Check patentability & draft patents in minutes with Patsnap Eureka AI!

Trpml1-specific agonist, its use as an autophagy inhibitor and preparation of a drug for treating tumors, and its pharmaceutical composition

An agonist, specific technology, applied in the field of biomedicine, to achieve the effect of prolonging life and strong lethal ability

Active Publication Date: 2020-09-29
XUZHOU MEDICAL UNIV
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In order to provide self-increased energy demand for tumor cells, autophagy signals are activated to continuously degrade their own proteins to meet the malignant proliferation needs of tumor cells. Therefore, the basal autophagy level of many types of tumor cells is significantly higher than that of normal cells. The experiment found that It was found that the use of such agonists to block autophagy can kill human tumor cells, but it has no significant lethal effect on normal human cells

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
  • Trpml1-specific agonist, its use as an autophagy inhibitor and preparation of a drug for treating tumors, and its pharmaceutical composition
  • Trpml1-specific agonist, its use as an autophagy inhibitor and preparation of a drug for treating tumors, and its pharmaceutical composition
  • Trpml1-specific agonist, its use as an autophagy inhibitor and preparation of a drug for treating tumors, and its pharmaceutical composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Example 1: Detection of MK6-83 inhibiting autophagy activity

[0051] 1. The experimental grouping is explained as follows

[0052] Blank control group: normal medium + 10% fetal bovine serum

[0053] Starvation treatment group: normal medium (without fetal bovine serum)

[0054] Test group 1: Bafilomycin A1 treatment

[0055] Experimental group 2: 1 μM MK6-83 treatment

[0056] Experimental group 3: 3 μM MK6-83 treatment

[0057] Experimental group 4: 5 μM MK6-83 treatment

[0058] Test group 5: 1μM MK6-83 combined with Bafilomycin A1 treatment

[0059] Test group 6: 5μM MK6-83 combined with Bafilomycin A1 treatment

[0060] Test group 7: 10 μM CQ treatment

[0061] Test group 8: 5μM MK6-83 combined with CQ treatment

[0062] Test group 9: 50 μM Rap treatment

[0063] 2. Experimental method

[0064] Subsequent processing and detection of cells in each group were performed by Western-blot detection method (Western blotting method). The specific methods are as ...

Embodiment 2

[0100] Example 2: Test of the lethality of MK6-83 on human pancreatic cancer cells Patu 8988t

[0101] 1. Test method

[0102] Cells were detected by trypan blue assay, specifically, cells in the control group and the cells in the drug-added group were digested with trypsin, and then mixed with a fixed volume of trypan blue reagent. Then use a pipette to draw 10 μL of the mixed solution, add it to a white blood cell counter, and place it under a microscope for counting. Cells stained with trypan blue were counted as dead cells, whereas cells were counted as live cells. The final ratio of viable cells to total cells in each group was counted as cell viability.

[0103] 2. Test results

[0104] Figure 4 It is the result of trypan blue staining of Patu 8988t cells treated with MK6-83 (5μM). Figure 4 It showed that the death rate of Patu8988t cells treated with 5μM MK6-83 was significantly increased compared with the control group, indicating that MK6-83 had a lethal effect...

Embodiment 3

[0108] Example 3: Test of the lethality of MK6-83 on human breast cancer cells MCF-7

[0109] 1. Test method

[0110] Cells were detected by trypan blue assay, specifically, cells in the control group and the cells in the drug-added group were digested with trypsin, and then mixed with a fixed volume of trypan blue reagent. Then use a pipette to draw 10 μL of the mixed solution, add it to a white blood cell counter, and place it under a microscope for counting. Cells stained with trypan blue were counted as dead cells, whereas cells were counted as live cells. The final ratio of viable cells to total cells in each group was counted as cell viability.

[0111] 2. Test results

[0112] Image 6 The results of the cell viability of breast cancer cell line MCF-7 treated with different concentrations of MK6-83 (the three data columns correspond to the blank control group CTL, the 1 μM MK6-83 drug-adding group, and the 5 μM MK6-83 drug-adding group, respectively) ; Figure 7 T...

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 a specific small-molecule agonist MK6-83 of an TRPML1 ion channel, and provides application of MK683 as an autophagy inhibitor and application thereof in preparing a drug for treating tumors. By inhibiting autophagy activity, the TRPML1 specific small-molecule agonist MK6-83 provided by the invention has strong deadly ability on various tumor cell systems comprising pancreatic cancer, breast cancer and gastric cancer under the action of no obvious toxicity on various normal tissue cells. Moreover, MK6-83 has obvious inhibiting effect on growth of breast cancer puff transplanted on mice, and remarkably prolongs the service life of a mouse with tumors. The specific small-molecule agonist MK6-83 solves the technical problem of killing cells of a normal tissue while killing the tumor cells as a result of anti-cancer cells and a cancer treatment way in the prior art.

Description

technical field [0001] The present application relates to the field of biomedicine, in particular, to a TRPML1 specific agonist, and also to the use of the specific agonist and a tumor therapeutic drug. Background technique [0002] Cancer has risen to become the leading cause of death in recent years as human lifespans increase. According to the "2018 National Latest Cancer Report" released by the National Cancer Center, there were 3.804 million new cases of malignant tumors in 2014, an average of more than 10,000 people were diagnosed with cancer every day, and 7 people were diagnosed with cancer every minute. Lung cancer is the most common malignant tumor in the country, followed by gastric cancer, colorectal cancer, liver cancer and breast cancer. Cancer has become the leading cause of death in our country. [0003] Regarding the treatment of cancer, scientists have carried out a lot of research work. New anticancer drugs are constantly being discovered. At present, ...

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 Patents(China)
IPC IPC(8): C07D333/34A61P35/00A61K31/4535
CPCA61P35/00C07D333/34
Inventor 王午阳
Owner XUZHOU MEDICAL UNIV
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com