Application of epigallocatechin-3-gallate in preparation of antitumor drug

A technology of epigallocatechin and gallate, applied in the fields of medicine and genetic engineering, can solve problems such as EGCG that have not yet been seen, and achieve the effects of not being resistant to drug resistance and inhibiting the growth of liver cancer cells

Inactive Publication Date: 2012-07-04
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] So far, there are no reports about the use of EGCG as a CYPJ inhibitor in tumor therapy, especially in the treatment of liver cancer, cervical cancer or nasopharyngeal cancer

Method used

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  • Application of epigallocatechin-3-gallate in preparation of antitumor drug
  • Application of epigallocatechin-3-gallate in preparation of antitumor drug
  • Application of epigallocatechin-3-gallate in preparation of antitumor drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Example 1 Virtual Screening of CYPJ Small Molecule Inhibitors

[0056] The present invention retrieves the X-ray diffraction crystal structure of human CYPA protein (PDB code: 1CWA) through the PDB protein structure database. This structure is the complex crystal structure of CYPA and its natural inhibitor cyclosporin A (CsA). From this structure, the active site of CYPA was determined, and several key amino acid sites in the active site that could be inhibited by CsA were determined.

[0057] In this example, for the active site of CYPJ (PDB code of CYPJ protein crystal: 1XYH; provided by Shanghai Institute of Organic Chemistry), according to the molecular docking method, several small molecule databases were virtual screened, and the binding free energy of AutoDock Vina was used to The binding affinities of the relevant small molecules were ranked (see Table 1). It was found that epigallocatechin gallate (EGCG) ranked higher with CYPA and CYPJ, and its affinity for ...

Embodiment 2

[0061] Example 2 Validation of virtual screening results using molecular docking

[0062] Calculate the binding free energy of EGCG, CsA and CYPA, CYPJ AutoDock Vina. Such as Figure 1-Figure 4 As shown, both EGCG and CsA can be combined at the active centers of CYPA and CYPJ, and some groups are inserted into the pockets of the active centers. Figure 4 The structure of the CsA-CYPA complex calculated by AutoDock Vina docking is consistent with the crystal structure (1CWA), indicating that the molecular docking method of the present invention is reliable. The binding energy of EGCG and CYPJ is -8.9 kcal / mol; the binding energy of EGCG and CYPA is -7.7 kcal / mol; the binding energy of CsA and CYPJ is -7.2 kcal / mol; the binding energy of CsA and CYPA is -7.3 kcal / mol mol. The above results show that EGCG can bind to CYPA and CYPJ, and the binding ability to CYPJ is stronger. It is worth mentioning that although CsA can also bind to CYPA and CYPJ, it has no higher selectivi...

Embodiment 3

[0064] Example 3 Validation of virtual screening results using BIACORE Molecular Interaction Instrument

[0065] The BIACORE Molecular Interaction Instrument is based on surface plasmon resonance technology to track the interaction between biomolecules without any markers, thus ensuring the authenticity of the experimental results to the greatest extent. During the experiment, the target biomolecules (CYPA, CYPJ proteins) were immobilized on the surface of the sensor chip, and then the small molecule compounds were dissolved in a solvent and flowed over the surface of the chip. The monitor can track the changes in the whole process of binding and dissociation between molecules in the detection solution and target biomolecules on the chip surface in real time. Binding data via BIACORE ( Figure 5-8 ), finally calculated the affinity dissociation constant KD value of EGCG and CYPA of the present invention to be 3.82×10 -7 M, the KD value with CYPJ is 6.80×10 -7 M; The KD...

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Abstract

The invention belongs to the fields of medicine and gene engineering, relates to a new medicinal application of epigallocatechin-3-gallate EGCG, and particularly relates to an application of epigallocatechin-3-gallate in the preparation of antitumor drugs. Cell experiments demonstrate that the epigallocatechin-3-gallate is a CYPJ inhibitor, and has the capability of inhibiting liver cancer cell growth; a large dose of EGCG basically has no toxicity to liver, kidney and heart. Experiment results also show that when EGCG is added into a culture solution of tumor cells, the proliferation of tumor cells is inhibited; the tumor cells are blocked at the G1 stage; the activity of CYPJ is inhibited; the activation of an Erk signal path by CYPJ protein is blocked. The epigallocatechin-3-gallate of the invention can be used for the preparation of antitumor drugs, especially anti-liver cancer drugs; and the drugs are designed aiming at cell target points, and drug resistance is not easy to generate.

Description

technical field [0001] The invention belongs to the fields of medicine and genetic engineering, and relates to a new medical application of epigallocatechin gallate (EGCG), in particular to the application of epigallocatechin gallate (EGCG) in preparing antitumor drugs. Background technique [0002] It is known that Cycliphilins (CyPs) are ubiquitously distributed intracellular proteins that exist in plants, bacteria and mammals and are highly conserved. They were originally discovered as cell receptors of cyclosporine A. Cyclosporin A (CsA) is a cyclic polypeptide containing 11 amino acids isolated from fungal metabolites. It is an immunosuppressant for organ transplantation and autoimmune diseases. It has been widely used in Clinical, annual sales of more than 5 billion US dollars. At present, CsA has also been used in tumor treatment, and it is mainly used in combination with other anticancer drugs such as paclitaxel, doxorubicin, vincristine, etc., to enhance the antitu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/353A61P35/00
Inventor 余龙刘祖龙张明君朱恒锐唐丽莎
Owner FUDAN UNIV
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