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Autophagy improvement material and its application

A technology for use and metabolic disorders, applied in the treatment of autophagy-related diseases, can solve problems such as reducing insulin secretion, reducing islet cells, aggravating diabetes, etc., to reduce possible side effects and enhance autophagic activity.

Active Publication Date: 2022-04-29
溶酶技术有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] However, previously developed enhancers have not been studied for their involvement in metabolic disorders, so their effects on metabolic diseases, diabetes, etc. remain unclear
Instead, they may have adverse effects in the treatment of metabolic disorders, as their interactions with mTOR have not been clearly identified
Inhibition of mTOR can lead to enhanced autophagy; however, it may exacerbate diabetes as it may lead to a decrease in islet cells, which reduces insulin secretion

Method used

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  • Autophagy improvement material and its application
  • Autophagy improvement material and its application
  • Autophagy improvement material and its application

Examples

Experimental program
Comparison scheme
Effect test

experiment example

[0104] Materials and methods

[0105] Screening for autophagy enhancers. HEK293 cells in a 10cm culture dish were transfected with 5ug of pRLuc(C124A)-LC3(wt) or pRLuc(C124A)-LC3(G120A) plasmid (Faskas, Identification of novelautophagy regulators by a luciferase-based assay) with 10ul liposomes for the kinetics of autophagic flux. Autophagy 5:1018-1025, 2009). Stable transfectants were selected by culturing in the presence of 400 μg / ml G418 and clones with a wild / mutant normalized luciferase ratio <0.7 following 125 nM pamycin treatment for 6 h were isolated for library screening.

[0106] Luciferase assay. Firefly and Renilla luciferase assays were performed using the Dual Luciferase Reporter Assay System (Promega) according to the manufacturer's recommendations. Briefly, cells were lysed in 1x lysis buffer and subjected to a single round of freeze / thaw. Firefly luciferase was assayed after mixing 5 μL of lysate with 25 μL of Luciferase Assay Reagent II. Renilla lucifera...

Embodiment 1

[0126] Example 1. Synthesis of MSL Compounds of Formula 1.

[0127] The compound of formula 1 was purchased from Chembridge (Cas No. 831243-88-0).

Embodiment 2

[0128] Example 2. Preparation of 2-(2-chlorophenyl)-5-methoxy-4-(phenylsulfonyl)oxazole (compound of formula 2: MSL-7)

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Abstract

Compounds of Formula 1 or Formula 2 and uses thereof are disclosed herein. Based on the novel mechanism of autophagy activation by promoting lysosomal production, the compounds according to the present application can advantageously be used for the prevention or treatment of metabolic diseases, including type 2 diabetes, insulin resistance or obesity.

Description

technical field [0001] The present invention relates to a reagent for regulating autophagy and its use for treating diseases related to autophagy. Background technique [0002] Autophagy is a lysosome-dependent cellular process involving the degradation and regulation of the cell's own components and includes macroautophagy, microautophagy, and chaperone-mediated autophagy. Among them, macroautophagy (hereinafter referred to as autophagy) is characterized by the rearrangement of the subcellular membrane that separates the cytoplasm and organelles to form new organelle-like structures (macroautophagosomes). Autophagosomes fuse with lysosomes to form autolysosomes, where sequestered material is degraded by lysosomal enzymes (Klionsky, DJ, and Emr, SD (2000) Autophagy as a regulated pathway of cellular degradation. Science290, 1717-1721). The physiological roles of autophagy include quality control of organelles or cellular proteins and protection of nutrient balance (Mizushi...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/421C07D263/46G01N33/50G01N33/68
CPCA61K31/421C07D263/46G01N33/50G01N33/68A61P3/04A61P3/06G01N33/5008G01N33/6893G01N2500/10G01N33/5041G01N2500/02
Inventor 李明植林惠珍田灵医安镇熙H·S·帕吉列
Owner 溶酶技术有限公司
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