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Application of ubiquitin-binding enzyme E2 inhibitor and oncolytic virus in preparation of antitumor drugs

A technology of ubiquitin-conjugated enzymes and oncolytic viruses, which can be applied in the direction of anti-tumor drugs, drug combinations, and pharmaceutical formulations, and can solve the problems of different sensitivity of M1 virus and unsatisfactory oncolytic effect.

Active Publication Date: 2020-08-18
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, different tumors have different sensitivities to M1 virus, and for some tumors, when M1 virus is used alone, the oncolytic effect is not ideal.

Method used

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  • Application of ubiquitin-binding enzyme E2 inhibitor and oncolytic virus in preparation of antitumor drugs
  • Application of ubiquitin-binding enzyme E2 inhibitor and oncolytic virus in preparation of antitumor drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1B

[0032] Example 1 The combined treatment of BAY11-7082 and M1 virus significantly reduces the survival rate of human hepatocellular carcinoma line Hep3B

[0033] Material:

[0034] Human hepatocellular carcinoma Hep3B (purchased from ATCC), M1 virus (preservation number CCTCC V201423), high-glucose DMEM medium (purchased from Corning), multi-functional microplate reader.

[0035]In a preferred embodiment of the present invention, the ubiquitin-conjugating enzyme E2 inhibitor is Bay11-7082, and its structural formula is shown in Formula 1:

[0036]

[0037] Formula 1: Bay11-7082.

[0038] method:

[0039] a) Inoculation of cells, administration treatment: select logarithmic growth phase cells, DMEM complete culture medium (containing 10% fetal bovine serum, 1% double antibody) to make cell suspension, inoculate with the density of 4 × 103 cells in each hole 96-well culture plate. After 12 hours, the cells were completely adhered to the wall. The experiment was divided int...

Embodiment 2

[0045] A pharmaceutical composition for treating tumors, which comprises ubiquitin-conjugating enzyme E2 inhibitors and oncolytic viruses.

[0046] It can also be a medicine set for treating tumors, which comprises an ubiquitin-conjugating enzyme E2 inhibitor or a derivative thereof or a combination thereof, and an oncolytic virus. The difference between the drug set and the composition is that the ubiquitin-conjugating enzyme E2 inhibitor is different from the dosage form of the oncolytic virus, but is packaged independently (for example: pills, or capsules, or tablets or ampoules, containing the ubiquitin-conjugating enzyme E2 inhibitors; additional pills, or capsules, or tablets or ampoules, containing oncolytic virus). In some embodiments, an oncolytic virus, an inhibitor of ubiquitin-conjugating enzyme E2, and a combination of an oncolytic virus and an inhibitor of ubiquitin-conjugating enzyme E2 may also contain one or more adjuvants. The adjuvant refers to a component ...

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Abstract

The invention discloses an application of a ubiquitin-binding enzyme E2 inhibitor as an anti-tumor synergist / drug resistance reversal agent of oncolytic virus for the first time. The ubiquitin-bindingenzyme E2 inhibitor can significantly enhance the oncolytic effect of oncolytic virus by inhibiting ubiquitin-binding enzyme E2. The compound Bay11-7082 for inhibiting the activity of the ubiquitin-binding enzyme E2 to act on tumor cells in cooperation with oncolytic virus, especially M1 virus, and experimental results show that Bay11-7082 can be cooperated with oncolytic virus to enhance the anti-tumor effect.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and more specifically relates to the application of ubiquitin-conjugating enzyme E2 inhibitors and oncolytic viruses in the preparation of antitumor drugs. Background technique [0002] Oncolytic virus is a kind of replication-competent virus that targets and infects and kills tumor cells without damaging normal cells. Oncolytic virus therapy (oncolytic virotherapy) is an innovative tumor-targeted treatment strategy, which uses natural or genetically engineered viruses to selectively infect tumor cells and replicate in tumor cells to achieve targeted dissolution, The effect of killing tumor cells, but no damage to normal cells. [0003] Oncolytic virus M1 is a Getta-like virus of the Togaviridae alphavirus genus, isolated from mosquitoes of the genus Culex in Hainan Island, China. For example, Chinese invention patent application CN104814984A discloses that oncolytic virus M1 can selectivel...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K35/768A61K31/277A61P35/00A61P35/02
CPCA61K31/277A61K35/768A61K45/06A61P35/00A61P35/02A61K2300/00
Inventor 梁剑开蔡静林园苏兴文
Owner SUN YAT SEN UNIV
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