Application of FGFR2b inhibiting molecule in preparation of drug for treating PAF-mediated disease

A FGF-7, molecular technology, applied in the application field of disease drugs, can solve the problems of limited improvement of patient survival rate, failure to clarify the causes of occurrence and development, inability to treat diseases, etc., to achieve easy toxic side effects and easy evaluation. , targeted effect

Pending Publication Date: 2020-10-13
汪炬
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Glucocorticoids can prevent the immune system from overreacting to cause further damage to the body, but it also has huge side effects, including but not limited to aggravated infection, osteoporosis, cardiovascular system and digestive system complications
On the other hand, supportive therapy only maintains the life of the patient, but cannot treat the disease, and has very limited effect on improving the survival rate of the patient.
[0005] Since the cause of the occurrence and development of the disease has not been clarified, it has not been possible to develop a targeted treatment for ARDS, so it is imminent to develop innovative therapeutic drugs

Method used

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  • Application of FGFR2b inhibiting molecule in preparation of drug for treating PAF-mediated disease
  • Application of FGFR2b inhibiting molecule in preparation of drug for treating PAF-mediated disease
  • Application of FGFR2b inhibiting molecule in preparation of drug for treating PAF-mediated disease

Examples

Experimental program
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Effect test

Embodiment 1

[0028] This embodiment 1 provides a short peptide and its pharmaceutical preparation, which is a sequence obtained by truncating 5-12 amino acids of the extracellular segment of FGFR (SEQ NO ID.52) and undergoing 0-2 point mutations. The 5-12 amino acids truncated from the extracellular segment of FGFR are spatially adjacent amino acids truncated according to the three-dimensional structure of the extracellular segment of FGFR. Specifically, the designed amino acids are represented by EWVRTD (PI9, SEQ NO ID.9), ELSGRA (PI15, SEQ NO ID.15), QDVDS (PI29, SEQ NO ID.29), VFSTTGV (PI47, SEQ NO ID. 47) as the center, the amino acid sequences are added or deleted at both ends, and the short peptides are named PI1-PI51.

[0029] Wherein, the amino acid sequence of the extracellular segment of FGFR (from the amino terminal to the carboxyl terminal) is as follows (SEQ NO ID.52):

[0030] APYWTNTEKMEKRLHAVPAANTVKFRCPAGGNPMPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDVVER...

Embodiment 2

[0037] In Example 2, it was found that FGF7 regulates the expression of Platlet Activating Factor (PAF) through lipidomics research.

[0038] 1.1 Preparation of processed samples

[0039] Culture SZ95 human sebocytes, when the cells grow to 70% full, digest the cells with trypsin for 5min, discard the trypsin, add SEB-1 complete medium (SEB-1 sebocyte medium + 10% fetal bovine serum, Zenbio, USA) terminates the digestion of trypsin, blows the cells down, mixes them evenly to form a cell suspension, and counts them. The cells are grouped as shown in the table below, and each group has 3 repetitions. The primary sebocytes are plated to 10 cm for culture In a dish, add 3.7×10 to each well 5 add 10mL SEB-1 complete medium, adhere to the wall culture, change the culture medium every 48h, when the cells grow to 70% full, add serum-free medium (SEB-1 medium) to starve for 12h, discard the culture medium Base, the cells were treated as shown in Table 2, the culture medium without an...

Embodiment 3

[0066] 20 μM PAF (Shanghai Yubo Biotechnology Co., Ltd.) was used to induce SZ95 human sebocytes, and then ELISA was used to detect the effect of PAF on the expression of pro-inflammatory cytokines at different times. The detection steps are as follows:

[0067] ①Sample collection: transfer the cell culture solution to EP tubes, centrifuge in a pre-cooled refrigerated centrifuge at 4°C and 12,000 rpm for 5 minutes, take the supernatant, and distribute it in EP tubes, 400 μL for each EP tube, and store in - 20°C refrigerator, take it out and let it melt at room temperature before use;

[0068] ②According to the instructions of IL-6ELISA detection kit and IL-8ELISA detection kit of Beijing Sizhengbai Biotechnology Co., Ltd., take the kit and experimental samples stored at 4°C to room temperature for 30 minutes, and equilibrate to room temperature;

[0069] ③Add the sample to be tested into the corresponding enzyme-labeled well, 100 μL per well, seal the reaction well with seali...

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Abstract

The invention discloses application of a FGFR2b inhibiting molecule in preparation of a drug for treating a PAF-mediated disease. The application is a research result obtained on the basis of that aninventor of the invention discovers that FGF-7 can induce generation of a platelet activating factor PAF. The inventor of the invention discovers that the rising of a level of a proinflammatory factorcan be induced after the PAF is generated, then, an inflammatory reaction is initiated, a molecule inhibiting bonding between the FGF-7 and FGFR2serves as a competitive antagonist of FGF7 and is bonded to a specific receptor FGFR2b of the FGF7 so as to prevent the FGFR2b from being activated into phosphorylated FGFR2b, and an excessive inflammatory reaction can be effectively inhibited, so that ARDS symptoms are treated, and lung fibrosis can be improved.

Description

technical field [0001] The invention belongs to the field of medicine and biology, and particularly relates to the application of FGFR2b inhibitory molecules in the preparation of medicines for treating diseases mediated by PAF. Background technique [0002] Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by refractory hypoxemia caused by intrapulmonary and / or extrapulmonary causes, and has attracted much attention due to its high mortality. Its pathogenesis involves an uncontrolled patient's own immune defense response and results in inflammation, endothelial injury, enhanced coagulation, reduced fibrinolysis, and fibroproliferation, and is a clinical syndrome caused by various pathogens. In 1994, the American-European Consensus Conference Committee on ARDS recommended a definition of the disease; criteria included: (1) acute onset, (2) bilateral infiltrates on chest radiograph, (3) pulmonary artery wedge pressure ≤18 mm Hg or lack of Clinic...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K38/08A61P11/00A61P7/10A61P9/10A61P35/04A61P25/28A61P25/16A61P31/04A61P31/14
CPCA61K45/00A61K38/08A61P11/00A61P7/10A61P9/10A61P35/04A61P25/28A61P25/16A61P31/04A61P31/14
Inventor 汪炬
Owner 汪炬
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