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Application of curcumol in the preparation of nqo2 protein inhibitors

A protein inhibitor, curcumol technology, applied in the field of medicine, can solve the problems of poor survival and prognosis of patients, achieve the effect of convenient extraction and preparation, solve tumor drug resistance, and low price

Active Publication Date: 2021-02-05
JINAN UNIVERSITY
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Problems solved by technology

It has been reported in tumor research that NQO2 is highly expressed in liver cancer and kidney cancer. In our previous research, we found that NQO2 is highly expressed in lung adenocarcinoma patients, and the survival prognosis of patients with high NQO2 expression is poor.

Method used

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  • Application of curcumol in the preparation of nqo2 protein inhibitors
  • Application of curcumol in the preparation of nqo2 protein inhibitors
  • Application of curcumol in the preparation of nqo2 protein inhibitors

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Effect test

Embodiment 1

[0044] Embodiment 1: curcumol binds to NQO2 protein and inhibits NQO2 enzyme activity, curcumol and NQO2 binding sites are F126, I128, N161 and F178 amino acids

[0045] (1) Firstly, to determine the clinical manifestations of NQO2 in lung adenocarcinoma, we used immunohistochemical IHC to detect the expression of NQO2 in 94 cases of lung adenocarcinoma tissue and adjacent tissues (lung adenocarcinoma tissue and adjacent tissues came from the hospital) Condition. Specific steps are as follows:

[0046] The antibody used in the immunohistochemical experiment was NQO2 (Wuhan Proteintech Company), the dilution ratio was 1:3000, and the chip used was a lung adenocarcinoma 180-point tissue chip (HLugA180Su06, Shanghai Xinchao Biotech). Interpretation of IHC staining results: the staining ratio is represented by 0, 1, 2, 3, 4 respectively 6 indicates high expression of NQO2, and ≤6 indicates low expression of NQO2; statistical results were compared using Pearson’s chi-square test. ...

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Abstract

The invention discloses the application of curcumol in the preparation of NQO2 protein inhibitors. In the present invention, it is found that curcumol can be directly combined with NQO2 protein to inhibit NQO2 enzyme activity, and it is found that after the 126th, 128th, 161st or 178th amino acid of NQO2 protein is mutated to alanine, NQO2 is no longer combined with curcumol and NQO2 enzyme activity is affected. Therefore, curcumol can be used as an NQO2 protein inhibitor for the treatment of tumor drug resistance caused by high expression of NQO2. In addition, the present invention also provides an NQO2 protein mutant, which is at least one amino acid mutation alanine in the 126th, 128th, 161st and 178th amino acids of the NQO2 protein, which is a subsequent NQO2 protein inhibitor or anti-tumor Drug research provides an effective way.

Description

technical field [0001] The invention belongs to the technical field of medicine, in particular to the application of curcumol in the preparation of NQO2 protein inhibitors. Background technique [0002] Curcumol is one of the main active ingredients in the extract of Curcuma [1] , its structural formula is as shown in formula I: [0003] [0004] It was previously reported that curcumol has the functions of inhibiting tumor angiogenesis, inducing apoptosis, antiviral, antithrombotic, and antibacterial. [1] . In the field of tumor-related research, the effect of high concentration curcumol on breast cancer [2] , colorectal cancer [3] , stomach cancer [4] , liver cancer [5] , lung cancer [6] etc. have a certain inhibitory effect. But so far, there is no relevant report on the target protein of curcumol. [0005] Quinone oxidoreductase 2 (NQO2) can use reduced nicotinamide adenine dinucleotide (NADH) or reduced nicotinamide adenine dinucleotide phosphate (NADPH) to ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/35A61P35/00C12N9/02C12N15/53C12N15/70C12N1/21C12R1/19
CPCA61K31/35A61P35/00C12N9/0067C12N15/70C12Y112/05001
Inventor 何庆瑜张静汪洋
Owner JINAN UNIVERSITY
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