Application of PIM1 kinase inhibitor

Abstract

According to the application of the PIM1 kinase inhibitor, the PIM1 kinase inhibitor participates in cell process regulation through phosphorylation of multiple substrates, the PIM1 kinase inhibitor not only plays a role in an autoimmune disease model, but also can regulate and control neural differentiation and regeneration processes, has the effect of improving intestinal inflammation, and can be used for preparing the PIM1 kinase inhibitor. The PIM1 kinase inhibitor can be used for preparing the medicine for treating and / or preventing the intestinal inflammation, the new possibility of treating and / or preventing the intestinal inflammation is developed, and the PIM1 kinase inhibitor has potential value for treating the intestinal inflammation.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to the application of a PIM1 kinase inhibitor. Background Art

[0002] Intestinal inflammation and mood disorders form a bidirectional association through the "gut-brain axis," a complex communication network that integrates neural, hormonal, and immune pathways. Colonic inflammation may affect central nervous system function by altering synaptic activity, disrupting neuronal signaling, and regulating neuroimmune responses. These interactions are not only involved in the pathogenesis of mood disorders, but may also aggravate the severity and recurrence of intestinal inflammation. Taking ulcerative colitis as an example of intestinal inflammation, ulcerative colitis is a chronic inflammatory disease characterized by diffuse inflammation of the colorectal mucosa. In addition to intestinal symptoms, ulcerative colitis can significantly reduce the quality of life of patients and impose a heavy socioeconomic burden. Among the extraintestinal manifestations of ulcerative colitis, depression and anxiety have become clinical comorbidities that require special attention. Epidemiological studies have shown that more than half of patients in the active phase have symptoms of depression or anxiety.

[0003] Currently, there are limited drugs for treating and / or preventing intestinal inflammation, and their efficacy is relatively ineffective. There is an urgent need to develop new and effective drugs for treating and / or preventing intestinal inflammation. Summary of the Invention

[0004] In view of the shortcomings of the existing technology, the purpose of the present invention is to provide an application of a PIM1 kinase inhibitor. The PIM1 kinase inhibitor can be used to prepare a drug for treating and / or preventing intestinal inflammation, opening up new possibilities for treating and / or preventing intestinal inflammation and having potential value in the treatment of intestinal inflammation.

[0005] In order to achieve the above object, the technical solution adopted by the present invention is as follows: an application of a PIM1 kinase inhibitor, and an application of the PIM1 kinase inhibitor in the preparation of a drug for treating and / or preventing intestinal inflammation.

[0006] In some embodiments, the intestinal inflammation includes one or more of ulcerative colitis, Crohn's disease, infectious enteritis, ischemic enteritis, drug-induced enteritis, radiation enteritis, autoimmune enteritis, and other types of intestinal inflammation.

[0007] In some embodiments, the administration method of the drug for treating and / or preventing intestinal inflammation includes one or more of injection and rectal administration.

[0008] The present application also provides a use of a PIM1 kinase inhibitor, wherein the use of the PIM1 kinase inhibitor is in the preparation of a drug for treating and / or preventing neuropsychiatric comorbidities of intestinal inflammation.

[0009] In some embodiments, the neuropsychiatric comorbidities of intestinal inflammation include one or more of depression and anxiety.

[0010] In some embodiments, the administration method of the drug for treating and / or preventing neuropsychiatric comorbidities of intestinal inflammation includes one or more of injection and rectal administration.

[0011] The present application also provides an application of a PIM1 kinase inhibitor, wherein the application of the PIM1 kinase inhibitor is in the preparation of a drug for treating and / or preventing intestinal inflammation and its neuropsychiatric comorbidities.

[0012] In some embodiments, the intestinal inflammation includes one or more of ulcerative colitis, Crohn's disease, infectious enteritis, ischemic enteritis, drug-induced enteritis, radiation enteritis, autoimmune enteritis, and other types of intestinal inflammation.

[0013] In some embodiments, the neuropsychiatric comorbidities of intestinal inflammation include one or more of depression and anxiety.

[0014] In some embodiments, the administration method of the drug for treating and / or preventing intestinal inflammation and its neuropsychiatric comorbidities includes: one or more of injection administration and rectal administration.

[0015] The application of the PIM1 kinase inhibitor of the present invention involves the regulation of cellular processes by phosphorylating multiple substrates. PIM1 kinase inhibitors not only play a role in autoimmune disease models, but also regulate neural differentiation and regeneration processes, and have the effect of improving intestinal inflammation. Therefore, PIM1 kinase inhibitors can be used to prepare drugs for treating and / or preventing intestinal inflammation, opening up new possibilities for treating and / or preventing intestinal inflammation, and have potential value in the treatment of intestinal inflammation.

[0016] The application of the PIM1 kinase inhibitor of the present invention involves in regulating cellular processes by phosphorylating multiple substrates. PIM1 kinase inhibitors not only play a role in autoimmune disease models, but also regulate neural differentiation and regeneration processes, and have the effect of improving neuropsychiatric comorbidities of intestinal inflammation. Therefore, PIM1 kinase inhibitors can be used to prepare drugs for treating and / or preventing neuropsychiatric comorbidities of intestinal inflammation, opening up new possibilities for treating and / or preventing neuropsychiatric comorbidities of intestinal inflammation, and have potential value in the treatment of neuropsychiatric comorbidities of intestinal inflammation.

[0017] The application of the PIM1 kinase inhibitor of the present invention is that the PIM1 kinase inhibitor participates in the regulation of cellular processes by phosphorylating multiple substrates. The PIM1 kinase inhibitor not only plays a role in autoimmune disease models, but also can regulate neural differentiation and regeneration processes, and has the effect of improving intestinal inflammation and its neuropsychiatric comorbidities. Therefore, the PIM1 kinase inhibitor can be used to prepare drugs for treating and / or preventing intestinal inflammation and its neuropsychiatric comorbidities, opening up new possibilities for treating and / or preventing intestinal inflammation and its neuropsychiatric comorbidities, and has potential value in the treatment of intestinal inflammation and its neuropsychiatric comorbidities.

[0018] Figures in the specification

[0019] Figure 1 Immunofluorescence staining of PIM1 in colon tissue; the left column of the picture represents the control group (control group), and the right column of the picture represents the DSS group (ulcerative colitis group);

[0020] Figure 2 The detection diagram of PIM1 level in mouse plasma; among them, DSS group is ulcerative colitis group, Sham group is sham operation group; Figure 2 It can be seen that PIM1 expression is elevated in the peripheral blood of mice with ulcerative colitis;

[0021] Figure 3 The figure shows the body weight, disease activity index DAI score and colon pathology score of mice with ulcerative colitis and after treatment with PIM1 inhibitors; Figure 3 Figure a shows the weight statistics of mice, Figure b shows the disease activity index (DAI) score of mice, and Figure c shows the colon pathology score of mice. In addition, the control group in Figures a, b, and c is the control group, the DSS group is the ulcerative colitis group, and the TCS+DSS group is the PIM1 kinase inhibitor treatment group.

[0022] Figure 4 Figure 2 is H&E staining of the colon; the control group is the control group, the DSS group is the ulcerative colitis group, and the TCS+DSS group is the PIM1 kinase inhibitor treatment group;

[0023] Figure 5 The figure shows the results of the open field test OFT; the control group is the control group, the DSS group is the ulcerative colitis group, and the TCS+DSS group is the PIM1 kinase inhibitor treatment group;

[0024] Figure 6 The results of the light-dark box test (LDBT) (assessing anxiety-like behavior) are shown in the figure; the control group is the control group, the DSS group is the ulcerative colitis group, and the TCS+DSS group is the PIM1 kinase inhibitor treatment group;

[0025] Figure 7 Figure 2 is the result of forced swimming FST; the control group is the control group, the DSS group is the ulcerative colitis group, and the TCS+DSS group is the PIM1 kinase inhibitor treatment group;

[0026] Figure 8 The figure shows the results of the tail suspension test (TST) (assessing depressive-like behavior); the control group is the control group, the DSS group is the ulcerative colitis group, and the TCS+DSS group is the PIM1 kinase inhibitor treatment group;

[0027] Figure 9 This is a map of the activity trajectory of mice in a specific area; the control group is the control group, the DSS group is the ulcerative colitis group, and the TCS+DSS group is the PIM1 kinase inhibitor treatment group;

[0028] Figure 10 The figure shows the behavioral patterns of mice under different lighting conditions; among them, the control group is the control group, the DSS group is the ulcerative colitis group, and the TCS+DSS group is the PIM1 kinase inhibitor treatment group. DETAILED DESCRIPTION

[0029] The following examples may help those skilled in the art to more fully understand the present invention, but shall not limit the present invention in any way.

[0030] PIM1 in the present invention is a protein kinase, which is usually involved in various cellular processes in cells.

[0031] The PIM1 kinase inhibitors of the present invention inhibit the activity of PIM1 kinase by competitively binding to the ATP binding site of PIM1 kinase. PIM1 kinase inhibitors can be referred to as PIM1 inhibitors or PIM1 enzyme inhibitors. These terms are essentially the same and refer to compounds that can inhibit the activity of PIM1 kinase. The molecular formula of the PIM1 kinase inhibitor can be C 18 H 11 BrN2O2.

[0032] The application of the PIM1 kinase inhibitor of the present invention involves the regulation of cellular processes by phosphorylating multiple substrates. PIM1 kinase inhibitors not only play a role in autoimmune disease models, but also regulate neural differentiation and regeneration processes, and have the effect of improving intestinal inflammation. Therefore, PIM1 kinase inhibitors can be used to prepare drugs for treating and / or preventing intestinal inflammation, opening up new possibilities for treating and / or preventing intestinal inflammation, and have potential value in the treatment of intestinal inflammation.

[0033] The application of the PIM1 kinase inhibitor of the present invention involves in regulating cellular processes by phosphorylating multiple substrates. PIM1 kinase inhibitors not only play a role in autoimmune disease models, but also regulate neural differentiation and regeneration processes, and have the effect of improving neuropsychiatric comorbidities of intestinal inflammation. Therefore, PIM1 kinase inhibitors can be used to prepare drugs for treating and / or preventing neuropsychiatric comorbidities of intestinal inflammation, opening up new possibilities for treating and / or preventing neuropsychiatric comorbidities of intestinal inflammation, and have potential value in the treatment of neuropsychiatric comorbidities of intestinal inflammation.

[0034] The application of the PIM1 kinase inhibitor of the present invention is that the PIM1 kinase inhibitor participates in the regulation of cellular processes by phosphorylating multiple substrates. The PIM1 kinase inhibitor not only plays a role in autoimmune disease models, but also can regulate neural differentiation and regeneration processes, and has the effect of improving intestinal inflammation and its neuropsychiatric comorbidities. Therefore, the PIM1 kinase inhibitor can be used to prepare drugs for treating and / or preventing intestinal inflammation and its neuropsychiatric comorbidities, opening up new possibilities for treating and / or preventing intestinal inflammation and its neuropsychiatric comorbidities, and has potential value in the treatment of intestinal inflammation and its neuropsychiatric comorbidities.

[0035] The application of the PIM1 kinase inhibitor of the present invention was verified by experiment 1:

[0036] 1) Establishment of an acute colitis model in mice: 3% dextran sulfate sodium (DSS; Catalog No. 160110, MP Biomedicals, USA) dissolved in drinking water was administered orally for 7 consecutive days to establish an acute colitis model in mice. Daily monitoring indicators included weight change, fecal occult blood detection, and stool consistency assessment. The disease activity index (DAI) was calculated based on the following three parameters: weight loss (0: no weight loss; 1: 1-5%; 2: 5-10%; 3: 10-20%; 4: >20%), rectal bleeding (0: normal; 2: positive for occult blood; 4: gross blood in stool), and stool consistency (0: formed stool; 2: loose stool; 4: watery stool).

[0037] 2) Immunofluorescence staining of colon pathological sections confirmed that PIM1 expression is increased in ulcerative colitis; for details, see Figure 1 , Figure 1 PIM1 in this refers to the immunofluorescence staining of PIM1 protein; Figure 1 The DAPI in the text refers to DAPI staining of the cell nucleus; Figure 1 Merge in refers to merging the images stained with PIM1 and DAPI so as to simultaneously observe the positional relationship between PIM1 protein and cell nucleus; Figure 1 It can be seen that PIM1 expression is increased in ulcerative colitis lesions, which suggests that PIM1 is a biomarker of intestinal damage in ulcerative colitis;

[0038] 3) Plasma ELISA assay showed that PIM1 expression in the peripheral blood of mice with ulcerative colitis was elevated; for details, please refer to Figure 2 , Figure 2 The English words represent the following meanings respectively: ELISA: Enzyme-Linked Immunosorbent Assay, which is a commonly used biochemical analysis method used to detect the concentration of specific proteins in samples; Colon: colon, refers to the tissue type tested in the experiment; TNF-α: Tumor Necrosis Factor-alpha, a cytokine involved in regulating immune responses and inflammatory processes; IL-1β: Interleukin-1beta, also a cytokine involved in inflammatory responses and immune regulation; PIM1: Pim-1 protein, a protein kinase involved in processes such as cell proliferation, differentiation and apoptosis; Relative expression: relative expression refers to the change in protein concentration detected in the experiment relative to the control group (usually the Sham group); Sham: sham operation group, refers to the control group that underwent surgical operation but no major experimental treatment; DSS: Dextran Sulfate Sodium, a chemical commonly used to induce experimental colitis; Figure 2 Figure 2 shows the changes in the relative expression levels of TNF-α, IL-1β, and PIM1 in the sham group and the DSS-treated group; asterisks (*) indicate statistical significance, indicating p < 0.05, ** indicating p < 0.01, and *** indicating p < 0.001; Figure 2 It can be seen that PIM1 is a biomarker for ulcerative colitis.

[0039] Example 1

[0040] A use of a PIM1 kinase inhibitor comprises the following steps:

[0041] (1) Establishment of a control group: 8-week-old mice were used and acclimatized to the environment for 7 days as the control group;

[0042] (2) Establishment of ulcerative colitis group (DSS group): 8-week-old mice were gavaged with 3% (w / v) dextran sulfate sodium (DSS; Catalog No. 160110, MP Biomedicals, USA) dissolved in drinking water for 7 consecutive days to establish the ulcerative colitis group; daily monitoring indicators included: body weight change, fecal occult blood test and stool characteristics assessment; disease activity index (DAI) was calculated by the following three parameters: degree of weight loss (0 point: no weight loss; 1 point: 1-5%; 2 points: 5-10%; 3 points: 10-20%; 4 points: >20%), rectal bleeding (0 point: normal; 2 points: positive for occult blood; 4 points: gross blood in stool) and stool characteristics (0 point: formed stool; 2 points: loose stool; 4 points: watery stool);

[0043] (3) Establishment of a PIM1 kinase inhibitor treatment group (TCS+DSS group): 8-week-old mice were acclimated to the environment for 7 days and then pretreated with the PIM1 kinase inhibitor TCS (MCE, Synonyms: SC 204330) (intraperitoneal injection, 5 mg / kg / day, for 5 days). After that, 3% (w / v) dextran sulfate sodium (DSS; Catalog No. 160110, MP Biomedicals, USA) was added to the drinking water to induce colitis.

[0044] (4) Detection:

[0045] 1.1) Body weight was measured in the control group, ulcerative colitis group (DSS group), and PIM1 kinase inhibitor treatment group (TCS+DSS group);

[0046] 1.2) Disease Activity Index (DAI) scores were assessed in the control group, ulcerative colitis group (DSS group), and PIM1 kinase inhibitor treatment group (TCS+DSS group);

[0047] 1.3) Colon pathology scores were performed in the control group, ulcerative colitis group (DSS group), and PIM1 kinase inhibitor treatment group (TCS+DSS group);

[0048] 1.4) Colon H&E staining was performed in the control group, ulcerative colitis group (DSS group), and PIM1 kinase inhibitor treatment group (TCS+DSS group).

[0049] 1.5) Behavioral assessments were performed on mice in the control group, ulcerative colitis group (DSS group), and PIM1 kinase inhibitor-treated group (TCS+DSS group), including the open field test (OFT), the light-dark box test (LDBT) (to assess anxiety-like behaviors), the forced swim test (FST), and the tail suspension test (TST) (to assess depressive-like behaviors).

[0050] The experimental results of the control group, DSS group, and TCS+DSS group are as follows Figure 3-Figure 10 As shown;

[0051] Figure 3 Figure a shows that mice in the DSS group (ulcerative colitis group) showed significant weight loss, while the PIM1 kinase inhibitor treatment group (TCS+DSS group) effectively alleviated the problem of rapid weight loss in mice; Figure 3 Figure b shows that the disease activity index (DAI) of mice in the DSS group (ulcerative colitis group) increased, and the PIM1 kinase inhibitor treatment group (TCS+DSS group) effectively alleviated the problem of rapid increase in the disease activity index (DAI) of mice; Figure 3 Figure c shows that the colon pathology score of mice in the DSS group (ulcerative colitis group) increased, while the colon pathology score of mice in the PIM1 kinase inhibitor treatment group (TCS+DSS group) was effectively reduced. It can be seen that the PIM1 kinase inhibitor treatment group significantly alleviated the symptoms of the DSS group.

[0052] Figure 4 is the H&E staining picture of the colon; the control group is the control group, the DSS group is the ulcerative colitis group, and the TCS+DSS group is the PIM1 kinase inhibitor treatment group; see Figure 4 It can be seen that the DSS group showed severe tissue structural damage, including inflammatory cell infiltration and goblet cell reduction, while the PIM1 kinase inhibitor treatment group (TCS+DSS group) significantly improved these colitis-related injuries; see Figure 3 Test results and Figure 4 The test results show that PIM1 kinase inhibitors can be used to prepare drugs for treating and / or preventing intestinal inflammation, opening up new possibilities for treating and / or preventing intestinal inflammation and having potential value for the treatment of intestinal inflammation.

[0053] Figure 5-10 The experimental results of the open field test OFT / light-dark box test LDBT (assessing anxiety-like behavior) and the forced swim FST / tail suspension test TST (assessing depressive-like behavior) are shown in the figure. Figure 5-10 This suggests that mice with ulcerative colitis in the DSS group exhibited depression- and anxiety-like behaviors; however, the depression and anxiety symptoms in the mice treated with the PIM1 kinase inhibitor were effectively reversed. This suggests that PIM1 kinase inhibitors may be used to prepare drugs for the treatment and / or prevention of neuropsychiatric comorbidities associated with intestinal inflammation.

[0054] In summary, PIM1 kinase inhibitors participate in the regulation of cellular processes by phosphorylating multiple substrates. PIM1 kinase inhibitors not only play a role in autoimmune disease models, but also regulate neural differentiation and regeneration processes, and have the effect of improving intestinal inflammation and its neuropsychiatric comorbidities. Therefore, PIM1 kinase inhibitors can be used to prepare drugs for the treatment and / or prevention of intestinal inflammation and its neuropsychiatric comorbidities, opening up new possibilities for the treatment and / or prevention of intestinal inflammation and its neuropsychiatric comorbidities, and have potential value in the treatment of intestinal inflammation and its neuropsychiatric comorbidities.

[0055] Example 2

[0056] A use of a PIM1 kinase inhibitor comprises the following steps:

[0057] (1) Establishment of a control group: 8-week-old mice were used and acclimatized to the environment for 7 days as the control group;

[0058] (2) Establishment of ulcerative colitis group (DSS group): 8-week-old mice were gavaged with 3% (w / v) dextran sulfate sodium (another brand) dissolved in drinking water for 7 consecutive days to establish the ulcerative colitis group; daily monitoring indicators included: body weight change, fecal occult blood test and stool characteristics assessment; disease activity index (DAI) was calculated by the following three parameters: degree of weight loss (0 point: no weight loss; 1 point: 1-5%; 2 points: 5-10%; 3 points: 10-20%; 4 points: >20%), rectal bleeding (0 point: normal; 2 points: positive for occult blood; 4 points: gross blood in stool) and stool characteristics (0 point: formed stool; 2 points: loose stool; 4 points: watery stool);

[0059] (3) Establishment of a PIM1 kinase inhibitor treatment group (TCS+DSS group): 8-week-old mice were first acclimated to the environment for 7 days, and then pretreated with the PIM1 kinase inhibitor TCS (another brand) (intraperitoneal injection, 5 mg / kg / day, for 5 days). After that, 3% (w / v) dextran sulfate sodium (another brand) was added to the drinking water to induce colitis.

[0060] (4) Detection:

[0061] 1.1) Body weight was measured in the control group, ulcerative colitis group (DSS group), and PIM1 kinase inhibitor treatment group (TCS+DSS group);

[0062] 1.2) Disease Activity Index (DAI) scores were assessed in the control group, ulcerative colitis group (DSS group), and PIM1 kinase inhibitor treatment group (TCS+DSS group);

[0063] 1.3) Colon pathology scores were performed in the control group, ulcerative colitis group (DSS group), and PIM1 kinase inhibitor treatment group (TCS+DSS group);

[0064] 1.4) Colon H&E staining was performed in the control group, ulcerative colitis group (DSS group), and PIM1 kinase inhibitor treatment group (TCS+DSS group).

[0065] 1.5) Behavioral assessments were performed on mice in the control group, ulcerative colitis group (DSS group), and PIM1 kinase inhibitor-treated group (TCS+DSS group), including the open field test (OFT), the light-dark box test (LDBT) (to assess anxiety-like behaviors), the forced swim test (FST), and the tail suspension test (TST) (to assess depressive-like behaviors).

[0066] The experimental results of the control group, DSS group, and TCS+DSS group were consistent with those in Example 1;

[0067] Mice in the DSS group (ulcerative colitis group) showed significant weight loss, while the PIM1 kinase inhibitor treatment group (TCS+DSS group) effectively alleviated the rapid weight loss of mice. The disease activity index (DAI) of mice in the DSS group (ulcerative colitis group) increased, while the PIM1 kinase inhibitor treatment group (TCS+DSS group) effectively alleviated the rapid increase in the disease activity index (DAI) of mice. The colon pathology score of mice in the DSS group (ulcerative colitis group) increased, while the PIM1 kinase inhibitor treatment group (TCS+DSS group) effectively reduced the colon pathology score of mice. It can be seen that the PIM1 kinase inhibitor treatment group significantly alleviated the symptoms of the DSS group.

[0068] The DSS group showed severe tissue structural damage, including inflammatory cell infiltration and goblet cell reduction, while the PIM1 kinase inhibitor treatment group (TCS+DSS group) significantly improved these colitis-related injuries. This shows that PIM1 kinase inhibitors can be used to prepare drugs for the treatment and / or prevention of intestinal inflammation, opening up new possibilities for the treatment and / or prevention of intestinal inflammation and having potential value in the treatment of intestinal inflammation.

[0069] Results from the open field test (OFT) / light-dark box test (LDBT) (assessing anxiety-like behaviors) and the forced swim test (FST) / tail suspension test (TST) (assessing depressive-like behaviors) suggested that mice with ulcerative colitis in the DSS group exhibited depression- and anxiety-like behaviors. Treatment with a PIM1 kinase inhibitor effectively reversed these depression and anxiety symptoms in mice. This suggests that PIM1 kinase inhibitors could be used to develop drugs for the treatment and / or prevention of neuropsychiatric comorbidities associated with intestinal inflammation.

[0070] In summary, PIM1 kinase inhibitors participate in the regulation of cellular processes by phosphorylating multiple substrates. PIM1 kinase inhibitors not only play a role in autoimmune disease models, but also regulate neural differentiation and regeneration processes, and have the effect of improving intestinal inflammation and its neuropsychiatric comorbidities. Therefore, PIM1 kinase inhibitors can be used to prepare drugs for the treatment and / or prevention of intestinal inflammation and its neuropsychiatric comorbidities, opening up new possibilities for the treatment and / or prevention of intestinal inflammation and its neuropsychiatric comorbidities, and have potential value in the treatment of intestinal inflammation and its neuropsychiatric comorbidities.

[0071] Example 3

[0072] A use of a PIM1 kinase inhibitor comprises the following steps:

[0073] (1) Establishment of a control group: 8-week-old mice were used and acclimatized to the environment for 7 days as the control group;

[0074] (2) Establishment of infectious colitis group (DSS group): 8-week-old mice were used to establish the infectious colitis group by administering C. difficile bacterial solution through the digestive tract; daily monitoring indicators included: weight change, fecal occult blood test, and stool characteristics assessment; the disease activity index (DAI) was calculated based on the following three parameters: weight loss (0 point: no weight loss; 1 point: 1-5%; 2 points: 5-10%; 3 points: 10-20%; 4 points: >20%), rectal bleeding (0 point: normal; 2 points: positive for occult blood; 4 points: gross blood in stool), and stool characteristics (0 point: formed stool; 2 points: loose stool; 4 points: watery stool);

[0075] (3) Establish a PIM1 kinase inhibitor treatment group (TCS+DSS group): 8-week-old mice with infectious colitis were injected with the PIM1 kinase inhibitor TCS (another brand) (intraperitoneal injection, 5 mg / kg / day, for 5 days);

[0076] (4) Detection:

[0077] 1.1) Body weight was measured in the control group, ulcerative colitis group (DSS group), and PIM1 kinase inhibitor treatment group (TCS+DSS group);

[0078] 1.2) Disease Activity Index (DAI) scores were assessed in the control group, ulcerative colitis group (DSS group), and PIM1 kinase inhibitor treatment group (TCS+DSS group);

[0079] 1.3) Colon pathology scores were performed in the control group, ulcerative colitis group (DSS group), and PIM1 kinase inhibitor treatment group (TCS+DSS group);

[0080] 1.4) Colon H&E staining was performed in the control group, ulcerative colitis group (DSS group), and PIM1 kinase inhibitor treatment group (TCS+DSS group).

[0081] 1.5) Behavioral assessments were performed on mice in the control group, ulcerative colitis group (DSS group), and PIM1 kinase inhibitor-treated group (TCS+DSS group), including the open field test (OFT), the light-dark box test (LDBT) (to assess anxiety-like behaviors), the forced swim test (FST), and the tail suspension test (TST) (to assess depressive-like behaviors).

[0082] The experimental results of the control group, DSS group, and TCS+DSS group were consistent with those in Example 1;

[0083] Mice in the DSS group (ulcerative colitis group) showed significant weight loss, while the PIM1 kinase inhibitor treatment group (TCS+DSS group) effectively alleviated the rapid weight loss of mice. The disease activity index (DAI) of mice in the DSS group (ulcerative colitis group) increased, while the PIM1 kinase inhibitor treatment group (TCS+DSS group) effectively alleviated the rapid increase in the disease activity index (DAI) of mice. The colon pathology score of mice in the DSS group (ulcerative colitis group) increased, while the PIM1 kinase inhibitor treatment group (TCS+DSS group) effectively reduced the colon pathology score of mice. It can be seen that the PIM1 kinase inhibitor treatment group significantly alleviated the symptoms of the DSS group.

[0084] The DSS group showed severe tissue structural damage, including inflammatory cell infiltration and goblet cell reduction, while the PIM1 kinase inhibitor treatment group (TCS+DSS group) significantly improved these colitis-related injuries. This shows that PIM1 kinase inhibitors can be used to prepare drugs for the treatment and / or prevention of intestinal inflammation, opening up new possibilities for the treatment and / or prevention of intestinal inflammation and having potential value in the treatment of intestinal inflammation.

[0085] Results from the open field test (OFT) / light-dark box test (LDBT) (assessing anxiety-like behaviors) and the forced swim test (FST) / tail suspension test (TST) (assessing depressive-like behaviors) suggested that mice with ulcerative colitis in the DSS group exhibited depression- and anxiety-like behaviors. Treatment with a PIM1 kinase inhibitor effectively reversed these depression and anxiety symptoms in mice. This suggests that PIM1 kinase inhibitors could be used to develop drugs for the treatment and / or prevention of neuropsychiatric comorbidities associated with intestinal inflammation.

[0086] In summary, PIM1 kinase inhibitors participate in the regulation of cellular processes by phosphorylating multiple substrates. PIM1 kinase inhibitors not only play a role in autoimmune disease models, but also regulate neural differentiation and regeneration processes, and have the effect of improving intestinal inflammation and its neuropsychiatric comorbidities. Therefore, PIM1 kinase inhibitors can be used to prepare drugs for the treatment and / or prevention of intestinal inflammation and its neuropsychiatric comorbidities, opening up new possibilities for the treatment and / or prevention of intestinal inflammation and its neuropsychiatric comorbidities, and have potential value in the treatment of intestinal inflammation and its neuropsychiatric comorbidities.

[0087] It can be seen that the application of the PIM1 kinase inhibitor of the present invention, PIM1 kinase inhibitors participate in the regulation of cellular processes by phosphorylating multiple substrates. PIM1 kinase inhibitors not only play a role in autoimmune disease models, but also can regulate neural differentiation and regeneration processes, and have the effect of improving intestinal inflammation. Therefore, PIM1 kinase inhibitors can be used to prepare drugs for treating and / or preventing intestinal inflammation, opening up new possibilities for treating and / or preventing intestinal inflammation, and have potential value in the treatment of intestinal inflammation.

[0088] The application of the PIM1 kinase inhibitor of the present invention involves in regulating cellular processes by phosphorylating multiple substrates. PIM1 kinase inhibitors not only play a role in autoimmune disease models, but also regulate neural differentiation and regeneration processes, and have the effect of improving neuropsychiatric comorbidities of intestinal inflammation. Therefore, PIM1 kinase inhibitors can be used to prepare drugs for treating and / or preventing neuropsychiatric comorbidities of intestinal inflammation, opening up new possibilities for treating and / or preventing neuropsychiatric comorbidities of intestinal inflammation, and have potential value in the treatment of neuropsychiatric comorbidities of intestinal inflammation.

[0089] The application of the PIM1 kinase inhibitor of the present invention is that the PIM1 kinase inhibitor participates in the regulation of cellular processes by phosphorylating multiple substrates. The PIM1 kinase inhibitor not only plays a role in autoimmune disease models, but also can regulate neural differentiation and regeneration processes, and has the effect of improving intestinal inflammation and its neuropsychiatric comorbidities. Therefore, the PIM1 kinase inhibitor can be used to prepare drugs for treating and / or preventing intestinal inflammation and its neuropsychiatric comorbidities, opening up new possibilities for treating and / or preventing intestinal inflammation and its neuropsychiatric comorbidities, and has potential value in the treatment of intestinal inflammation and its neuropsychiatric comorbidities.

[0090] Although the present invention has been described in detail above using general descriptions and specific embodiments, it will be apparent to those skilled in the art that modifications and improvements may be made based on the present invention. Therefore, such modifications and improvements, which do not depart from the spirit of the present invention, are intended to be within the scope of protection claimed herein.

Claims

1. A use of a PIM1 kinase inhibitor, characterized in that: Use of the PIM1 kinase inhibitor in preparing a drug for treating and / or preventing intestinal inflammation.

2. The use of the PIM1 kinase inhibitor according to claim 1, characterized in that: The intestinal inflammation includes: one or more of ulcerative colitis, Crohn's disease, infectious enteritis, ischemic enteritis, drug-induced enteritis, radiation enteritis, autoimmune enteritis, and other types of intestinal inflammation.

3. The use of the PIM1 kinase inhibitor according to claim 1 or 2, characterized in that: The administration method of the drug for treating and / or preventing intestinal inflammation includes one or more of injection administration and rectal administration.

4. A use of a PIM1 kinase inhibitor, characterized in that: Use of the PIM1 kinase inhibitor in the preparation of drugs for treating and / or preventing neuropsychiatric comorbidities of intestinal inflammation.

5. The use of the PIM1 kinase inhibitor according to claim 4, characterized in that: The neuropsychiatric comorbidities of intestinal inflammation include: one or more of depression and anxiety.

6. The use of the PIM1 kinase inhibitor according to claim 4 or 5, characterized in that: The administration method of the drug for treating and / or preventing neuropsychiatric comorbidities of intestinal inflammation includes one or more of injection administration and rectal administration.

7. A use of a PIM1 kinase inhibitor, characterized in that: Use of the PIM1 kinase inhibitor in the preparation of drugs for treating and / or preventing intestinal inflammation and its neuropsychiatric comorbidities.

8. The use of the PIM1 kinase inhibitor according to claim 7, characterized in that: The intestinal inflammation includes: one or more of ulcerative colitis, Crohn's disease, infectious enteritis, ischemic enteritis, drug-induced enteritis, radiation enteritis, autoimmune enteritis, and other types of intestinal inflammation.

9. The use of the PIM1 kinase inhibitor according to claim 7, characterized in that: The neuropsychiatric comorbidities of intestinal inflammation include: one or more of depression and anxiety.

10. The use of the PIM1 kinase inhibitor according to any one of claims 7 to 9, characterized in that: The administration method of the drug for preparing the treatment and / or prevention of intestinal inflammation and its neuropsychiatric comorbidities includes: one or more of injection administration and rectal administration.

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