Application of a compound in the preparation of rtki and/or anti-angiogenic drugs

An anti-angiogenesis and angiogenesis technology, applied in the direction of anti-tumor drugs, drug combinations, pharmaceutical formulations, etc., can solve the problems that the use of tyrosine kinase has not been reported.

Inactive Publication Date: 2019-02-26
INST OF OCEANOLOGY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no report on the activity of bis-(2,3-dibromo-4,5-dihydroxyphenyl)-methane in inhibiting the activity of angiogenesis-related receptor tyrosine kinase and its anti-angiogenesis

Method used

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  • Application of a compound in the preparation of rtki and/or anti-angiogenic drugs
  • Application of a compound in the preparation of rtki and/or anti-angiogenic drugs
  • Application of a compound in the preparation of rtki and/or anti-angiogenic drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Bis-(2,3-dibromo-4,5-dihydroxyphenyl)-methane kinase activity study:

[0021] 1. Experimental drugs

[0022] Bis-(2,3-dibromo-4,5-dihydroxyphenyl)-methane (for the preparation process, please refer to the patent CN101597213B previously applied by the laboratory), using DMSO to aid dissolution, configured as a 50mg / ml storage solution for long-term storage, for experimental use The concentration was 5 μg / ml.

[0023] 2. Kinase Activity Detection

[0024] The kinase domains of FGFR1, FGFR2, FGFR3, FGFR4, PDGFR-α, PDGFR-β and VEGFR2 were assayed in buffers containing the following substances. The buffer contains 50mM HEPES (pH 7.0), 2mM MgCl2, 10mM MnCl2, 1mM NaF, 1mMDTT (dithiothreitol), 1mg / mL BSA (bovine serum albumin), 0.25μM biological peptide matrix (CAGAGAIETDKEYYTVKD). Add ATP at a final concentration of 12.5 μM to 90 μl buffer, and then add 5 μl of FGFR1, FGFR2, FGFR3, FGFR4, PDGFR-α, PDGFR-β and VEGFR2 respectively, and incubate at 37°C for 1 hour for kinase r...

Embodiment 2

[0027] Study on the proliferation of HUVEC with bis-(2,3-dibromo-4,5-dihydroxyphenyl)-methane:

[0028] 1. Cell line

[0029] Human umbilical vein endothelial cell line (HUVEC) was purchased from Shanghai Cell Bank, Chinese Academy of Sciences. In DMEM medium containing 10% fetal bovine serum at 37°C, with a volume fraction of 5% CO 2 1. Routine culture in the air under fully saturated humidity conditions, replace the medium after 48 hours, when the cell growth reaches saturation, digest with 0.25% trypsin and passage once every 2-3 days, and use logarithmic growth phase cells in the experiment.

[0030] 2. Experimental drugs

[0031] Bis-(2,3-dibromo-4,5-dihydroxyphenyl)-methane and Sunitinib, solubilized with DMSO and diluted in DMEM medium to 0.3, 0.6, 1.25, 2.5, 5, 10 and 6.25 μg / ml.

[0032] 3. Detection of HUVEC cell proliferation

[0033] Take HUVEC cells in the logarithmic growth phase by 4×10 3 Cells were seeded per well in a 96-well culture plate. Before use,...

Embodiment 3

[0036] Anti-angiogenesis of HUVEC by bis-(2,3-dibromo-4,5-dihydroxyphenyl)-methane:

[0037] Materials and Methods

[0038] 1. Experimental cells:

[0039] Same as Example 2

[0040] 2. Experimental drugs:

[0041] Same as Example 2

[0042] 3. Experimental method:

[0043] Matrigel containing growth factors was diluted in collagen (1:6, volume to volume), and kept at low temperature (on ice). This mixture was added to a 96-well cell culture plate (50ul / well), and incubated at 37°C for 1 hour to fully solidify the solution.

[0044]Inoculate these wells with HUVEC cell suspensions unmixed or mixed with 1.25, 2.5, 5, 10 μg / ml bis-(2,3-dibromo-4,5-dihydroxyphenyl)-methane and 6.25 μg / ml Sunitinib , continue to cultivate for 8h, and take pictures. IPP 6.0 software was used to measure the total capillary length of each well to evaluate the effect of bis-(2,3-dibromo-4,5-dihydroxyphenyl)-methane on capillary formation.

[0045] The results showed that bis-(2,3-dibromo-4,5-d...

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Abstract

The present invention belongs to the field of marine natural medicines, and relates to new medicinal uses of a Rhodomela confervoides effective component bis-(2,3-dibromo-4,5-dihydroxyphenyl)-methane. According to the present invention, the kinase activity experiment results prove that the compound affects the activity of an angiogenesis-related receptor tyrosine kinase, and can inhibit the activities of multiple kinases; with the human umbilical vein endothelial cell proliferation experiment and the angiogenesis experiment, the influence of the compound on the angiogenesis is observed, and the experiment results prove that the compound can effectively provide the anti-angiogenesis effect; and the bis-(2,3-dibromo-4,5-dihydroxyphenyl)-methane adopted as the pharmaceutical effective component can be added with the pharmaceutically acceptable carrier so as to prepare the anti-angiogenesis pharmaceutical composition.

Description

technical field [0001] The invention belongs to the field of natural medicines, in particular, it relates to the receptor tyrosine kinase inhibitory activity of bis-(2,3-dibromo-4,5-dihydroxyphenyl)-methane, an effective component of sea pine knotweed, and its Application in the preparation of anti-angiogenesis drugs. Specifically, the receptor tyrosine kinase inhibitory activity of bis-(2,3-dibromo-4,5-dihydroxyphenyl)-methane, an active ingredient of the sea pine knotweed, and its application in the preparation of anti-angiogenesis drugs. Background technique [0002] Angiogenesis refers to the complex biological process in which vascular endothelial cells undergo a series of changes such as activation, proliferation, migration and angiogenesis in the existing vascular system to form new microvessels under certain conditions. Since Folkman first proposed the theory of tumor angiogenesis in 1971, tumor angiogenesis has become one of the tumor markers. [0003] Studies hav...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/055A61P35/00
Inventor 史大永王帅玉王立军江波吴宁
Owner INST OF OCEANOLOGY - CHINESE ACAD OF SCI
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