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Small molecule inhibitor and application thereof to inhibiting ornithine decarboxylase (ODC)

A small molecule inhibitor, ornithine decarboxylase technology, applied in the field of biomedicine, can solve the problems of high toxicity and side effects, high concentration, and weak binding ability

Active Publication Date: 2015-07-01
CHINA THREE GORGES UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, its binding ability to ODC is weak, and its concentration is very high, and because it is a suicide inhibitor that forms a covalent bond with ODC, its toxic and side effects are very large

Method used

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  • Small molecule inhibitor and application thereof to inhibiting ornithine decarboxylase (ODC)
  • Small molecule inhibitor and application thereof to inhibiting ornithine decarboxylase (ODC)
  • Small molecule inhibitor and application thereof to inhibiting ornithine decarboxylase (ODC)

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] The small molecule inhibitors involved are:

[0044] 2-[(hydroxyimino)methyl]-1-[2-(4-methoxyphenyl)-2-oxoethyl]pyridinium, the structural formula is shown in the formula.

[0045]

[0046] The activity detection method is as follows:

[0047] 1. Construction of human ODC prokaryotic expression plasmid

[0048] The gene sequence of human ODC was inserted into the pET28a plasmid through BamH I and Xho I restriction sites to construct the pET28a-hODC plasmid, which was verified by DNA sequencing.

[0049] Gene sequence of human ODC:

[0050] atgaacaactttggtaatgaagagtttgactgccacttcctcgatgaaggttttactgccaaggacattctggaccagaaaattaatgaagtttcttcttctgatgataaggatgccttctatgtggcagacctgggagacattctaaagaaacatctgaggtggttaaaagctctccctcgtgtcacccccttttatgcagtcaaatgtaatgatagcaaagccatcgtgaagacccttgctgctaccgggacaggatttgactgtgctagcaagactgaaatacagttggtgcagagtctgggggtgcctccagagaggattatctatgcaaatccttgtaaacaagtatctcaaattaagtatgctgctaataatggagtccagatgatgacttttgatagtgaagttgagttgatgaaagttgccagag...

Embodiment 2

[0071] The small molecule inhibitors involved are:

[0072] 2-(1-Hydroxyimino-ethyl)-1-[2-(3-methoxymethyl-phenyl)-2-oxo-ethyl]-pyridinium,

[0073] The structural formula is as shown in the formula:

[0074]

Embodiment 3

[0076] The small molecule inhibitors involved are:

[0077] 3-(2-Hydroxyimino-ethylideneaminooxy)-1-[2-(2-methoxymethyl-phenyl)-2-oxo-ethyl]-pyridinium,

[0078] The structural formula is as shown in the formula:

[0079]

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PUM

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Abstract

The invention belongs to the field of biomedicine and relates to a small molecule inhibitor of ornithine decarboxylase (ODC) and an application thereof. A novel small molecule inhibitor aiming at ODC is found through computer-aided high-throughput medicine screening. Verification of the effects of the novel small molecule inhibitor finds that the novel small molecule inhibitor has good inhibiting effects on ODC and can be especially used for inhibiting human-derived ODC, preventing, treating and diagnosing tumor diseases and pathogenic microorganism infection and developing and preparing tumor medicines or medicines against pathogenic microorganism infection.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to a small-molecule inhibitor of ornithine decarboxylase (ODC) and its application; in particular, it relates to a small-molecule inhibitor of human ornithine decarboxylase and its use in inhibiting and killing tumor cells Applications. Background technique [0002] Protein is one of the main components of organisms and the main substance to complete various life activities. Among various proteins, proteases are crucial to life activities, and almost all biochemical reactions in organisms are catalyzed by proteases. The activity of various proteases in organisms has a strict regulation mechanism. Once there is a problem with the regulation mechanism, the activity of proteases is too high, too low or completely inactivated, which will cause various diseases. Therefore, it has very important theoretical and practical significance to regulate the activity of protease by drugs to restore and ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D213/53A61K31/4425A61P35/00A61P33/02
CPCC07D213/30C07D213/53
Inventor 刘森王艳林占景琼
Owner CHINA THREE GORGES UNIV
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