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Application of perk inhibitor in the preparation of synergist of liver cancer medicine

A technology of inhibitors and drugs, applied in the field of liver cancer, can solve the problems of single immune method, limited curative effect, unsatisfactory anti-liver cancer treatment effect, etc., and achieve the effect of enhancing curative effect

Active Publication Date: 2022-04-05
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the efficacy of anti-PD-1 / PD-L1 therapy in HCC patients is still limited
[0004] The above clinical anti-liver cancer treatments are not effective, and can only prolong the survival time of patients with advanced liver cancer by about 3 months
Directly acting on tumors with targeted drugs is not effective in the treatment of liver cancer, ignoring the role of the body's immune system in the development of tumors
[0005] At present, the anti-PD-1 / PD-L1 immune method for liver cancer is too single, so the curative effect is limited. It is necessary to find other immunotherapy targets to improve the effect of anti-tumor therapy
The effect of single therapy on liver cancer is very limited, and it is necessary to explore the combination of immune and targeted therapy to improve the curative effect

Method used

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  • Application of perk inhibitor in the preparation of synergist of liver cancer medicine
  • Application of perk inhibitor in the preparation of synergist of liver cancer medicine
  • Application of perk inhibitor in the preparation of synergist of liver cancer medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1 Establishment of mouse liver orthotopic transplantation tumor model

[0035] 1. Experimental method

[0036] 1. The cell line used to establish liver orthotopic transplantation tumor in this experiment is Hepa1-6-Luciferase, cultured in DMEM medium + 10% fetal bovine serum (both purchased from Thermo Fisher Scientific), 37°C, 5% CO 2 In the system of , cultured to the third passage, the cells were harvested and used for in situ tumor formation in the liver;

[0037] 2, will be 7.5 × 10 5 Hepa1-6-Luciferase cells were mixed with 50% Matrigel (purchased from Trevigen, product number: 3432-001-01) to prepare a cell suspension, which was then transplanted into the left lobe of the liver of C57B / L6 mice under the envelope;

[0038] 3. On the 5th day after tumor bearing, the mice were divided into groups and treated with drug administration. The experimental grouping and administration methods are shown in Table 1:

[0039] Table 1 Experimental groups of C57B / L6...

Embodiment 2

[0051] Example 2 Establishment of subcutaneous liver cancer tumor model in NOD-SCID mice

[0052] 1. Experimental method

[0053] 1. The cell line used to establish liver orthotopic transplantation tumor in this experiment is Hepa1-6, cultured in DMEM medium + 10% fetal bovine serum (both purchased from Thermo Fisher Scientific), 37°C, 5% CO 2 In the system of , cultured to the third passage, harvested the cells for subcutaneous tumor formation;

[0054] 2, will be 7.5 × 10 5 Hepa1-6 was prepared into a cell suspension and injected subcutaneously into the right leg of NOD-SCID mice. On the 3rd day after tumor bearing, the mice were grouped and given drug treatment. The experimental grouping and administration method are shown in Table 2. .

[0055] Table 2 NOD-SCID mice anti-tumor treatment experimental groups:

[0056]

[0057] 3. From the 7th day, the tumor size of the mice was measured every 4 days. The length and width of the tumor were measured respectively, and t...

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Abstract

The invention discloses the application of PERK inhibitor in the preparation of synergist of liver cancer medicine. The study found that PERK is a target for the treatment of liver cancer. Blocking the activation of PERK by small molecular compounds is a new strategy for anti-liver cancer immunotherapy targeting the tumor-associated spleen, which has clinical application value. The present invention shows that the PERK inhibitor GSK2606414 exerts an anti-tumor effect by acting on the immune system in the spleen of mice with liver cancer. In addition, the PERK inhibitor GSK2606414 can significantly synergistically enhance the anti-PD-1 / PD-L1 and lenvatinib treatment effects on liver cancer, and can be used as a new type of liver cancer treatment drug for the treatment of liver cancer or to enhance the efficacy.

Description

technical field [0001] The invention relates to the technical field of liver cancer, in particular, to the application of a PERK inhibitor in the preparation of a synergist for liver cancer drugs. Background technique [0002] Primary hepatocellular carcinoma (hepatocellular carcinoma for short) is a common malignant tumor worldwide, with the morbidity and mortality ranking sixth and third respectively, and China is a high-incidence area of ​​liver cancer. In recent years, the incidence of liver cancer has increased significantly, seriously endangering human health and life safety. At present, the clinical treatment of liver cancer is very limited. For liver cancer that cannot be surgically removed, targeted drugs are usually used to directly act on the tumor to prolong the life of advanced patients, but the treatment effect is not satisfactory. However, in the tumor body, the immune system also plays a crucial role in tumor progression, and new anti-tumor treatments target...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61K39/395A61K31/47A61K31/519A61K45/06A61P35/00
CPCA61K45/00A61K39/39558A61K31/47A61K31/519A61K45/06A61P35/00A61K2300/00
Inventor 郑利民刘明宇吴翀
Owner SUN YAT SEN UNIV
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