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Novel use of amine hydrochloride compound

A hydrochloride compound and compound technology, applied in the field of compounds, can solve the problems of small number of small molecular compounds and poor specificity, etc.

Inactive Publication Date: 2019-02-15
TIANJIN UNIVERSITY OF SCIENCE AND TECHNOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But so far, the number of small molecule compounds that have been found to induce TFEB is small, and the specificity is poor

Method used

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  • Novel use of amine hydrochloride compound
  • Novel use of amine hydrochloride compound
  • Novel use of amine hydrochloride compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] (1) Screening of drugs that promote TFEB nuclear entry

[0033] ① 96-well plate plating: Collect cells, adjust the concentration of the cell suspension according to the counting results of the hemocytometer, plate to make the density of the cells to be tested 8000 / well, add 200 μL of medium to each well, and fill the edge of the 96-well plate with PBS.

[0034] ②5% CO 2 After incubation at 37° C. for 24 h, drugs (dimethyl sulfoxide (DMSO), compound I) were added at a final concentration of 5 μM.

[0035] ③ After 24 hours of dosing, take pictures with a fluorescence microscope and observe. figure 1 The results showed that compound I could significantly promote the nuclear entry of TFEB-GFP in HeLa cells stably expressing TFEB-GFP.

[0036]

[0037] (2) Nucleoplasmic separation technology

[0038]Using the cytoplasmic protein extraction reagents CERⅠ and CERⅡ, under the condition of low osmotic pressure, the cells are fully expanded, and then the cell membrane is de...

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Abstract

The invention provides a novel use of an amine hydrochloride compound. The amine hydrochloride compound is a small molecule compound which is found by screening a small molecule compound library by establishing a HeLa cell screening system capable of stably expressing TFEB-GFP. The small molecule compound is a selective 5-HT reuptake inhibitor (1S-cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthyridine hydrochloride, and can effectively promote the nuclear translocation of a transcription factor TFEB.

Description

technical field [0001] The present invention relates to a new use of a compound, especially a new use of an amine hydrochloride compound. Background technique [0002] Transcription Factor EB (TFEB) is the first identified basic-helix-loop-helix leucine zipper (bHLH-Zip) class of the MiTF / TFE family Transcription factors play an important regulatory role in the biosynthesis and metabolism of lysosomes, are important regulators of autophagy, and have a wide range of physiological functions. [0003] The cellular location and activity regulation of TFEB are related to its phosphorylation modification state. Under nutrient-rich conditions, TFEB mainly exists in the cytoplasm in an inactive state, but under conditions of starvation or lysosomal dysfunction, TFEB rapidly translocates to the nucleus. and activate the transcription of its target genes. TFEB protein can be phosphorylated at least 20 sites, among which two serine residues, Ser142 and Ser211, play a key role in its ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/135A61P35/00A61P43/00
CPCA61K31/135A61P35/00A61P43/00
Inventor 刁爱坡李薇刘振兴
Owner TIANJIN UNIVERSITY OF SCIENCE AND TECHNOLOGY
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