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Kinase inhibitor and application thereof in preparation of medicine for preventing and treating diseases caused by abnormal activation of TrkA/B/C kinase

A technology for kinase inhibitors, diseases, applied in the field of diseases caused by abnormal activation

Inactive Publication Date: 2021-06-11
天津仁雨生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, ferulic acid and sodium ferulate act as TrkA / B / C kinase inhibitors, and they are used in the prevention and treatment of diseases caused by abnormal activation of TrkA / B / C kinases, such as psoriasis, pain, inflammation, atherosclerosis Sclerosis, cancer, thrombosis, etc., there is no related report

Method used

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  • Kinase inhibitor and application thereof in preparation of medicine for preventing and treating diseases caused by abnormal activation of TrkA/B/C kinase
  • Kinase inhibitor and application thereof in preparation of medicine for preventing and treating diseases caused by abnormal activation of TrkA/B/C kinase
  • Kinase inhibitor and application thereof in preparation of medicine for preventing and treating diseases caused by abnormal activation of TrkA/B/C kinase

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] The molecular formula of ferulic acid is C 10 h 10 o 4 ; Structural formula is shown in formula (I):

[0038]

[0039] (I).

[0040] The molecular formula of sodium ferulate is C 10 h 9 o 4 Na; Structural formula is shown in formula (II):

[0041]

[0042] (II).

[0043] Using ferulic acid and sodium ferulate as active ingredients, adding pharmaceutically acceptable auxiliary materials, it can be prepared into liquid injections of various specifications according to conventional methods.

[0044] There are various administration routes of ferulic acid and sodium ferulate, such as injection administration, intracavitary administration and the like.

[0045] (1) Preparation of injections:

[0046] Ferulic acid sodium salt 200 mg, mannitol 700 mg, PEG3000 10 mg, distilled water 100 ml, make the pH value 7.0-7.5, filter the filtrate concentration to 3 mg / ml, pack in 2 ml per ampoule, freeze-dry to get the injection .

[0047] (2) Preparation of tablets:

...

Embodiment 2

[0052] Effect of ferulic acid and sodium ferulate on inhibition of TrkA, TrkB and TrkC kinases.

[0053] We used a series of concentrations of ferulic acid and sodium ferulate to act on human TrkA, TrkB and TrkC kinases in vitro, and found that they had different degrees of inhibition on the activities of the three kinases, suggesting that ferulic acid can be and sodium ferulate as active ingredients to prepare TrkA / B / C kinase inhibitors, the specific results are shown in Table 1.

[0054] Table 1 Inhibitory effect of ferulic acid and sodium ferulate on kinases in vitro

[0055]

[0056] Note: At present, due to the abnormal activation of TrkA, TrkB and TrkC kinases, they are widely found in diseases such as psoriasis, pain, inflammation, atherosclerosis, cancer and thrombosis. Because currently there are few inhibitor drugs aimed at inhibiting the abnormal activation of TrkA, TrkB and TrkC kinases, and most of them are chemically synthesized drugs with relatively large si...

Embodiment 3

[0058] To compare the effects of ferulic acid and sodium ferulate on the cytostatic effect of human normal skin immortalized keratinocyte cell line Hacat (in vitro psoriasis cell model function experiment).

[0059] According to the mechanism of action of PKM2, it is known that inhibiting the expression of PKM2 can inhibit the excessive proliferation of cells, incomplete differentiation, and active metabolism. Therefore, PKM2 has a good theoretical basis as a target for the development of psoriasis prevention and treatment drugs. Based on the above theory, we firstly applied ferulic acid (5 μg / ml) and sodium ferulate (5 μg / ml) to Hecat cells for 24 hours (at the same time, a blank control group was set), and then the total protein in each group of cells was extracted, and then The expression level of PKM2 protein in the cells was verified by Western Blot immunoblotting experiment, and the results indicated that after the Hecat cells were treated with ferulic acid (5 μg / ml) and ...

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Abstract

The invention discloses a TrkA / B / C kinase inhibitor, which can be used for preventing and treating diseases caused by abnormal activation of TrkA / B / C kinase. An in-vitro kinase inhibition experiment of the inhibitor shows that ferulic acid and sodium ferulate can inhibit the activity of TrkA / B / C kinase to different degrees, and the inhibition effect is relatively good. In addition, an in-vitro cell model killing experiment shows that the treatment effect of ferulic acid and sodium ferulate on tumor diseases with NTRK1 / 2 / 3 gene fusion mutation is obviously superior to that of a wild control group. Therefore, ferulic acid and sodium ferulate medicines can be used as effective components to prepare the TrkA / B / C kinase inhibitor, and can be used for preparing medicines for preventing and treating diseases caused by abnormal activation of human-derived TrkA / B / C kinase, including but not limited to psoriasis, pain, inflammation, atherosclerosis, cancers (such as malignant tumors caused by NTRK1 / 2 / 3 gene fusion mutation), thrombosis and the like.

Description

technical field [0001] The invention belongs to the technical field of medical applications, and relates to the preparation of TrkA / B / C kinase inhibitors with ferulic acid and sodium ferulate as active ingredients, which can be used to prepare and prevent diseases caused by abnormal activation of TrkA / B / C kinases, such as silver Psoriasis, pain, inflammation, atherosclerosis, cancer, thrombosis, etc. Background technique [0002] Tropomyosin receptor kinase (Trk), also known as neurotrophic receptor tyrosine kinase (Neurotrophic Receptor Tyrosine Kinase, NTRK), is the product of the trk gene, with a molecular weight of 120-160kD. As a single transmembrane glycoprotein, it is a member of the receptor tyrosine kinase (receptor tyrosinekinase, RTK) family. RTK family members have a similar structure, which consists of a large extracellular glycosylated ligand-binding region, a transmembrane region (TM), and an intracellular region (which can be divided into a near-membrane reg...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/192A61P35/00
CPCA61K31/192A61P35/00
Inventor 刘立仁潘博宇
Owner 天津仁雨生物科技有限公司