Application of KPNB1 inhibitor and protein degradation pathway inhibitor in preparation of anti-tumor drugs

A protein degradation and protein inhibition technology, applied in anti-tumor drugs, drug combinations, pharmaceutical formulations, etc., can solve the problems of inconclusive anti-cancer efficacy and off-target effects, inability to inhibit nuclear transport, and limited drugs.

Active Publication Date: 2019-05-07
CENT FOR EXCELLENCE IN BRAIN SCI & INTELLIGENCE TECH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the toxicity of KPNB1 inhibition on normal tissue cells still needs to be carefully evaluated.
Currently, the lack of KPNB1 inhibitors is a major limiting factor for targeting KPNB1 in cancer therapy
Recently, some small molecule peptide KPNA / KPNB inhibitors have been used to study nuclear translocation, however these inhibitors are not cell permeable
Ivermectin is a broad-spectrum KPNA / KPNB inhibitor but cannot inhibit KPNB1-mediated nuclear translocation alone
Karyostatin 1A is the first KPNB1 inhibitor discovered, but its anticancer efficacy and off-target effects are still inconclusive
Overall, drugs that inhibit KPNB1-mediated nuclear translocation are still limited

Method used

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  • Application of KPNB1 inhibitor and protein degradation pathway inhibitor in preparation of anti-tumor drugs
  • Application of KPNB1 inhibitor and protein degradation pathway inhibitor in preparation of anti-tumor drugs
  • Application of KPNB1 inhibitor and protein degradation pathway inhibitor in preparation of anti-tumor drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0078] Example 1, MTT method to detect the effect of KPNB1 inhibitor IPZ combined with inhibitors of protein degradation pathway on the survival of glioma cells

[0079] 1. Combined application of KPNB1 inhibitor IPZ and protein degradation pathway inhibitor Baf-A1

[0080] In this example, different concentrations (4uM, 8uM, 16uM) of IPZ were used for the KPNB1 inhibitor, and different concentrations of Baf-A1 were used for the inhibitor of the protein degradation pathway, as shown in the figure.

[0081] Glioma cell lines U87 and U251 were cultured in culture dishes with a diameter of 6 cm to about 30% confluence, and different concentrations of IPZ were added or not (blank control), and the cells were continued to be cultured for 4 days. Afterwards, they were cultured in a 96-well plate (manufactured by Corning, USA), with about 1500 cells per well and 150 μl of culture medium per well.

[0082] After the cells were treated with different concentrations of Baf-A1 alone or ...

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Abstract

The invention relates to an application of a KPNB1 inhibitor and a protein degradation pathway inhibitor in the preparation of anti-tumor drugs. According to the invention, the KPNB1 inhibitor and theprotein degradation pathway inhibitor are used in combination so as to have extremely excellent inhibition effect on treating tumors, particularly glioma. The aim of killing more tumor cells can be achieved by drug combination.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to the application of KPNB1 inhibitors and protein degradation pathway inhibitors in the preparation of antitumor drugs. Background technique [0002] Tumor is one of the diseases that threaten human health. So far, there is a lack of ideal treatment methods and drugs, and the development of new drugs is imminent. As an emerging method, gene therapy may become an effective means of tumor treatment in the near future. [0003] Glioma is a tumor that occurs in the brain or spinal cord. The most common site is the brain. It is called glioma because of its origin in glial cells. Glioma accounts for 30% of brain and central nervous system tumors and 80% of malignant brain tumors, and is a serious threat to human health. Glioma is usually treated with a combination of surgery, radiotherapy and chemotherapy. Glioma often occurs in the brain, and surgery requires a craniotomy, which takes a ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/517A61K31/7048A61K31/4706A61K38/05A61P35/00
Inventor 熊志奇朱志川李奎
Owner CENT FOR EXCELLENCE IN BRAIN SCI & INTELLIGENCE TECH CHINESE ACAD OF SCI
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