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Lead compound serving as ANKRD22 inhibitor and application thereof

A technology of leading compounds and inhibitors, applied in the field of compounds, can solve the problems such as ANKRD22 inhibitors that have not been reported yet, and achieve the effects of less resistance to drug resistance, saving experimental costs and less workload.

Active Publication Date: 2020-05-29
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

By searching databases such as Binding DB, DrugBank, patent database and Yaodu, we found that there are studies on polyclonal antibodies targeting ANKRD22. However, so far, no one has reported ANKRD22 inhibitors that have the effect of repairing gastrointestinal mucosal damage

Method used

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  • Lead compound serving as ANKRD22 inhibitor and application thereof
  • Lead compound serving as ANKRD22 inhibitor and application thereof
  • Lead compound serving as ANKRD22 inhibitor and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Example 1. Establishment of a computerized drug screening system for ANKRD22.

[0056] In this example, the computer drug screening system for ANKRD22 was constructed using the Chemdiv (Version 2019) database as a compound library for virtual screening, which contains 1,535,478 small molecule compounds, and the database has skeleton diversity. In order to ensure the global conformation of small molecules during the virtual screening process, this example uses the plug-in omega in the openeye software to generate small molecule conformations, and an average of about 50 conformations are generated for each small molecule. Finally, the molecules of Chemdiv were transformed into 50,679,311 molecular conformations and saved.

Embodiment 2

[0057] Example 2. Use the computer drug screening system of Example 1 to screen the compounds with high affinity to the active site of ANKRD22 from the database.

[0058] Molecular docking is one of the important methods of molecular simulation, its essence is the recognition process between two or more molecules, and the process involves spatial matching and energy matching between molecules. Molecular docking methods are widely used in drug design, material design and other fields. The virtual screening that this embodiment carries out is carried out on the workstation (CPU:40; Memory:64; SSD) that installs Ubuntu kylin 15.10 operating system, uses virtual screening software FRED to carry out virtual screening to the homologous modeling structure of ANKRD22, wherein operating parameters For example, both placement and scoring functions use default parameters. Translational Rotational

[0059] The step of molecular docking-based virtual screening is to screen the small ...

Embodiment 3

[0060] Example 3. ANKRD22 inhibitors have no obvious cytotoxicity within the effective dose range.

[0061] The toxic effect of the ANKRD22 inhibitor prepared in Example 1 on SGC7901 gastric adenocarcinoma cells was determined by the MTS method. The SGC7901 cells used were from the Shanghai Cell Bank of the Chinese Academy of Sciences.

[0062] The MTS analysis method was used to measure the toxic effect of the ANKRD22 inhibitor SGC7901 agent prepared in Example 1 on gastric adenocarcinoma cells. 52 kinds of ANKRD22 inhibitors were used as test samples, and the OD value was measured at 490 nm by an enzyme-linked immunosorbent monitor. Draw the cell growth inhibition rate curve as the abscissa and the absorbance value as the ordinate, such as figure 2 shown.

[0063] Among them, the specific steps of the MTS analysis method are:

[0064] (1). Cell inoculation: a single cell suspension was prepared with culture medium containing 10% fetal bovine serum, and 1000-10000 cells p...

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Abstract

The invention discloses a lead compound serving as an ANKRD22 inhibitor and application thereof. The lead compound is a small molecular compound with high affinity with an ANKRD22 natural substrate binding site. The affinity is (1-9)*10<-(5-12)>M. The application comprises the application of the lead compound as an active ingredient as an ANKRD22 inhibitor in preparation of a gastrointestinal mucosa repair protective agent. The invention also discloses application of the pharmaceutical composition in preparation of a tool medicine for researching gastrointestinal mucosa repair function and action mechanism. The ANKRD22 inhibitor provided by the invention has the effects of promoting the proliferation of gastrointestinal mucosa epithelial stem cells and indirectly activating a Wnt classicalpathway, and is beneficial to the rehabilitation of damaged gastrointestinal mucosa tissues of an organism.

Description

technical field [0001] The present invention relates to compounds and applications thereof, in particular to a lead compound as an ANKRD22 inhibitor and applications thereof. Background technique [0002] Human gastrointestinal mucosa is often exposed to a variety of injury factors, including endogenous factors such as high concentration of gastric acid, pepsin, duodenal fluid and exogenous factors such as non-steroidal anti-inflammatory drugs (NSAIDs), ethanol, drugs and Helicobacter pylori (Hp) infection. The gastrointestinal mucosa has the following defense and repair mechanisms, including mucus-bicarbonate barrier, mucosal barrier, submucosal blood flow, cell renewal, prostaglandin and growth factor protection, etc., which can resist the damaging effects of damaging factors and maintain the gastrointestinal mucosa integrity. [0003] Gastrointestinal mucosal damage is due to the enhancement of aggressive factors and / or the weakening of protective factors. Therefore, t...

Claims

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Application Information

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IPC IPC(8): C07D235/12C07D403/12C07D231/14C07D235/08C07D401/12C07D209/42C07D277/46C07D253/07C07D235/18C07D231/12C07D209/08C07D413/14C07D209/14C07D249/12C07D403/04C07D235/30C07D405/06C07D401/14C07D471/04C07D405/12A61K31/4184A61K31/415A61K31/4439A61K31/496A61K31/4155A61K31/421A61K31/53A61K31/404A61K31/454A61K31/4196A61K31/506A61K31/519A61P1/00A61P1/04A61P29/00
CPCC07D235/12C07D403/12C07D231/14C07D235/08C07D401/12C07D209/42C07D277/46C07D253/07C07D235/18C07D231/12C07D209/08C07D413/14C07D209/14C07D249/12C07D403/04C07D235/30C07D405/06C07D401/14C07D471/04C07D405/12A61P1/00A61P1/04A61P29/00
Inventor 朱永良柳景文朱悦
Owner ZHEJIANG UNIV
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