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Synergistic antitumor drug

An anti-tumor drug and anti-tumor technology, applied in the field of biomedicine, can solve problems such as unclear mechanism of action and unknown knowledge

Active Publication Date: 2018-10-23
GUANGZHOU VIROTECH PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the previous Chinese invention patent application 201510990705.7, chrysophanol and its derivatives were used as anti-tumor synergists of oncolytic viruses. The combination of the two can reduce the survival rate of tumor cells to 39.6%, but there is a big difference in their anti-cancer strength. Room for improvement
In addition, the mechanism of action of this combined application is still unclear, and it is not known which other substances that have not been clearly reported to enhance the efficacy of oncolytic viruses, which ones can have a synergistic effect with them, and the extent of the synergistic effect

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0080] Example 1 Multi-target screening of oncolytic virus M1 potentiator NU7441

[0081] Material:

[0082] High-glucose DMEM medium (purchased from Corning Company), human colorectal cancer cell HCT116 (purchased from ATCC cell bank), M1 virus (preservation number CCTCC V201423), 47 compounds with different targets (see Table 1, purchased from selleck company), an inverted phase-contrast microscope, and an automatic enzyme-linked detection microplate reader.

[0083] Table 1 Anticancer drugs with different targets

[0084]

[0085]

[0086] Method: such as figure 1 As shown in A

[0087] a) Cell culture: Human colorectal cancer HCT116 was grown in DMEM complete medium containing 10% FBS, 100U / ml penicillin and 0.1 mg / ml streptomycin; all cell lines were placed in 5% CO 2 , cultured and subcultured in a closed incubator with a constant temperature of 37°C (95% relative humidity), and observed the growth with an inverted microscope. The cells were subcultured every ...

Embodiment 2

[0093] Example 2 DNA-PK inhibitor NU7441 increases the oncolytic effect of oncolytic virus M1 on various tumor cells, but has no effect on normal cells

[0094] Material:

[0095] High glucose DMEM medium (purchased from Corning), human bladder cancer cell line T24 (purchased from ATCC cell bank), human glioma cell line U-87MG (purchased from ATCC cell bank), human pancreatic cancer cell line BxPC-3 (purchased from Shanghai Chinese Academy of Sciences Cell Bank), human liver cancer cell line Hep3B (purchased from ATCC Cell Bank), human colorectal cancer cell line HCT116 (purchased from ATCC Cell Bank), human normal liver cell line L-02 (gifted by Sun Yat-sen University), M1 virus (preservation number CCTCC V201423), DNA-PK inhibitor NU7441 (purchased from Selleck, USA), and an inverted phase-contrast microscope.

[0096] method:

[0097] Inoculation of cells, administration treatment: select logarithmic growth phase cells, DMEM complete culture medium (containing 10% fetal b...

Embodiment 3

[0100] Example 3 Combined treatment of various DNA-PK inhibitors and M1 oncolytic virus reduces the survival rate of cells Materials:

[0101] High-glucose DMEM medium (purchased from Corning), M1 virus (preservation number CCTCC V201423), human colorectal cancer cell HCT116 (purchased from ATCC), compound NU7441, NU7026 or KU0060648, (purchased from Selleck, USA), automatic enzyme-linked detection Microplate reader, tetramethylazolium blue (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT)

[0102] method:

[0103] a) Cell inoculation, administration treatment: select logarithmic growth phase cells, DMEM complete culture medium (containing 10% fetal calf serum, 1% double antibody) to make cell suspension, with 4 × 10 3 The density per well was seeded in a 6-well culture plate. After 12 hours, the cells were completely adhered to the wall. The experiment was divided into the control group, the NU7441 / NU7026 / KU0060648 alone group, the M1 infection group and t...

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Abstract

The invention belongs to the field of biomedicine and relates to synergistic antitumor drug, in particular to application of antitumor drug like DNA-PK (DNA-dependent protein kinase, DNA-PK) inhibitors and oncolytic viruses in preparing antitumor drug. It is found for the first time that the antitumor drug like the DNA-PK inhibitor with various targets can be used for preparing oncolytic virus antitumor synergists. The invention further relates to a drug composition containing the antitumor drug and the oncolytic viruses, drug sets comprising the antitumor drug and the oncolytic viruses and application of the antitumor drug and the oncolytic viruses in treating tumor, especially for tumor insensitive to the oncolytic viruses.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to the application of the combination of antitumor drugs such as DNA-PK protein inhibitors and oncolytic viruses in the preparation of antitumor drugs. Background technique [0002] Oncolytic virus is a kind of replication-competent virus that selectively 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. Our previous studies have shown that the virus M1 has high selectivity and good safety. Its application in the pr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K35/761A61K35/763A61K35/766A61K35/768A61P35/00
CPCA61K45/06A61P35/00A61K35/761A61K35/763A61K35/766A61K35/768A61K31/496A61K31/519A61K31/506A61K31/454A61K2300/00Y02A50/30
Inventor 颜光美肖晓贺嵩敏龚守芳林子青
Owner GUANGZHOU VIROTECH PHARMA
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