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Active peptide for inhibiting malignant tumors and enhancing treatment effect of chemical drug and application thereof

A malignant tumor, active peptide technology, applied in the direction of anti-tumor drugs, peptides, drug combinations, etc., can solve the problems of affecting clinical treatment effect, reducing chemotherapy sensitivity, high production cost, and achieving good industrialization prospects, good effects, and production. high cost effect

Active Publication Date: 2018-05-01
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] FGFs / FGFRs are the targets for the treatment of malignant tumors, and currently in the clinical development stage are mainly antibody proteins (the monoclonal antibody MFGR1877S in the phase I clinical trial stage and the fusion protein FP-1039 in the phase I / II phase) and small molecule inhibitors (AZD4547 and BGJ398 in phase II clinical trials), there are problems such as high production costs and large toxic and side effects
In addition, with the progression of malignant tumors, the decrease in chemosensitivity seriously affects the clinical treatment effect

Method used

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  • Active peptide for inhibiting malignant tumors and enhancing treatment effect of chemical drug and application thereof
  • Active peptide for inhibiting malignant tumors and enhancing treatment effect of chemical drug and application thereof
  • Active peptide for inhibiting malignant tumors and enhancing treatment effect of chemical drug and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0040] The synthesis of embodiment 1 active peptide

[0041] By the solid-phase peptide synthesis method, a 413A automatic peptide synthesizer (available from Perkin Elmer) was used to synthesize the peptide shown in the following sequence: Asn-Val-Phe-Thr-Val-Ser-Pro-Gly-Gly-Gly -Ser, wherein the amino acid residues are all L-type amino acids. The specific process of synthesis is as follows: first, the reactive group on the amino acid monomer is protected: the α-amino group of the amino acid is protected with 9-fluorenylmethoxycarbonyl (Fmoc); The chain protecting group is trityl (Trt), and the side chain protecting group for Ser and Thr is tert-butyl (tBu). Then, using N,N-diisopropylcarbodiimide / 1-hydroxybenzotriazole as an activating reagent, the protected amino acids were sequentially coupled for 40 min each time. In the presence of 15% (v / v) ethanedithiol / dimethyl sulfide / anisole (volume ratio 1:1:1), the peptide was mixed with trifluoroacetic acid (85% (v / v)) in Reac...

Embodiment 2

[0042] The influence of embodiment 2 active peptides on the survival rate of tumor cells

[0043] Gastric cancer cell line SGC-7901 (purchased from Nanjing Kebai Biotechnology Co., Ltd.) and bladder cancer cell line RT-112 (purchased from Guangzhou Geneo Biotechnology Co., Ltd.) were placed in wells of a 96-well plate. SGC-7901 cells were cultured overnight in 1640 medium supplemented with 10% (v / v) fetal bovine serum, while RT-112 cells were cultured overnight in DMEM medium supplemented with 10% (v / v) fetal bovine serum. The medium was discarded, and serum-free 1640 or DMEM medium was added to continue culturing for 24 h. The culture medium was discarded, and the active peptide prepared in Example 1 containing 20 ng / ml FGF9 (fibroblast growth factor 9, purchased from PeproTech Company) and different dilutions (1 μM, 4 μM, 16 μM) was added to each well in equal volume, respectively. And the 1640 or DMEM medium of the mixture of active peptide and 20ng / ml FGF9, incubate for 4...

Embodiment 3

[0045] The influence of embodiment 3 active peptides on cell migration

[0046] The effect of the active peptide prepared in Example 1 on the migration of SGC-7901 and RT-112 cells stimulated by FGF9 was detected. Briefly, SGC-7901 and RT-112 cells were seeded in 12-well plates and cultured overnight in 1640 medium and DMEM medium containing 10% (v / v) fetal bovine serum, respectively. The medium was discarded, and serum-free 1640 or DMEM medium was added to continue culturing for 24 h. When the confluency of the cells is about 80%, use a 200 μl pipette tip to draw three parallel straight lines vertically in the well. The culture medium was discarded, and washed three times with PBS buffer to remove the scraped floating cells. Grouped and treated for 48 hours, a blank control group, an active peptide (16 μM) group prepared in Example 1, a FGF9 (20 ng / ml) group, and an active peptide (16 μM)+FGF9 (20 ng / ml) group prepared in Example 1 were set up. The dynamic changes of the a...

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Abstract

The invention discloses active peptide for inhibiting malignant tumors and enhancing treatment effect of chemical drug and application thereof. The active peptide comprises the following sequence, namely Asn-Val-Phe-Thr-Val-Ser-Pro. The active peptide can be applied to specifically inhibit the proliferation, transfer and invasion of cells which are stimulated by fibroblast growth factors, inhibitthe generation of blood vessels, and enhance the therapy effect of the chemical drug, so as to treat various types of malignant tumors which are mediated by the fibroblast growth factors and receptorsthereof and of which the signal channels are abnormally activated, including but not limited to stomach cancer, bladder cancer, breast cancer, ovarian cancer, endometrial cancer, prostatic cancer, lung cancer, esophagus cancer or colon cancer and rectum cancer. The invention also discloses an antitumor medicine containing the active peptide and a preparation method.

Description

technical field [0001] The invention belongs to the technical field of peptides, in particular to an active peptide for inhibiting malignant tumors and enhancing the curative effect of chemical drugs and its application. Background technique [0002] Maintaining the homeostasis of body tissues depends on the regulation of complex growth factor signaling networks. The signaling network composed of fibroblast growth factors (FGFs) and their receptors (FGFR1-4) plays a role in regulating the interaction between cells. important role. According to sequence homology and phylogenetic differences, the discovered mammalian fibroblast growth factor family (FGFs, including FGF1-FGF10 and FGF16-FGF23) including 18 members can be divided into six subfamilies: FGF1 and FGF2; FGF3, FGF7, FGF10 and FGF22; FGF4, FGF5 and FGF6; FGF8, FGF17 and FGF18; FGF9, FGF16 and FGF20; FGF19, FGF21 and FGF23. Previous studies have confirmed that the members of the first five subfamilies belong to autoc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06A61K38/08A61P35/00
CPCA61K38/00C07K7/06
Inventor 吴晓萍王继重谭湘鹏
Owner JINAN UNIVERSITY
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