STAT3 inhibitor and application thereof

A technology of inhibitors and drugs, applied in the direction of organic chemistry, drug combination, antineoplastic drugs, etc., can solve the problems of increasing complications, reducing drug sensitivity, preventing weight loss and skeletal muscle atrophy, etc., to improve bone The effect of muscle atrophy

Active Publication Date: 2020-05-29
SHANGHAI SIXTH PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The occurrence of cachexia not only reduces the quality of life of patients and shortens the survival period of patients, but also seriously affects the implementation of the treatment plan for patients' basic diseases, such as reducing the sensitivity of drug treatment and increasing the occurrence of complications
Current conventional treatments for cancer cachexia include nutritional support and appetite-increasing drugs (megestrol and medroxyprogesterone), but they do not prevent weight loss and skeletal muscle atrophy

Method used

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  • STAT3 inhibitor and application thereof
  • STAT3 inhibitor and application thereof
  • STAT3 inhibitor and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] The present embodiment provides the separation and purification method of IMP, comprising the following steps:

[0045] Step 1, crushing 10.0 kg of Angelica dahurica through a 20-mesh sieve, then adding 6-10 times the amount of 60-75% ethanol to soak, and percolating at a speed of 4-6m L / (min·kg) to obtain the extract;

[0046] In step 2, the extract obtained in step 1 is concentrated under reduced pressure at 80° C. to a relative density of 1.25-1.30 to obtain an extract containing the STAT3 inhibitor;

[0047] In step 3, the extract obtained in step 2 is separated by high performance liquid chromatography, the separation conditions are acetonitrile:water 65:35, the wavelength is 300nm, and the flow rate is 1.2 mg / mL. The result obtained is as figure 1 As shown, the content of IMP was 1.5 mg / g.

[0048] Step 4, adopt the NMR method based on 1H and 13C to the IMP that separation and purification obtains to obtain NMR collection of collections (as figure 2 and imag...

Embodiment 2

[0050] This embodiment provides the application of IMP in the preparation of a drug for treating tumor cachexia, and the drug includes one or more of the IMP, isomers of IMP, pharmaceutically acceptable hydrates, solvates, and salts of IMP.

[0051] In addition, the medicine also includes a pharmaceutically acceptable carrier, selected from any one or more of the following: fillers, binders, solubilizers, disintegrants and glidants.

[0052] The dosage form of the medicine is selected from any one of the following: capsules, tablets, granules, powders, pills or injections.

[0053] Verify Example 1

[0054] This verification example adopts surface plasmon resonance (surface plasmon resonance, SPR) technology to analyze the interaction mode of IMP and STAT3, and the specific method is as follows:

[0055] 1. Calculate the isoelectric point of STAT3 protein as pH 6.34, choose 10mmol / L acetate buffer with pH 4.0, 4.5, 5.0 and 5.5 to dilute the coupled protein STAT3 to a final co...

Embodiment 3

[0066] This verification example is to study the inhibitory effect of IMP on the activation of STAT3 protein in vitro, and the specific method is as follows:

[0067] At present, there are many in vitro models of cachexia skeletal muscle atrophy, mainly including tumor cell culture supernatant, dexamethasone, TNF-α, IFN-γ, IL-6 and chemotherapy drugs, etc. can be used as in vitro inducers to induce C2C12 myotube atrophy. Among them, the tumor cell culture supernatant can best simulate the tumor cachexia environment in vivo, so in subsequent experiments, the tumor cell culture supernatant (TCM) was used as the inducer of the in vitro model of skeletal muscle atrophy. CT26 is a colon adenocarcinoma cell derived from mice. It was cultured in 100 μL DMEM complete medium containing 10% FBS. When the cell confluency reached about 90%, it was replaced with DMEM medium containing 2% horse serum. The culture was continued for 36 hours, and the culture was collected. The supernatant of ...

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Abstract

The invention relates to the technical field of biology, and discloses an STAT3 inhibitor and an application thereof. The structure of the STAT3 inhibitor is shown as S-I (See the specification for reference). The invention provides an application of the STAT3 inhibitor in preparation of a medicine for treating tumor cachexia. The STAT3 inhibitor provided by the invention is simple in separation and purification method, can inhibit STAT3 activation and further improve skeletal muscle atrophy, and provides a new strategy for preparing drugs for treating or improving tumor cachexia.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a STAT3 inhibitor and application thereof. Background technique [0002] Cachexia is a wasting syndrome caused by multiple factors such as tumor or other chronic diseases including injury, organ failure, sepsis, rheumatoid arthritis and HIV / AIDS, accompanied by weight loss and energy and protein metabolism imbalance . Tumor cachexia——as the primary factor of cachexia, excessive inflammatory cytokines are produced through the interaction between the tumor and the body, causing extensive oxidative stress response and activation of the ubiquitin protein degradation system, increased protein catabolism, and insufficient anabolism, leading to severe weight loss and muscle loss. The occurrence of cachexia not only reduces the quality of life of patients and shortens the survival period of patients, but also seriously affects the implementation of the treatment plan for patients' basic di...

Claims

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Application Information

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IPC IPC(8): C07D493/04A61P35/00
CPCC07D493/04A61P35/00
Inventor 郭澄杨全军陈林林
Owner SHANGHAI SIXTH PEOPLES HOSPITAL
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