the nuclear receptor TR3 to express, thus being capable of being used as a revulsant to be applied to the preparation of drugs which are used for preventing and treating cancer, hepatitis, atherosclerosis, etc.

Description

technical field [0001] The invention relates to a cardiac glycoside compound for inducing expression of nuclear receptor TR3 and application thereof. Background technique [0002] TR3 is an orphan nuclear receptor encoded by the human NR4A1 gene. The currently cloned mouse genes include Nur77 (mouse) and NGF-IB (rat), which are related to two other close relatives identified in recent years, NOT-1 and NOR-1s form a striking subfamily. TR3 is an immediate early gene, many external signals, including various growth factors (such as nerve growth factor, epidermal growth factor, fibroblast growth factor, serum growth factor), calcium ionophore, KCl, phorbol ester, retinoic acid Family, Tax protein and so on can induce the expression of TR3. The structure of TR3 family members has relatively unique structural characteristics. Its transcriptional activity is mainly controlled by the transcription activation region AF1 at the N-terminus, and the pocket structure of the ligand-bin...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07J17/00A61K31/585A61P35/00A61P1/16A61P9/10
Inventor 姚新生张晓坤姜苗苗曾锦章张雪王光辉戴毅何加友
Owner JINAN UNIVERSITY
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