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Novel application of parthenolide, luteolin, chrysoeriol and ginsenoside Rg3

A technology of parthenolide and its use, which is applied in the field of medicine and can solve problems such as unclear

Inactive Publication Date: 2020-09-22
香港浸会大学深圳研究院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it is unclear whether ginsenoside Rg3 can reverse drug resistance in BRAF(V600E) mutant tumor cells
[0016] At present, there are no reports at home and abroad on whether the natural products parthenolide, luteolin, eriodinium, and ginsenoside Rg3 can reverse the resistance of tumor cells to BRAF (V600E) inhibitors

Method used

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  • Novel application of parthenolide, luteolin, chrysoeriol and ginsenoside Rg3
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  • Novel application of parthenolide, luteolin, chrysoeriol and ginsenoside Rg3

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Example 1, different concentrations of parthenolide, luteolin, golden eriodinamon and ginsenoside Rg3 are resistant to Effects on proliferation of BRAF mutant melanoma cells

[0053] 1.1. Experimental materials

[0054] (1) Parthenolide: purchased from Chengdu Mansite Biotechnology Co., Ltd.; accurately weigh a certain amount of parthenolide, and dissolve it into 20mM parthenolide solution (mother solution) with dimethyl sulfoxide (DMSO) , aliquoted, and placed in a -20°C refrigerator for later use.

[0055] (2) Luteolin: purchased from Chengdu Mansite Biotechnology Co., Ltd.; accurately weigh a certain amount of luteolin, dissolve it into 80 mM luteolin solution (mother solution) with dimethyl sulfoxide (DMSO), and pack , and put it in a -20°C refrigerator for later use.

[0056] (3) Auricillin: purchased from Extrasynthese Company; accurately weigh a certain amount of auricillin, dissolve it with dimethyl sulfoxide (DMSO) to a 40mM auricillin solution (mother so...

Embodiment 2

[0099] Example 2. Effect of parthenolide on the growth of drug-resistant BRAF (V600E) mutant melanoma in nude mice

[0100] 2.1. Experimental materials

[0101] Experimental animals: male BALB / c-nu / nu nude mice (about 8 weeks old), provided by the Animal Experiment Center of the Chinese University of Hong Kong. In the laboratory animal center of Hong Kong Baptist University in a sterile environment with constant temperature and pressure, they were used for the experiment after free access to food and water for 1 week.

[0102] A375-VR cells acquired resistance to vemurafenib: A375-VR melanoma cells resistant to vemurafenib were established in Example 1, followed by DMEM containing 1 μM vemurafenib and 5% FBS Culture cells to maintain their drug resistance.

[0103] Parthenolide Intraperitoneal Injection: Weigh 5 mg parthenolide and dissolve it in 1 mL of DMSO, then dilute to 20 mL with PBS to obtain 0.25 mg / mL parthenolide solution, filter and sterilize, subpackage, and st...

Embodiment 3

[0110] Embodiment 3, the effect of eriodiction on the growth of drug-resistant BRAF (V600E) mutant melanoma in nude mice

[0111] 3.1. Experimental materials

[0112] Experimental animals: male BALB / c-nu / nu nude mice (about 8 weeks old), provided by the Animal Experiment Center of the Chinese University of Hong Kong. In the laboratory animal center of Hong Kong Baptist University in a sterile environment with constant temperature and pressure, they were used for the experiment after free access to food and water for 1 week.

[0113] A375-VR cells acquired resistance to vemurafenib: A375-VR melanoma cells resistant to vemurafenib were established in Example 1, followed by DMEM containing 1 μM vemurafenib and 5% FBS Culture cells to maintain their drug resistance.

[0114] Golden eriodicillin intraperitoneal injection: Weigh 25mg golden eriodiction and dissolve it in 20mL PBS solution containing 5% PEG400 and 5% Tween 80 to obtain a 1.25mg / mL golden eriodicillin solution. S...

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Abstract

The invention provides novel application of parthenolide, luteolin, chrysoeriol and ginsenoside Rg3, and specifically relates to preparation of the compounds or derivatives of the compounds in preparation of drugs for preventing and / or treating drug-resistant BRAF (V600E) mutant-type tumors. It is found that proliferation of tumor cells resistant to BRAF (V600E)-targeted drugs can be inhibited through parthenolide, luteolin, chrysoeriol and ginsenoside Rg3, the tumor cells include inherent and acquired tolerant tumor cells, and growth of tumors is inhibited. It is shown through results that parthenolide, luteolin, chrysoeriol and ginsenoside Rg3 have the potential to be developed as the safe and effective drugs for treating the drug-resistant BRAF (V600E) mutant-type tumors.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to the application of natural products parthenolide, luteolin, erioidin and ginsenoside Rg3 in the preparation of drugs for preventing and / or treating drug-resistant BRAF (V600E) mutant tumors. Background technique [0002] Mitogen-activated protein kinases (MAPKs) are key signaling pathways in many cancers. BRAF is an important signaling molecule in the MAPK pathway. The BRAF mutation was first described in 2002, with V600E (valine at position 600 replaced by glutamic acid) being its most common mutation. According to reports, in papillary thyroid carcinoma (60.83%), hairy cell leukemia (58.33%), melanoma (48%), anaplastic thyroid carcinoma (35.96%), serous ovarian cancer (35%), breast cancer (13%) %), colorectal cancer (8.04%), glioma (6.5%), non-small cell lung cancer (3%) and other tumors exist BRAF (V600E) mutation. This mutation leads to persistent activation of BRAF, wh...

Claims

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Application Information

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IPC IPC(8): A61K31/365A61K31/352A61K31/704A61P35/00A61P35/02
CPCA61K31/704A61P35/00A61P35/02
Inventor 禹志领符秀琼刘雨溪
Owner 香港浸会大学深圳研究院
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