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Compounds targeting actin-binding protein transgelin-2 and their new uses
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A technology for compounds and uses, applied in the field of compounds targeting the actin-binding protein Transgelin-2, can solve problems such as undiscovered activity, and achieve the effect of broad application prospects
Active Publication Date: 2019-07-26
SHANGHAI UNIV OF T C M +1
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[0005] N-[(4-{[(1Z)-8-methoxy-4,4-dimethyl-4,5-dihydro-1H-[1,2]dithiolo[3,4-c]quinolin-1-ylidene]amino }phenyl)sulfonyl]acetamide compound (CID 1896138), there is no research report on its activity in the world
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Embodiment 1
[0040] Example 1 The biomolecular interaction analysis experiment proves that the compound (CID 1896138) is effectively combined with Transgelin2
[0045] Turn on the machine, replace it with HBS-EP buffer, insert the chip, and use HBS-EP buffer to flush the pipeline, injection pump, and microfluidic control system (IFC) at high speed. And use 70% glycerol for normalization so that all channels have the same signal.
[0046] 1.2 Chip Surface Pretreatment
[0047] The PI of Transgelin2 protein is 8.98866, the concentration is 1.5mg / mL, and the molecular weight is 23694.9.
[0048] According to the basic information of Transgelin2, pH=5.71, 10mM sodium acetate solution was selected to dilute the protein ...
Embodiment 2
[0058] Example 2 Detection of compound (CID 1896138) anti-contraction ability of smooth muscle cells by real-time label-free cell analysis technique (RTCA)
[0059] 1. Experimental materials
[0060] 1.1. Experimental subjects
[0061] Rat airway smooth muscle cells
[0062] 1.2. Experimental Instruments
[0063] xCELLigence cell function analyzer, E-Plate detection plate, ultra-clean bench, CO 2 Incubator, low-speed centrifuge, pipette, cell counting plate, inverted microscope, mixed gas cylinder (95% O 2 , 5% CO 2 )
[0064] 2. Experimental process
[0065] The subculture of rat airway smooth muscle cells can be subcultured after the cell growth reaches 80% confluence, the culture medium is sucked off, and the cell surface is washed 3 times with D-Hanks solution. Discard the cleaning solution, add 0.25% trypsin solution, place in a 37°C incubator for 3-5 minutes, observe the cell morphology under an inverted microscope, it can be seen that the cells shrink into sheets...
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Abstract
The invention relates to the field of medicine research and development and particularly discloses a compound targeted to actin binding protein Transgelin-2 and new application thereof. Tests reveal that, for the first time, the compound shown in the formula (I) can be effectively targeted to actin binding protein Transgelin-2, has the obvious diastolic function on airway smooth muscle cells, can be used for preparing medicine for airway smooth muscle diastole, can also be used for preparing an airway smooth muscle diastolic agent, and has the wide application prospect.
Description
technical field [0001] The invention relates to the field of drug research and development, and specifically discloses a compound targeting actin-binding protein Transgelin-2 and its new application. Background technique [0002] Hypercontraction of airway smooth muscle is one of the pathological foundations of asthma, and repeated and continuous contraction and spasm of airway smooth muscle in asthmatic patients can lead to proliferation and hypertrophy of smooth muscle cells, and can lead to organic lesions of airway wall thickening. The most widely used clinical beta 2 Adrenergic receptor agonists, as drugs to control acute exacerbations of asthma, also relieve symptoms by relaxing airway smooth muscle cells. [0003] Actin-binding protein 2 (Transgelin-2) was first discovered in 1998. Its gene is located on chromosome 1q21-q25, and its protein expression is located in the cell membrane, actin microfilament, cytoplasm and other parts, including a calmodulin The homology...
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