RBP2 enzyme inhibitor small molecular compound WXSA-072A as well as preparation method and anti-gastric cancer application thereof

A technology of WXSA-072A and small molecule compounds, which is applied in small molecule compounds of RBP2 enzyme inhibitors and anti-gastric cancer applications, can solve the problems of poor cell permeability, lack of selectivity, complicated interpretation of biological research, etc., and achieve migration ability Reduced, novel structure, and the effect of inhibiting RBP2 enzyme activity

Inactive Publication Date: 2019-03-08
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Other molecules inhibit KDMs in a competitive manner with 2-OG, such as N-oxalylglycine (NOG), 2,4-pyridinedicarboxylic acid (2,4-PDA), lack of selectivity or poor cell permeability, making the use of these Complicating the Interpretation of Biological Studies of Compounds

Method used

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  • RBP2 enzyme inhibitor small molecular compound WXSA-072A as well as preparation method and anti-gastric cancer application thereof
  • RBP2 enzyme inhibitor small molecular compound WXSA-072A as well as preparation method and anti-gastric cancer application thereof
  • RBP2 enzyme inhibitor small molecular compound WXSA-072A as well as preparation method and anti-gastric cancer application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] The preparation of embodiment 1 WXSA-072A

[0035] One, the preparation of intermediate 2

[0036] Weigh (2,2'-bipyridyl)-4,4'-dicarboxylic acid dimethyl ester (0.55 g, 2.0 mmol) into a conical flask, add tetrahydrofuran:methanol=1:1 total 40mL, stir at room temperature for 15 Minutes; then 2 mL of 1 mol / L potassium hydroxide aqueous solution was added dropwise into the Erlenmeyer flask under an ice bath, and continued stirring at room temperature overnight. After the reaction was completed, the solvent was evaporated to dryness under reduced pressure, 50 mL of water was added thereto, and then 1 mol / L of dilute hydrochloric acid was added until the solid was precipitated, the filter residue was taken by suction filtration, 40 mL of dichloromethane was added to the filter residue, and the filter residue was taken by suction filtration to obtain the crude product of Intermediate 2 . White solid, yield 18%.

[0037] .

[0038] Two, the preparation of intermediate 3 ...

Embodiment 2

[0045] Example 2 Detecting the Effect of Compounds on RBP2 Enzyme Substrates in Gastric Cancer Cells (Western blot)

[0046] Purpose:

[0047] The effect of the test compound on the RBP2 enzyme substrate H3K4me3

[0048] Experimental Materials:

[0049] RPMI 1640 medium was purchased from Gibco;

[0050] Fetal bovine serum was purchased from Gibco;

[0051] DMSO was purchased from Sigma;

[0052] EpiQuik Total Histone Extraction Kit (OP-0006-100) was purchased from Epigentek Group;

[0053] Pierce ® BCA Protein Assay Kit was purchased from Thermo fisher scientific company

[0054] laboratory apparatus:

[0055] HF safe biological safety cabinet,

[0056] MCO-15AC carbon dioxide incubator, Japan Sanyo SANYO,

[0057] Polyacrylamide gel vertical electrophoresis tank, Liuyi Instrument Factory, Beijing, China

[0058] Test drug:

[0059] Compound WXSA-072A was prepared as a stock solution with DMSO, with a final concentration of 200mM, diluted with incomplete medium fo...

Embodiment 3

[0069] Example 3 Detection of compound's effect on migration ability in gastric cancer cells (Transwell)

[0070] Purpose:

[0071] The effect of detection compounds on the migration ability of gastric cancer cells

[0072] Experimental Materials:

[0073] RPMI 1640 medium was purchased from Gibco;

[0074] Fetal bovine serum was purchased from Gibco;

[0075] DMSO was purchased from Sigma;

[0076] Corning Transwell 3542 chamber was purchased from Beijing Suo Laibao Technology Co., Ltd.

[0077] laboratory apparatus:

[0078] HF safe biological safety cabinet,

[0079] MCO-15AC carbon dioxide incubator, Japan Sanyo SANYO,

[0080] Olympus CKX53 biological microscope, Shanghai Puhe Optoelectronics Technology Co., Ltd.,

[0081] Test drug:

[0082] For compound WXSA-072A, the sample was prepared into a mother solution with DMSO, with a final concentration of 200mM. When used, it was diluted with incomplete medium, and the final concentration of DMSO did not exceed 0.1%...

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PUM

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Abstract

The invention provides a RBP2 enzyme activity inhibition small molecular compound WXSA-072A designed and synthesized for enzyme active sites, and provides a preparation method thereof. The experimentproves that the compound can significantly increase an H3K4me3 protein level in gastric cancer cells BGC-823 of a human, has an obvious function of inhibiting the RBP2 enzyme activity, and can reducea metastasizing ability of the gastric cancer cells BGC-823 of the human. According to the invention, the RBP2 enzyme inhibitor small molecular compound can be used for preparing anti-gastric cancer drugs as a gastric cancer inhibitor. The formula is shown in the specification.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to an RBP2 enzyme inhibitor small molecule compound WXSA-072A, a preparation method thereof and an anti-gastric cancer application. Background technique [0002] Antineoplastic drugs commonly used in clinical practice are mainly cytotoxic drugs, most of which have unavoidable disadvantages such as poor selectivity, strong toxic and side effects, and easy drug resistance. In recent years, with the rapid development of life science research, various basic processes such as signal transduction in malignant tumor cells, regulation of cell cycle, induction of apoptosis, angiogenesis, and interaction between cells and extracellular matrix are being investigated. The gradual clarification has brought about a huge change in the research and development concept of anticancer drugs. Therefore, using some key enzymes / proteins related to tumor cell modification as drug targets, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D213/81A61K31/444A61P35/00
CPCA61P35/00C07D213/81
Inventor 贾继辉展鹏刘新泳陈春燕贾夏夏张硕俞霁王学顺
Owner SHANDONG UNIV
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