Application of compound in preparation of medicine for treating tumor cachexia disease

Abstract

The invention discloses an application of a compound or a pharmaceutical salt thereof in preparation of a medicine for preventing or treating tumor cachexia diseases. The structure of the compound is shown in the specification. The result of the embodiment of the invention shows that the compound provided by the invention can inhibit skeletal muscle atrophy so as to treat or improve tumor cachexia.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically, it relates to the use of a compound in the preparation of a drug for treating tumor cachexia. Background Technology

[0002] Cachexia is a wasting syndrome caused by multiple factors, including tumors or other chronic diseases such as injury, organ failure, sepsis, rheumatoid arthritis, and HIV / AIDS, accompanied by weight loss and imbalances in energy and protein metabolism. The occurrence of this syndrome involves systemic inflammatory responses, increased oxidative stress, and abnormal activation of protein degradation pathways, represented by the ubiquitin-protease system, ultimately leading to catabolism far exceeding anabolism.

[0003] Among numerous contributing factors, tumors are the leading cause of cachexia. The interaction between the tumor and the body produces excessive inflammatory cytokines, triggering widespread oxidative stress and activation of the ubiquitination protein degradation system. This increases protein catabolism and decreases anabolism, leading to severe weight loss and muscle atrophy. Cachexia not only reduces patients' quality of life and shortens their survival time but also severely impacts the implementation of treatment plans for underlying diseases, reduces drug sensitivity, and increases the incidence of complications. Current standard treatments for tumor cachexia include nutritional support and appetite stimulants (medroxyprogesterone acetate and medroxyprogesterone acetate), but these are not effective in preventing weight loss and skeletal muscle atrophy.

[0004] The persistent weight loss caused by cancer cachexia is primarily due to skeletal muscle atrophy. The mechanism of skeletal muscle atrophy is highly complex, involving excessive production of inflammatory cytokines and hormonal imbalances. This activates catabolic signaling pathways, primarily JAK-STAT3, SMAD-FOXO, and NF-κB, leading to the activation of the ubiquitin-protease system—a major protein degradation pathway—mediating protein degradation and skeletal muscle atrophy. Increasing evidence suggests that activation of signal transducer and activator of transcription 3 (STAT3) is associated with cachexia induced by various diseases. Studies have shown that STAT3 activates myostatin and the ubiquitin-protease system by regulating CAAT / enhancer-binding protein δ (C / EBPδ), ultimately activating the protein degradation pathway and leading to muscle atrophy.

[0005] Inhibiting skeletal muscle atrophy is an important approach to preventing and treating cancer cachexia. Currently, drugs for treating skeletal muscle atrophy caused by cancer cachexia mainly include natural products, β-adrenergic receptor agonists, enzyme inhibitors, and antibodies. STAT3 is an important target for preventing and treating cancer cachexia. Current research has found that the small molecule inhibitor C188-9 of STAT3 can reverse muscle wasting in colon cancer cells CT26 and lung cancer cells LLC tumor mice by increasing muscle protein synthesis and inhibiting protein degradation. Furthermore, it has been reported that treatment of C2C12 myotubes with cell-permeable STAT3 SH2 domain mimic peptides (SIPs) can induce myofibril hypertrophy and inhibit IL-6-induced myofibril atrophy. A phase II clinical trial showed that the STAT3 upstream kinase Jak1 / 2 inhibitor Ruxolitinib significantly increased the body weight of pancreatic cancer patients. These findings indicate that STAT3 is an effective target for the treatment of cancer cachexia, and the development of new STAT3 inhibitors has potential application value in the treatment of cancer cachexia. Summary of the Invention

[0006] The purpose of this invention is to provide the use of a compound in the preparation of a medicament for treating tumor cachexia.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0008] In a first aspect, the present invention provides the use of a compound or a pharmaceutical salt thereof in the preparation of a medicament for the prevention or treatment of tumor cachexia, the structure of said compound being shown below:

[0009] .

[0010] The compound, CAS number 53947-92-5, was purchased from Chengdu Ruifenside Biotechnology Co., Ltd.

[0011] The aforementioned tumor cachexia includes weight loss caused by tumor tissue, muscle atrophy caused by tumor tissue, cardiac atrophy caused by tumor tissue, anorexia caused by tumor tissue, loss of skeletal muscle mass caused by tumor tissue, and decreased fat storage caused by tumor tissue, as well as tumor cachexia caused by gastric cancer, esophageal cancer, liver cancer, lung cancer, colon cancer, etc.

[0012] The drug for preventing or treating tumor cachexia uses the compound or its pharmaceutical salt as the sole active ingredient.

[0013] The drug for preventing or treating cancer cachexia is made from the compound or its pharmaceutical salt and medically acceptable excipients.

[0014] The drugs mentioned for the prevention or treatment of tumor cachexia are suspensions, granules, capsules, tablets, powders, emulsions, solutions, pellets, injections, suppositories, enemas, aerosols, patches, or drops.

[0015] The administration methods for the drugs used to prevent or treat tumor cachexia include oral administration, intravenous administration, intraperitoneal injection, intramuscular injection, subcutaneous injection, sublingual administration, transdermal administration, or rectal suppository administration.

[0016] The drug for preventing or treating cancer cachexia is made from the compound or its pharmaceutical salt and other drugs for treating cancer cachexia.

[0017] The drug for preventing or treating tumor cachexia is a pharmaceutical composition comprising the compound or its pharmaceutical salt or derivative thereof.

[0018] The compound can inhibit skeletal muscle atrophy and thus play a role in treating or improving tumor cachexia.

[0019] A second aspect of the present invention provides the use of a compound or a pharmaceutical salt thereof in the preparation of a medicament for the prevention or treatment of skeletal muscle atrophy.

[0020] The drugs mentioned for the prevention or treatment of skeletal muscle atrophy are those that specifically bind to the STAT3 protein.

[0021] The drugs mentioned for the prevention or treatment of skeletal muscle atrophy are those that inhibit the activation of the STAT3 protein.

[0022] The drugs mentioned for the prevention or treatment of skeletal muscle atrophy are those that inhibit the expression of E3 ubiquitination ligases MuRF1 and Atrogin-1 proteins and mRNA.

[0023] By adopting the above technical solution, the present invention has the following advantages and beneficial effects:

[0024] The compounds provided by this invention can inhibit skeletal muscle atrophy, thereby treating or improving tumor cachexia.

[0025] This invention is the first to discover that the compound Corylin, with CAS number 53947-92-5, can specifically bind to STAT3 and inhibit its transcriptional activity. At the cellular level, it can significantly inhibit myotube atrophy induced by tumor cell supernatant and inhibit the expression of E3 ubiquitin ligases MuRF1 and Atrogin-1, key molecules in skeletal muscle catabolism. At the whole animal level, it can significantly inhibit weight loss, tibialis anterior muscle, gastrocnemius muscle, and epididymal fat loss in cachexia model mice. At the same time, it can inhibit the expression of MuRF1 and Atrogin-1 in muscle tissue and improve cachexia symptoms.

[0026] Corylin is a flavonoid active ingredient isolated from the dried, mature fruit of the legume *Psoralea corylifolia* L. This invention demonstrates that the compound Corylin can inhibit the transcriptional activation and phosphorylation of STAT3 induced by IL-6 or tumor-conditioned medium (TCM). Simultaneously, it can inhibit the expression of key protein degradation enzymes and alleviate TCM-induced myotube atrophy. Furthermore, the study found that Corylin has a therapeutic effect on CT26-induced cachexia in Balb / c mice, significantly improving various cachexia disease characteristics. Attached Figure Description

[0027] Figure 1 This is a schematic diagram showing the binding characteristics of the compound Corylin with STAT3 as analyzed by SPR.

[0028] Figure 2 This is a schematic diagram showing the results of molecular simulation docking analysis of the binding between compound Corylin and STAT3.

[0029] Figure 3 This is a schematic diagram showing the inhibitory effect of the compound Corylin on STAT3 transcription levels.

[0030] Figure 4 This is a schematic diagram showing the inhibitory effect of the compound Corylin on STAT3 protein activation induced by CT26 cell supernatant.

[0031] Figure 5 This is a schematic diagram showing the protective effect of the compound Corylin against C2C12 myotube atrophy induced by CT26 cell supernatant.

[0032] Figure 6 This is a schematic diagram showing the inhibitory effect of the compound Corylin on the expression of E3 ubiquitin ligases MuRF1 and Atrogin-1 protein and mRNA in C2C12 myotube atrophy induced by CT26 cell supernatant.

[0033] Figure 7 This is a schematic diagram showing the effects of the compound Corylin on reversing weight loss, tibialis anterior muscle, gastrocnemius muscle, and epididymal fat loss and muscle degradation in a CT26 tumor-induced cachexia model in mice.

[0034] Figure 8 This is a schematic diagram showing the pathological results of the inhibitory effect of the compound Corylin on muscle fiber atrophy in the gastrocnemius muscle tissue of mice in a CT26 tumor-induced cachexia model.

[0035] Figure 9This is a schematic diagram showing the inhibitory effect of the compound Corylin on the expression of E3 ubiquitin ligases MuRF1 and Atrogin-1 protein and mRNA in mouse skeletal muscle in a CT26 tumor-induced cachexia model. Detailed Implementation

[0036] To more clearly illustrate the present invention, the following description, in conjunction with preferred embodiments, further clarifies the invention. Those skilled in the art should understand that the specific descriptions below are illustrative rather than restrictive, and should not be construed as limiting the scope of protection of the present invention.

[0037] The structures of the compounds used in the embodiments of this invention are shown below:

[0038]

[0039] CAS No. 53947-92-5, purchased from Chengdu Ruifenside Biotechnology Co., Ltd., abbreviated as Corylin.

[0040] Example 1

[0041] The interaction mode between compound Corylin and STAT3 was analyzed using surface plasmon resonance (SPR). The specific method is as follows:

[0042] The isoelectric point of STAT3 protein was calculated to be pH 6.34. STAT3 protein was diluted to a final concentration of 20 μg / ml using acetate buffers with concentrations of 10 mM and pH values ​​of 4.0, 4.5, 5.0, and 5.5, respectively. The diluted buffers were then passed through the chip surface. The buffer with pH 4.0, which yielded the maximum response value (RU), was selected as the optimal coating buffer.

[0043] STAT3 was coupled to the FC2 channel of the CM5 chip using an amino-coupled method: STAT3 protein was diluted to a final concentration of 10 μg / ml with 10 mM pH 4.0 acetate buffer. The chip surface was treated with a 1:1 mixture of 0.2 M EDC and 50 mM NHS at a flow rate of 10 μl / min for 7 min, followed by injection of the protein solution. After 10 min, 1 M ethanolamine at pH 8.5 was injected to block the activating groups on the chip surface, and the treatment was incubated overnight. Kinetic experiments were performed by injecting prepared compound sample solutions (0, 0.125, 0.25, 0.5, 1, 2, 4, 8, 16 µM) at a flow rate of 30 μl / min for 60 s, followed by a 120 s dissociation period. Data were analyzed using a 1:1 kinetic model or a stable binding model in the Biacore T200 evaluation software. Results are shown below. Figure 1As shown, Figure 1 This is a schematic diagram showing the binding characteristics of compound Corylin with STAT3 as analyzed by SPR. The diagram shows that Corylin specifically binds to STAT3, with a binding dissociation constant Kd = 1.78 µM.

[0044] Example 2

[0045] Molecular simulation docking analysis was performed to analyze the binding of compound Corylin to STAT3. The specific method is as follows:

[0046] Molecular docking was performed using the CDOCKER module in Discovery Studio 3.0. The protein structure, numbered 1BG1, was downloaded from the PDB database, and the DNA strand and water molecules were removed. After applying a CHARMM force field to the molecules to be docked, they were placed at docking sites. Top hits, Random conformation, and Orientations to refine were all set to 10, with all other settings left at default. The CDOCKER ENERGY algorithm was calculated to evaluate the optimal conformation, and the docking results were processed using PYMOL. The results are shown below. Figure 2 As shown, Figure 2 This is a schematic diagram illustrating the binding results of compound Corylin with STAT3 in molecular simulation docking analysis. The diagram shows that Corylin can bind to the STAT3 protein, form hydrogen bonds with Arg609, Ser611, and Ser613, and form a Pi-Pi interaction with Lys-591, with a binding energy of -10.73 kJ / mol.

[0047] Example 3

[0048] The reporter gene assay was used to detect the inhibitory effect of the compound Corylin on STAT3 transcriptional activity. The specific method is as follows:

[0049] The Hela-STAT3-luc cell line, a reporter gene stably expressing STAT3-luciferrase, was constructed by Shanghai Jimon Biotechnology Co., Ltd. This cell line was then used at a rate of 1×10⁻⁶ cells / year. 4Cells were seeded at a density of 100 cells / well in 96-well plates. The following day, 25 ng of TK-Renilla plasmid was transfected with Fugene HD (Promega) as an internal control. 24 h after transfection, cells were pretreated with different concentrations of Corylin for 2 h, followed by co-incubation with IL-6 (100 ng / ml) and IL-6R (100 ng / ml) for 24 h. Fluorescence values ​​were detected using the Dual-Luciferase Reporter Assay System (Promega) to investigate the effect of Corylin on STAT3 transcriptional activity. Results are as follows: Figure 3 As shown, Figure 3 This diagram illustrates the inhibitory effect of the compound Corylin on STAT3 transcription. As can be seen from the figure, Corylin can dose-dependently inhibit STAT3 transcriptional activity at concentrations of 5–20 µm.

[0050] Example 4

[0051] The inhibitory effect of the compound Corylin on STAT3 protein phosphorylation was detected by Western blot, and the specific method is as follows:

[0052] Mouse colon adenocarcinoma cells CT26 were cultured in DMEM medium containing 10% FBS. When the cell confluence reached about 90%, the medium was replaced with DMEM medium containing 2% horse serum and cultured for another 36 h. The supernatant of the cultured CT26 cells was collected and centrifuged at 4500 rpm for 5 min at 4℃. The obtained CT26 supernatant was diluted in differentiation medium at a volume ratio of 1:4 as a myotube atrophy stimulant.

[0053] Mouse myoblast cell line C2C12 was used at 2×10 5 Cells were seeded at a density of 100 cells / well in 6-well plates and induced with 2% horse serum for 3 days to differentiate into myotube cells. After differentiation, the cells were pre-incubated with different concentrations of Corylin for 2 hours, followed by stimulation with diluted CT26 cell supernatant for 24 hours. Cells were then lysed, and the protein expression of p-STAT3 and STAT3 was detected by Western blot. Results are shown below. Figure 4 As shown, Figure 4 This diagram illustrates the inhibitory effect of the compound Corylin on STAT3 protein activation induced by CT26 cell supernatant. The figure shows that Corylin at concentrations of 10 µM and 20 µM significantly inhibited STAT3 protein phosphorylation.

[0054] Example 5

[0055] The protective effect of the compound Corylin against C2C12 myotube atrophy induced by CT26 cell supernatant was observed using immunofluorescence staining. The specific method is as follows:

[0056] Mouse myoblast cell line C2C12 was used at 2×10 5 Cells were seeded at a density of 10 cells / well in 24-well plates and induced to differentiate into multinucleated myotubules for 3 days with 2% horse serum. The cells were pre-incubated with different concentrations of Corylin (5, 10, 20 µM) for 2 h, followed by induction with diluted CT26 cell supernatant for 72 h. Myotubule atrophy was observed using MyHC immunofluorescence staining, and images were acquired and Diameter distribution curves were plotted under a fluorescence microscope. Results are shown below. Figure 5 As shown, Figure 5 This diagram illustrates the protective effect of compound Corylin against C2C12 myotube atrophy induced by CT26 cell supernatant. Figure A shows the effect of Corylin on myotube atrophy induced by CT26 cell supernatant and the drug's action. The figure shows that after 72 hours of induction with CT26 cell supernatant, the myotube morphology changed significantly, with a decrease in diameter. Treatment with different concentrations of Corylin significantly protected against myotube atrophy. Figure B shows the statistical results of myotube width in each group. The statistical data shows that Corylin significantly improved C2C12 myotube atrophy induced by CT26 cell supernatant.

[0057] Example 6

[0058] The inhibitory effect of compound Corylin on protein ubiquitination degradation in an in vitro muscle atrophy model was detected by Western blot and real-time PCR. The specific methods are as follows:

[0059] Mouse myoblast C2C12 cells at 2×10 5 Cells were seeded at a density of 10 cells / well in 6-well plates and induced to differentiate into multinucleated myotubules with 2% horse serum. Cells were pre-incubated with different concentrations of Corylin (5, 10, 20 µM) for 2 h, followed by induction with diluted CT26 cell supernatant for 48 h. Cells were lysed to extract total protein and RNA. Western blot and real-time PCR were used to detect the expression of MuRF-1 and Atrogin-1 proteins and mRNA. Results are shown below. Figure 6 As shown, Figure 6This diagram illustrates the inhibitory effect of compound Corylin on the protein and mRNA expression of E3 ubiquitin ligases MuRF1 and Atrogin-1 in CT26 cell supernatant-induced C2C12 myotube atrophy. Figure A shows the expression levels of MuRF-1 and Atrogin-1 proteins, demonstrating that Corylin inhibits TCM-induced MuRF-1 and Atrogin-1 protein expression in a concentration-dependent manner. Figure B shows the mRNA expression levels of Atrogin-1 (left) and MuRF1 (right), demonstrating that Corylin inhibits the mRNA expression levels of MuRF-1 and Atrogin-1 in a concentration-dependent manner.

[0060] Example 7

[0061] The study investigated the effect of the compound Corylin on reversing weight and muscle mass loss and muscle degradation in a CT26 tumor-induced cachexia skeletal muscle atrophy model in mice. The specific methods are as follows:

[0062] Mouse CT26 colon adenocarcinoma cells were cultured to passage 4, and the cells were collected and resuspended in PBS buffer at a concentration of 1×10⁶ cells / mL. 7 Cells / ml: 0.2 ml of cell suspension was subcutaneously injected into the dorsal side of the right forelimb of each Balb / c mouse. Starting on day 11 after CT26 cell inoculation, mice were administered Corylin at concentrations of 30 mg / kg and 60 mg / kg via gavage, respectively. The control group received an equal volume of physiological saline via gavage. This was administered once daily for 10 days. Mice were weighed every other day after inoculation. Obvious tumors were visible on day 10, and the length and width of the tumors were measured every other day to calculate tumor weight. Mice were sacrificed around day 21, and epididymal fat, gastrocnemius muscle, and tibialis anterior muscle were harvested and weighed. Results are shown below. Figure 7 As shown, Figure 7This diagram illustrates the reversal effects of the compound Corylin on weight loss, tibialis anterior muscle, gastrocnemius muscle, and epididymal fat loss and muscle degradation in a CT26 tumor-induced cachexia model in mice. A shows the weight of mice after tumor removal in each group, indicating a significant increase in weight compared to the model group. B shows a comparison of hind limb muscle tissue in each group, showing significant muscle atrophy in the model group compared to the control group, while the muscle content in the treatment group is significantly increased compared to the model group. C shows a comparison of tibialis anterior muscle tissue (top) and its mass (bottom), indicating a significant decrease in size and mass in the model group compared to the treatment group. D shows a comparison of epididymal fat tissue (top) and its mass (bottom), indicating a significant decrease in epididymal fat content in the model group compared to the treatment group (60...). The epididymal fat content of mice in the mg / kg group was significantly higher than that in the model group; E is a schematic diagram of the comparison of gastrocnemius muscle tissue in each group (top figure) and the statistical results of gastrocnemius muscle mass (bottom figure). As can be seen from the figure, the size and mass of gastrocnemius muscle in the model group mice were significantly reduced, while the size and mass of gastrocnemius muscle in the drug-treated group mice were significantly increased compared with the model group.

[0063] Part of the gastrocnemius muscle was prepared into paraffin blocks and stained with hematoxylin and eosin (HE). The remaining tissue was flash-frozen in liquid nitrogen and then transferred to a freezer at -80°C for storage. Results are shown below. Figure 8 As shown, Figure 8 This is a schematic diagram illustrating the pathological results of the inhibitory effect of the compound Corylin on gastrocnemius muscle fiber atrophy in a CT26 tumor-induced cachexia model in mice. In Figure A, the diagram shows the HE staining results of gastrocnemius muscle tissue sections from each group of mice. It can be seen that the size and cross-sectional area of ​​gastrocnemius muscle fibers in the model group were significantly reduced, while the size and cross-sectional area of ​​gastrocnemius muscle fibers in the drug-treated group were significantly improved compared to the model group. Figure B shows the statistical results of the cross-sectional area of ​​gastrocnemius muscle fibers in each group of mice. It can be seen that the cross-sectional area of ​​gastrocnemius muscle fibers in the model group was significantly reduced, while the cross-sectional area of ​​gastrocnemius muscle fibers in the drug-treated group was significantly increased compared to the model group.

[0064] In summary, CT26 tumors cause tumor cachexia symptoms. Data show that treatment with the compound Corylin effectively improved the weight loss, skeletal muscle atrophy, and fat loss induced by CT26 tumors in mice. HE staining revealed pathological changes in the gastrocnemius muscle, indicating that Corylin treatment significantly increased the reduced muscle cross-sectional area and improved skeletal muscle atrophy in cachectic mice.

[0065] Real-time PCR and Western blot were used to detect the expression of MuRF-1 and Atrogin-1 mRNA and protein in gastrocnemius muscle. Results are shown below. Figure 9 As shown, Figure 9 This diagram illustrates the inhibitory effect of the compound Corylin on the expression of E3 ubiquitin ligases MuRF1 and Atrogin-1 proteins and mRNAs in mouse skeletal muscle in a CT26 tumor-induced cachexia model. Figure A shows the protein expression of p-STAT3, STAT3, MuRF1, and Atrogin-1 in the gastrocnemius muscle of mice in each group. The figure shows that the expression levels of p-STAT3, MuRF1, and Atrogin-1 in the gastrocnemius muscle tissue of the model group mice were significantly increased, while the expression levels of these proteins in the drug-treated groups were significantly lower than those in the model group. Figure B shows the statistical results of the mRNA expression levels of MuRF1 (right figure) and Atrogin-1 (left figure) in the gastrocnemius muscle of mice in each group. The figure shows that the mRNA expression levels of MuRF1 and Atrogin-1 in the gastrocnemius muscle tissue of mice in the model group mice were significantly increased, while the mRNA expression levels of these proteins in the drug-treated groups were significantly lower than those in the model group. In summary, the expression of MuRF-1 and Atrogin-1 was significantly upregulated in the muscle of CT26 tumor-bearing mice, and treatment with the compound Corylin simultaneously reduced the mRNA and protein expression levels of both MuRF-1 and Atrogin-1. Western blot analysis of p-STAT3 expression in mouse muscle revealed highly activated STAT3 in the CT26 tumor cachexia group, and treatment with the compound Corylin significantly inhibited p-STAT3 levels.

[0066] As can be seen from the above data, the compound provided by the present invention can treat or improve tumor cachexia by inhibiting skeletal muscle atrophy.

[0067] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-described technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes, and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. Use of a compound or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the prevention or treatment of cachexia associated with a neoplasm, characterized in that, The structure of the compound is shown below: ； The CAS number of the compound is 53947-92-5.

2. Use of a compound or a pharmaceutically acceptable salt thereof according to claim 1 for the manufacture of a medicament for the prophylaxis or treatment of cachexia associated with neoplasms, characterized in that, The tumor cachexia includes body weight loss caused by tumor tissue, muscle atrophy caused by tumor tissue, cardiac atrophy caused by tumor tissue, anorexia caused by tumor tissue, tumor cachexia caused by gastric cancer, esophageal cancer, liver cancer, lung cancer, colon cancer.

3. Use of a compound or a pharmaceutically acceptable salt thereof according to claim 1 for the manufacture of a medicament for the prophylaxis or treatment of cachexia associated with neoplasms, characterized in that, The medicine for preventing or treating tumor cachexia disease is taken as the only active ingredient of the compound or its pharmaceutical salt.

4. Use of a compound or a pharmaceutically acceptable salt thereof according to claim 1 for the manufacture of a medicament for the prophylaxis or treatment of cachexia associated with neoplasms, characterized in that, The medicine for preventing or treating tumor cachexia disease is made of the compound or its pharmaceutical salt and a medically acceptable auxiliary material.

5. Use of a compound or a pharmaceutically acceptable salt thereof according to claim 1 for the manufacture of a medicament for the prophylaxis or treatment of cachexia associated with neoplasms, characterized in that, The medicine for preventing or treating tumor cachexia disease is a suspension, granules, capsules, tablets, powders, emulsions, solutions, dripping pills, injections, suppositories, enemas, aerosols, patches or drops.

6. Use of a compound or a pharmaceutically acceptable salt thereof according to claim 1 for the manufacture of a medicament for the prophylaxis or treatment of cachexia associated with neoplasms, characterized in that, The administration mode of the medicine for preventing or treating tumor cachexia disease is oral administration, intravenous administration, intraperitoneal injection, intramuscular injection, subcutaneous injection, sublingual administration, transdermal administration or rectal suppository administration.

7. Use of a compound or a pharmaceutically acceptable salt thereof according to claim 1 for the manufacture of a medicament for the prophylaxis or treatment of cachexia associated with neoplasms, characterized in that, The medicine for preventing or treating tumor cachexia disease is made of the compound or its pharmaceutical salt and other medicines for treating tumor cachexia disease.

8. Use of a compound or a pharmaceutically acceptable salt thereof according to claim 1 for the manufacture of a medicament for the prophylaxis or treatment of cachexia associated with neoplasms, characterized in that, The medicine for preventing or treating tumor cachexia disease is a pharmaceutical composition containing the compound or its pharmaceutical salt or its derivative.

9. Use of a compound or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for preventing or treating skeletal muscle atrophy, characterized in that, The structure of the compound is shown below: ； The CAS number of the compound is 53947-92-5.

10. Use of a compound or a pharmaceutically acceptable salt thereof according to claim 9 for the manufacture of a medicament for preventing or treating skeletal muscle atrophy, characterized in that, The medicine for preventing or treating skeletal muscle atrophy is a medicine specifically binding to STAT3 protein; Or, the medicine for preventing or treating skeletal muscle atrophy is a medicine inhibiting the activation of STAT3 protein; Or, the medicine for preventing or treating skeletal muscle atrophy is a medicine inhibiting the expression amount of E3 ubiquitin ligase MuRF1 and Atrogin-1 protein and mRNA.

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