Use of sphinx31 in the preparation of a medicament for the treatment and / or prevention of pulmonary fibrosis

Abstract

The application discloses application of SPHINX31 in preparation of drugs for treating and / or preventing pulmonary fibrosis and belongs to the technical field of medicines. The application first finds that SPHINX31 can play an anti-pulmonary fibrosis role by targeting SRPK1 and regulating an SRPK1 / SRSF1 related pathway. Experimental results show that SPHINX31 can reduce the expression of fibrosis related genes such as Col1a1, Acta2 and Fn1 in lung tissues, reduce the content of hydroxyproline, reduce collagen deposition, inhibit the activation of myofibroblasts, and improve the pathological changes of lung tissue structure damage, alveolar septum thickening, inflammatory cell infiltration and fibrosis. The application provides a brand new drug selection for the treatment of pulmonary fibrosis and has the advantages of clear target and remarkable curative effect.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to new pharmaceutical uses of the serine / arginine enriched protein kinase 1 (SRPK1) targeting small molecule compound SPHINX31, and particularly to the use of SPHINX31 or a pharmaceutically acceptable salt thereof in the preparation of drugs for the treatment and / or prevention of pulmonary fibrosis, especially idiopathic pulmonary fibrosis (IPF). Background Technology

[0002] Pulmonary fibrosis is a chronic, progressive lung disease characterized by the destruction of lung tissue structure, abnormal activation of fibroblasts, aggregation of myofibroblasts, and excessive deposition of extracellular matrix. It can be induced by various factors, including environmental dust exposure, drug toxicity, radiation damage, infection, autoimmune diseases, and interstitial lung diseases of unknown cause. Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with an unclear etiology, rapid progression, and poor prognosis. As the disease progresses, the alveolar structure gradually deteriorates, and extracellular matrix such as collagen continues to deposit, ultimately leading to decreased lung compliance, impaired gas exchange, and respiratory failure, seriously threatening the patient's life and health.

[0003] Currently, the clinical treatment of pulmonary fibrosis, especially idiopathic pulmonary fibrosis (IPF), still faces significant challenges. While pirfenidone and nintedanib are approved for IPF treatment and can slow the decline in lung function to some extent, their main effect is to slow disease progression; they are unlikely to reverse existing fibrotic lesions, and some patients experience gastrointestinal reactions, abnormal liver function, and poor treatment tolerance. Therefore, identifying new anti-pulmonary fibrosis targets and small-molecule drug candidates with clear pharmacological bases is crucial for developing more effective treatment strategies for pulmonary fibrosis.

[0004] The development of pulmonary fibrosis involves multiple stages, including repeated damage and abnormal repair of alveolar epithelial cells, persistent inflammatory responses, fibroblast activation, myofibroblast differentiation, and abnormal extracellular matrix deposition. In addition to classic pro-fibrotic transcriptional regulatory pathways, recent studies have shown that post-transcriptional regulation, especially alternative splicing, plays an increasingly important role in fibrotic diseases. Alternative splicing can cause the same gene to produce different transcripts and protein isoforms, thereby affecting various biological processes such as cell proliferation, apoptosis, migration, metabolic reprogramming, and extracellular matrix formation. The abnormal transitions in fibroblast and epithelial cell states during pulmonary fibrosis may be closely related to the abnormal activation of splicing factors and their upstream regulatory kinases.

[0005] Serine / arginine-rich protein-specific kinase 1 (SRPK1) is an important upstream kinase regulating the phosphorylation, subcellular localization, and splicing activity of SR protein family splicing factors. SRPK1 participates in RNA splicing, mRNA export, post-transcriptional regulation, and cell fate determination by regulating the phosphorylation state and functional activity of SRSF family proteins, especially the classical splicing factor SRSF1.

[0006] SPHINX31 is a small molecule compound that targets SRPK1 and has been reported to have a pharmacological basis in inhibiting SRPK1 activity, affecting SRSF1 phosphorylation, and regulating SR protein-related splicing processes. Compared with nucleic acid drugs, cell therapies, or complex biologics, small molecule compounds have advantages such as well-defined structures, relatively convenient preparation and quality control, and clearer drug development pathways. Currently reported research on SPHINX31 mainly focuses on the anti-tumor field (e.g., acquired resistance in non-small cell lung cancer, leukemia cell differentiation, extranodal lymphoma) and the field of neovascular eye diseases (e.g., inhibition of choroidal angiogenesis). No literature or patent reports have yet documented the therapeutic effect of SPHINX31 in pulmonary fibrosis, particularly idiopathic pulmonary fibrosis.

[0007] Therefore, developing new uses for SPHINX31 in the preparation of drugs for the treatment of idiopathic pulmonary fibrosis will not only help expand the indications of known SRPK1-targeting small molecule compounds, but also provide new candidate drugs and treatment strategies for targeted intervention of pulmonary fibrosis. Summary of the Invention

[0008] The purpose of this invention is to overcome the aforementioned deficiencies of the prior art and provide novel pharmaceutical uses of SPHINX31 or a pharmaceutically acceptable salt thereof in the preparation of drugs for the treatment and / or prevention of pulmonary fibrosis. This invention is the first to discover that the small molecule compound SPHINX31, targeting SRPK1, can effectively alleviate bleomycin-induced pulmonary fibrosis in mice, providing a novel drug target and candidate compound for the treatment of pulmonary fibrosis.

[0009] To achieve the objectives of this invention, the following technical solution is adopted: First, this invention provides the use of SPHINX31 or a pharmaceutically acceptable salt thereof in the preparation of medicaments for the treatment and / or prevention of pulmonary fibrosis. The chemical structural formula of SPHINX31 is shown in Formula (I): .

[0010] SPHINX31 (CAS No.: 1818389-84-2) is a known selective small molecule inhibitor of SRPK1, with the chemical name N-(2-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-5-(trifluoromethyl)phenyl)-5-(pyridin-4-yl)furan-2-carboxamide, and the molecular formula C1. 27 H 24 F3N5O2 has a molecular weight of 507.51. SPHINX31 is an ATP-competitive SRPK1 inhibitor. In this invention, the pulmonary fibrosis includes, but is not limited to, idiopathic pulmonary fibrosis, bleomycin-induced pulmonary fibrosis, drug- or toxin-induced pulmonary fibrosis, radiation-induced pulmonary fibrosis, post-infectious lung injury-related pulmonary fibrosis, pneumoconiosis-related pulmonary fibrosis, and interstitial lung disease associated with autoimmune diseases.

[0011] The main pathological features of pulmonary fibrosis include: destruction of lung tissue structure, collagen deposition, fibroblast activation, myofibroblast differentiation, and abnormal accumulation of extracellular matrix.

[0012] Preferably, the drug exerts its anti-pulmonary fibrosis effect by targeting SRPK1 or regulating the SRPK1 / SRSF1-related pathway.

[0013] This study found that in a bleomycin-induced pulmonary fibrosis mouse model, the levels of SRPK1 and SRSF1 proteins in lung tissue were significantly increased; after treatment with SPHINX31, as the pathological changes in pulmonary fibrosis improved, the levels of SRPK1 and SRSF1 proteins decreased accordingly. These results suggest that SPHINX31 can exert its anti-pulmonary fibrosis effect by inhibiting the activation of the SRPK1 / SRSF1 pathway.

[0014] Preferably, the drug reduces the expression of fibrosis-related genes in lung tissue, including one or more of Col1a1 (type I collagen α1 chain), Acta2 (α-smooth muscle actin, α-SMA), and Fn1 (fibronectin 1).

[0015] Preferably, the drug reduces the hydroxyproline (HYP) content in lung tissue, thereby reducing collagen deposition. Hydroxyproline is a specific amino acid of collagen, and its content can quantitatively reflect the degree of collagen deposition in tissues.

[0016] Preferably, the drug reduces positive expression of COL1A1 and / or COL1 protein in lung tissue and inhibits extracellular matrix accumulation.

[0017] Preferably, the drug reduces α-SMA positive expression in lung tissue and inhibits myofibroblast activation. α-SMA is a marker protein of myofibroblasts, and its expression level reflects the degree of differentiation of fibroblasts into myofibroblasts.

[0018] Preferably, the drug reduces and improves pathological changes in lung tissue, including but not limited to reduced damage to lung tissue structure, improved thickening of alveolar septa, reduced infiltration of inflammatory cells, and reduced area of ​​fibrotic lesions.

[0019] Preferably, the dosage of SPHINX31 or a pharmaceutically acceptable salt thereof is a therapeutically effective amount; further, the dosage, based on SPHINX31, is 0.001–1 mg / kg / dose, preferably 0.005–0.5 mg / kg / dose, and even more preferably 0.01–0.2 mg / kg / dose.

[0020] Preferably, the drug further includes pharmaceutically acceptable excipients.

[0021] Preferably, the pharmaceutically acceptable excipients include any one or a combination of at least two of the following: sustained-release agents, excipients, fillers, binders, wetting agents, disintegrants, absorption enhancers, surfactants, lubricants, stabilizers, preservatives, and solubilizers.

[0022] Preferably, the drug dosage form is a tablet, capsule, granule, injection, lyophilized powder for injection, oral liquid, pill, suspension, dispersant, syrup, suppository, gel, aerosol, nebulized inhalation preparation, or pulmonary delivery preparation.

[0023] Preferably, the administration method of the drug includes oral administration, intravenous administration, intraperitoneal injection, subcutaneous injection, intramuscular injection, endotracheal administration, nebulized inhalation administration, or local delivery to the lungs.

[0024] Secondly, the present invention also provides a pharmaceutical composition for treating and / or preventing idiopathic pulmonary fibrosis, comprising SPHINX31 or a pharmaceutically acceptable salt thereof, and pharmaceutically acceptable excipients.

[0025] Preferably, the pharmaceutical composition contains 0.001–99 wt% of SPHINX31 or a pharmaceutically acceptable salt thereof.

[0026] The present invention also provides the use of SPHINX31 or a pharmaceutically acceptable salt thereof in the preparation of reagents for the in vitro inhibition of the expression of one or more fibrosis-related molecules among Col1a1, Acta2, Fn1, COL1A1, COL1 and / or α-SMA, or for the evaluation of SRPK1 / SRSF1-related fibrosis activation processes.

[0027] Compared with the prior art, the present invention has the following beneficial effects: This invention provides a novel use for SPHINX31. Animal experiments have shown that SPHINX31 can significantly alleviate bleomycin-induced pulmonary fibrosis pathological changes in mice under therapeutic intervention. This compound can reduce the expression of fibrosis-related genes such as Col1a1, Acta2, and Fn1 in lung tissue, decrease hydroxyproline content and collagen deposition in lung tissue, and reduce the positive staining area of ​​COL1A1 and α-SMA. These results indicate that SPHINX31 can alleviate lung tissue structural damage, inhibit myofibroblast activation, reduce extracellular matrix deposition, and alleviate the progression of pulmonary fibrosis. It shows promise in the preparation of drugs for the treatment and / or prevention of idiopathic pulmonary fibrosis, providing a new small-molecule therapeutic strategy for the clinical intervention of pulmonary fibrosis, and realizing the development of a new use for SPHINX31. Attached Figure Description

[0028] Figure 1 The experimental design for SPHINX31 treatment of bleomycin-induced pulmonary fibrosis in animal models and the results of mRNA expression detection of pulmonary fibrosis-related genes are shown in Figure 1. A is the animal experimental flowchart; B is the Col1a1 mRNA expression level; C is the Acta2 mRNA expression level; and D is the Fn1 mRNA expression level.

[0029] Figure 2 The results of SPHINX31 in reducing collagen deposition in lung tissue are shown in Figure A, which is a representative image of Masson staining; Figure B is the quantitative analysis result of Masson staining positive area or collagen deposition area; and Figure C is the detection result of hydroxyproline content in lung tissue.

[0030] Figure 3 The results of SPHINX31 improving lung tissue pathological damage in mice are shown in Figure A, where A is a representative image of H&E staining; and B is the lung tissue pathological damage score or pulmonary fibrosis score.

[0031] Figure 4 Immunohistochemical results of SPHINX31 inhibition of myofibroblast activation and extracellular matrix deposition in lung tissue are shown. In Figure A, the upper part is a representative image of Collagen I immunohistochemical staining; the lower part of Figure A is a representative image of α-SMA immunohistochemical staining; the left side of Figure B shows the quantitative analysis results of Collagen I positive staining area; and the right side of Figure B shows the quantitative analysis results of α-SMA positive staining area.

[0032] Figure 5The changes in SRPK1 / SRSF1-related protein levels in lung tissue after bleomycin-induced pulmonary fibrosis and SPHINX31 treatment are shown in Figure A, where SRPK1 protein levels and their quantitative analysis results are represented, and SRSF1 protein levels and their quantitative analysis results are represented in Figure B. Detailed Implementation

[0033] The present invention will now be described in further detail with reference to the accompanying drawings and embodiments, but this does not limit the invention in any way. Any modifications or improvements made based on the teachings of this invention fall within the protection scope of this invention.

[0034] The processes, conditions, reagents, and experimental methods used in implementing this invention, except as specifically mentioned below, are all common knowledge and general knowledge in the field, and this invention does not have any particular limitations. Experimental methods in the embodiments that do not specify specific conditions are generally performed under conventional conditions or according to the manufacturer's recommendations.

[0035] Unless otherwise stated, all technical terms and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. However, in the event of any conflict, the specification containing the definitions shall prevail.

[0036] The following are the sources of some reagents and consumables used in the examples: SPHINX31 was purchased from a commercial reagent company with a purity greater than 95%. Bleomycin sulfate (BLM) for modeling was purchased from a commercial reagent company. C57BL / 6 male mice were purchased from a laboratory animal supplier with a laboratory animal production license. Hydroxyproline detection kit, TRIzol reagent, reverse transcription kit, real-time quantitative PCR reagent, Western blot related reagents, immunohistochemical staining reagents, and histopathological staining reagents were all purchased from routine commercial suppliers in the field.

[0037] Example 1: Therapeutic effect of SPHINX31 in a mouse model of pulmonary fibrosis 1. Experimental modeling, grouping, and drug administration methods The experimental animals were male C57BL / 6 mice, 8 weeks old and weighing approximately 20 g. All animals were housed under specific pathogen-free (SPF) conditions with a 12 h / 12 ​​h day / night light cycle, and the temperature and humidity were maintained within the normal range for experimental animals. They had free access to food and water.

[0038] Mice were randomly assigned to a control group (Saline), a model group (BLM), and a SPHINX31 treatment group (BLM+SPHINX31). The control group received an equal volume of sterile saline intratracheally; the model group and the SPHINX31 treatment group received bleomycin intratracheally at a dose of 1.5 mg / kg to establish a pulmonary fibrosis model. SPHINX31 was prepared as a drug solution using 5% DMSO, 40% PEG300, 5% Tween-80, and 50% saline. Therapeutic drug intervention began on day 7 after modeling. The SPHINX31 treatment group received intraperitoneal injection of SPHINX31 at a dose of 0.8 mg / kg, twice weekly, until day 21 after modeling. The control group and the model group received appropriate solvent treatment. Mice were sacrificed at the experimental endpoint, and lung tissue was collected for subsequent molecular, biochemical, histopathological, and protein expression assays. The experimental flowchart is shown below. Figure 1 A.

[0039] 2. Real-time quantitative PCR detection Lung tissues from mice in each group were collected, and total RNA was extracted using the TRIzol method or an equivalent RNA extraction method. RNA concentration and purity were then measured. Subsequently, the RNA was reverse transcribed into cDNA according to the reverse transcription kit instructions. Real-time quantitative PCR was performed using the SYBR Green assay to detect the genes Col1a1, Acta2, and Fn1, with Gapdh as an internal control gene. The relative expression levels of each target gene were calculated using the 2^-ΔΔCt method to evaluate the regulatory effect of SPHINX31 on the expression of lung fibrosis-related genes.

[0040] 3. Hydroxyproline detection: Lung tissue was collected from each group of mice, accurately weighed, and subjected to alkaline hydrolysis and colorimetric reaction according to the instructions of the hydroxyproline assay kit. Absorbance was measured at 550 nm using an ELISA reader. The hydroxyproline content in lung tissue was calculated based on the absorbance of samples, blanks, and standards, and normalized to the wet weight of lung tissue. Hydroxyproline content was used to evaluate the degree of collagen deposition in lung tissue.

[0041] 4. Masson staining Partial lung tissue was fixed in 4% paraformaldehyde and embedded in paraffin, then serially sectioned with a section thickness of 4 μm. After dewaxing and hydration, the sections were stained according to the Masson staining kit instructions. Following staining, collagen deposition in the lung tissue of each group of mice was observed under an optical microscope, and the Masson-positive area or collagen deposition area was quantitatively analyzed using ImageJ software.

[0042] 5. H&E staining and pathological scoring Partial lung tissue was fixed in 4% paraformaldehyde, then embedded in paraffin and sectioned. After dewaxing and hydration, the sections were stained with Hematoxylin and eosin (H&E). Following staining, the integrity of alveolar structure, alveolar septal thickening, inflammatory cell infiltration, tissue consolidation, and fibrosis-like pathological changes were observed under a light microscope. Based on the H&E staining results, the degree of pathological damage or pulmonary fibrosis in the lung tissue of each group of mice was semi-quantitatively scored to evaluate the ameliorative effect of SPHINX31 on bleomycin-induced lung tissue pathological damage.

[0043] 6. Immunohistochemical detection Paraffin-embedded lung tissue sections were dewaxed, hydrated, and subjected to antigen retrieval, followed by endogenous peroxidase blocking and non-specific blocking. Then, COL1A1 or COL1 primary antibody and α-SMA primary antibody were added, and the sections were incubated overnight at 4°C. The following day, HRP-labeled secondary antibody was added, followed by DAB staining and counterstaining with hematoxylin. Images were acquired under an optical microscope after staining, and the areas of COL1A1 or COL1 positive staining and α-SMA positive staining were quantitatively analyzed using ImageJ software.

[0044] 7. Western blot detection After euthanizing mice at the experimental endpoint, lung tissue was rapidly harvested, and a portion of the lung tissue was flash-frozen in liquid nitrogen for protein detection. The frozen lung tissue was homogenized thoroughly with RIPA lysis buffer, centrifuged, and the supernatant was collected to extract total protein. Protein concentration was determined using the BCA method, and an equal volume of protein sample was added to each well. After separation by SDS-PAGE electrophoresis, the sample was transferred to a PVDF membrane. The membrane was blocked and incubated with the corresponding primary antibodies, including anti-SRPK1 antibody, anti-SRSF1 antibody, and the internal control antibody β-tubulin. Subsequently, HRP-labeled secondary antibody was added for incubation, and ECL chemiluminescence was used for color development. ImageJ software was used for quantitative analysis of the band grayscale values.

[0045] 8. Experimental Results The results of real-time quantitative PCR detection are shown below. Figure 1 BD. The results showed that the expression levels of Col1a1, Acta2, and Fn1 mRNA in the lung tissue of mice in the model group were significantly increased after bleomycin induction, suggesting enhanced collagen deposition, extracellular matrix remodeling, and myofibroblast activation in lung tissue. Compared with the model group, the expression levels of Col1a1, Acta2, and Fn1 in the lung tissue of mice in the SPHINX31 treatment group were significantly decreased, indicating that SPHINX31 can inhibit the expression of bleomycin-induced pulmonary fibrosis-related genes at the molecular level.

[0046] The results of hydroxyproline detection and Masson staining are shown in the figure. Figure 2The results showed that hydroxyproline content in the lung tissue of mice in the model group was significantly increased after bleomycin induction, and a large amount of collagen deposition was observed in Masson staining. Compared with the model group, the hydroxyproline content in the lung tissue of the SPHINX31 treatment group was decreased, and the Masson positive area or collagen deposition area was reduced, suggesting that SPHINX31 can reduce the collagen content in lung tissue and alleviate pulmonary fibrosis-related collagen deposition.

[0047] H&E staining results are shown in […]. Figure 3 The results showed that the lung tissue of mice in the bleomycin model group exhibited significant alveolar structural damage, alveolar septal thickening, inflammatory cell infiltration, and fibrosis-like pathological changes. In contrast, SPHINX31 treatment significantly reduced lung tissue structural damage, relatively improved alveolar structure, and decreased inflammatory cell infiltration and fibrosis. Pathological damage scores or pulmonary fibrosis scores further demonstrated that SPHINX31 could reduce the degree of bleomycin-induced lung tissue pathological damage.

[0048] Immunohistochemical test results are shown in Figure 4 The results showed that in the bleomycin model group, COL1A1 or COL1 positive staining was significantly enhanced in the lung tissue, and the area of ​​α-SMA positive staining was increased, indicating significantly enhanced extracellular matrix deposition and myofibroblast activation. Compared with the model group, the area of ​​COL1A1 or COL1 positive staining and α-SMA positive staining was reduced in the SPHINX31 treatment group, indicating that SPHINX31 can inhibit extracellular matrix accumulation and myofibroblast activation in lung tissue.

[0049] The results of the Western blot analysis are shown below. Figure 5 The results showed that bleomycin-induced SRPK1 and SRSF1 protein levels increased in the lung tissue of mice in the model group; after SPHINX31 treatment, as the pathological changes of pulmonary fibrosis lessened, the relative levels of SRPK1 and SRSF1 proteins decreased. These results suggest that the SRPK1 / SRSF1-related pathway is activated in fibrotic lung tissue, and SPHINX31 treatment can reduce the activation level of the SRPK1 / SRSF1-related pathway in fibrotic lung tissue, possibly exerting an anti-pulmonary fibrosis effect by weakening the fibrosis activation process associated with this pathway.

[0050] In summary, SPHINX31 can reduce the expression of genes related to bleomycin-induced pulmonary fibrosis in mice, decrease hydroxyproline content and collagen deposition, improve pathological damage in lung tissue, and inhibit positive expression of COL1A1 / COL1 and α-SMA. Simultaneously, the elevated levels of SRPK1 and SRSF1 proteins in fibrotic lung tissue decreased after SPHINX31 treatment, suggesting weakened activation of the SRPK1 / SRSF1-related pathway. These results indicate that SPHINX31 can significantly alleviate lung tissue structural damage, inhibit myofibroblast activation, and reduce extracellular matrix deposition, demonstrating potential application value in the preparation of drugs for the treatment and / or prevention of idiopathic pulmonary fibrosis.

[0051] This invention provides a novel pharmaceutical use for the SRPK1-targeting small molecule compound SPHINX31. SPHINX31, as a known selective SRPK1 inhibitor, has a mature chemical synthesis route, well-defined physicochemical properties, and known pharmacokinetic characteristics, providing a good foundation for drug development. This invention, through in vivo experiments, is the first to validate the therapeutic potential of SPHINX31 in pulmonary fibrosis, offering a novel strategy and drug candidate targeting the SRPK1 / SRSF1 pathway for the treatment of pulmonary fibrosis, especially idiopathic pulmonary fibrosis, with clear prospects for clinical translation and industrial application value.

[0052] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. The use of SPHINX31 or a pharmaceutically acceptable salt thereof in the preparation of medicaments for the treatment and / or prevention of pulmonary fibrosis, wherein the chemical structural formula of SPHINX31 is shown in Formula (I): 。 2. The application according to claim 1, characterized in that, The pulmonary fibrosis includes one or more of the following: idiopathic pulmonary fibrosis, bleomycin-induced pulmonary fibrosis, drug- or toxin-induced pulmonary fibrosis, radiation-induced pulmonary fibrosis, post-infectious lung injury-related pulmonary fibrosis, pneumoconiosis-related pulmonary fibrosis, and interstitial lung disease associated with autoimmune diseases.

3. The application according to claim 1, characterized in that, The drug exerts its anti-pulmonary fibrosis effect by targeting SRPK1 and / or regulating the SRPK1 / SRSF1-related pathway.

4. The application according to claim 3, characterized in that, The drug reduces the expression of one or more fibrosis-related genes in Col1a1, Acta2, and Fn1 in lung tissue.

5. The application according to claim 3, characterized in that, The drug reduces the hydroxyproline content in lung tissue and decreases collagen deposition.

6. The application according to claim 3, characterized in that, The drug reduces positive expression of COL1A1 and / or COL1 in lung tissue and inhibits extracellular matrix accumulation.

7. The application according to claim 3, characterized in that, The drug reduces α-SMA positive expression in lung tissue and inhibits myofibroblast activation.

8. The application according to claim 1, characterized in that, The drug improves one or more of the following pathological changes: lung tissue structural damage, alveolar septal thickening, inflammatory cell infiltration, and fibrosis.

9. The application according to any one of claims 1-8, characterized in that, The drug also includes pharmaceutically acceptable excipients.

10. The use of SPHINX31 or a pharmaceutically acceptable salt thereof in the preparation of reagents for the in vitro inhibition of the expression of one or more fibrosis-related molecules, such as Col1a1, Acta2, Fn1, COL1A1, COL1 and / or α-SMA, or for the evaluation of SRPK1 / SRSF1-related fibrosis activation processes.

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