Use of a compound targeting snd1

Abstract

The application discloses application of a compound targeting SND1, and is characterized by application of the compound targeting SND1 in preparation of an SND1 inhibitor, and a structural formula of the compound targeting SND1 is as follows: The application carries out inhibitor screening on Staphylococcal Nuclease and Tudor Domain Containing 1 (SND1) protein mediating tumorigenesis and development, and it is found for the first time that the compound as shown in the structural formula I can target SND1, has good inhibitory activity on various types of human cancer cells, and provides an optional scheme for broad-spectrum anticancer drugs. The compound applied in the application can be artificially synthesized, and production cost is low.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to the application of a compound that targets SND1. Background Technology

[0002] Cancer, as one of the major diseases seriously threatening human health, still faces many challenges in its treatment. Chemotherapy is one of the commonly used cancer treatments, but it suffers from low selectivity, often damaging not only tumor cells but also normal cells, leading to significant toxic side effects. Furthermore, long-term use of chemotherapy drugs can easily induce multidrug resistance, thereby reducing treatment effectiveness.

[0003] Staphylococcal nuclease-containing domain 1 (SND1) is a multifunctional transcriptional coactivator highly expressed in various tumors. SND1 participates in tumorigenesis and progression by regulating the cell cycle, influencing transcription and post-transcriptional processes, and promoting tumor cell proliferation, migration, invasion, and DNA damage repair. Therefore, SND1 is considered an important potential target for tumor diagnosis and treatment. However, currently, there are no clinical drugs that specifically target SND1. Summary of the Invention

[0004] The purpose of this invention is to provide an application of a compound that targets SND1.

[0005] The objective of this invention is achieved through the application of the SND1-targeting compound in the preparation of SND1 inhibitors. The structural formula of the SND1-targeting compound is as follows, namely, Formula I:

[0006]

[0007] Formula I.

[0008] The use of the SND1-targeting compound in the preparation of drugs for the prevention and / or treatment of SND1-mediated diseases.

[0009] The disease mediated by SND1 is cancer.

[0010] The cancers mentioned are SND1-mediated breast cancer, colorectal cancer, leukemia, esophageal cancer, pancreatic cancer, glioma, kidney cancer, skin cancer, osteosarcoma, ovarian cancer, or prostate cancer.

[0011] The compound targeting SND1 can inhibit the proliferation of various cancer cells; the cancer cells are at least one of breast cancer, colorectal cancer, leukemia, esophageal cancer, pancreatic cancer, glioma, kidney cancer, skin cancer, osteosarcoma, ovarian cancer, and prostate cancer cells.

[0012] Preferably, the compound is used in combination with a pharmaceutically acceptable carrier. When used as a drug, the compound can be used directly or in the form of a pharmaceutical composition. When used, the compound is generally administered by injection to patients requiring treatment.

[0013] Preferably, the compound or a pharmaceutically acceptable salt thereof is used as the active pharmaceutical ingredient.

[0014] Preferably, the mass fraction of the active pharmaceutical ingredient is 0.1% to 99%; more preferably, the mass fraction of the active pharmaceutical ingredient is 0.1% to 20%.

[0015] This invention offers the following advantages: It screens for inhibitors of the tumor protein Staphylococcus aureus containing nuclease domain 1 (SND1), and for the first time discovers that compounds of structural formula I exhibit good inhibitory activity against various types of human cancer cells. Furthermore, these compounds can effectively inhibit tumor growth in vivo at effective doses without exhibiting hepatotoxicity or nephrotoxicity, providing a potential option for broad-spectrum anticancer drugs. The compounds involved in this invention can be obtained through chemical synthesis, which is simple, low-cost, and has the potential for large-scale production. Attached Figure Description

[0016] Figure 1 The structural formulas of two compounds obtained based on the SND1 protein structure screening are shown below. I represents the structural formula of compound I, and II represents the structural formula of compound II.

[0017] Figure 2 The results show the inhibitory activity test results for the two compounds;

[0018] In the figure, A represents the results of the inhibitory activity test of the two compounds on human breast cancer cells MDA-MB-231; B represents the results of the inhibitory activity test of the two compounds on human breast cancer cells MCF7; ns in the figure indicates that there is no statistically significant difference between the two groups of data, * indicates that the statistical difference between the two groups of data is P<0.05, and ** indicates that the statistical difference between the two groups of data is P<0.01.

[0019] Figure 3 To detect the binding affinity of compound I to SND1 using surface plasmon resonance (SPR) technology;

[0020] Where A represents the reaction curves of the binding and dissociation process of compound I with chip-fixed receptor SND1 at different concentrations;

[0021] B represents the fitted curve of the binding response value of compound I with SND1 at different concentrations. The fitted curve shows that the binding constant KD of compound I with SND1 is 4.195 μM.

[0022] Figure 4To evaluate the effect of compound I on the structural stability of the SND1 protein using thermal migration experiments;

[0023] Where A represents the content of SND1 protein in MDA-MB-231 cells after treatment with 10 μM compound I at different temperatures for 3 min, and detection by Western blotting.

[0024] B represents the relative content of SND1 after heat treatment at different temperatures, relative to the internal reference gene β-actin protein.

[0025] Figure 5 The results show the in vivo inhibition of compound I on human breast cancer xenografts in nude mice;

[0026] In this case, A involved euthanasia of nude mice 14 days after drug administration, followed by removal of tumor tissue and photographic observation.

[0027] B represents the tumor volume measured every 3 days after drug administration, as shown in a line graph;

[0028] C represents the tumor weight after treatment with dimethyl sulfoxide (DMSO) as a control group and after administration of compound I at a dose of 40 mg / kg.

[0029] D represents the weight of nude mice measured every 3 days after drug administration, as shown in a line graph;

[0030] After administration, nude mice were anesthetized, orbital blood was collected, and serum alanine aminotransferase and aspartate aminotransferase activities were measured to evaluate the hepatotoxicity of compound I.

[0031] G represents the detection of serum creatinine levels to evaluate the nephrotoxicity of compound I; in the figure, ns indicates that there is no statistically significant difference between the two groups, and * indicates that the statistical difference between the two groups is P<0.05. Detailed Implementation

[0032] The present invention will be further described below with reference to embodiments and accompanying drawings, but this does not limit the present invention in any way. Any modifications or substitutions made based on the teachings of the present invention shall fall within the protection scope of the present invention.

[0033] The application of the SND1-targeting compound described in this invention in the preparation of SND1 inhibitors, wherein the structural formula of the SND1-targeting compound is as follows:

[0034]

[0035] Formula I.

[0036] The use of the SND1-targeting compound in the preparation of drugs for the prevention and / or treatment of SND1-mediated diseases.

[0037] The disease mediated by SND1 is cancer.

[0038] The cancers mentioned are SND1-mediated breast cancer, colorectal cancer, leukemia, esophageal cancer, pancreatic cancer, glioma, kidney cancer, skin cancer, osteosarcoma, ovarian cancer, or prostate cancer.

[0039] The invention will be further illustrated below with specific implementation examples:

[0040] The human breast cancer cells described in the following examples are human breast cancer cells MDA-MB-231, HCC1937, MCF7, HCC1806, BT549, SUM149PT, BT474, MDA-MB-453, MDA-MB-468, SKBR3, and HCC1500; the human colorectal cancer cells are human colorectal cancer cells HCT-8 and RKO; the human leukemia cells are human acute T-lymphoblastic leukemia cells JurKat; the human esophageal cancer cells are human esophageal squamous cell carcinoma cells KYSE-180; the human pancreatic cancer cells are human pancreatic cancer cells SW1990; the human glioma cells are human glioblastoma cells U87; the human renal cancer cells are human clear cell renal cancer cells 786-O; the human skin cancer cells are human malignant melanoma cells A-375; the human osteosarcoma cells are human osteosarcoma cells MG63; the human ovarian cancer cells are human ovarian cancer cells Hey; and the human prostate cancer cells are human prostate cancer cells PC3. The conventional cancer cells used above were all obtained from Kunming Medical University.

[0041] Unless otherwise specified, all reagents used in the embodiments of this invention are commercially available. RPMI 1640 medium, DMEM medium, and fetal bovine serum were purchased from Biological Industries; phosphate-buffered saline (PBS), 0.25% trypsin, and CCK8 reagent were purchased from Beyotime Biotechnology Co., Ltd.

[0042] Cell lines were cultured in DMEM or RPMI 1640 medium containing 10% fetal bovine serum at 37°C, 5% CO2 and saturated humidity.

[0043] The structural formulas of the compounds used in the following examples are as follows: Figure 1As shown, compound I is named 4-[(5-bromo-2-hydroxy-3-methoxyphenyl)methylene]-1-(3-bromophenyl)-3,5-pyrazolidinedione, with SMILES number C1(=CC2=CC(Br)=CC(OC)=C2O)C(=O)NN(C2=CC=CC(Br)=C2)C1=O; compound II is named 5-(2-ethoxyphenyl)-3-(4-methylphenyl) The following compounds were synthesized by Chengdu Ruizhi Chemical Research Co., Ltd.: 3a,6a-dihydrospiro[furano[3,4-c]pyrrole-1,2'-indene]-1',3',4,6(3H,5H)-tetraone, SMILES number CCOc1ccccc1N1C(C2C(C1=O)C1(C(c3ccccc3C1=O)=O)OC2c1ccc(C)cc1)=O. All were synthesized with a purity >95%.

[0044] Example 1

[0045] Synthesis of Compound I

[0046] Compound I was synthesized as follows: The starting material was 2,4-dihydroxy-5-bromoaniline (300 mg, 1.6 mmol), dissolved in tetrahydrofuran (THF, 10 mL), and phosphorus trichloride (PCl3, 1 mL) was added. The mixture was stirred at 65 °C for 1 hour. After the reaction was complete, the solvent was removed by vacuum evaporation, and the crude product was purified by silica gel column chromatography (eluent: THF:hexane = 3:2) to give intermediate 2 (150 mg, yield 35.1%), a yellow solid. The molecular weight of this intermediate was confirmed by LC-MS to be 254.9, and the purity was 68.82% (detection wavelength 214 nm). Intermediate 2 (150 mg, 0.59 mmol) was mixed with pyridine (1 mL) in ethanol (20 mL) and stirred overnight at 85 °C. After the reaction was complete, the mixture was filtered, and the filtrate was washed with ethanol to give the target compound I, a yellow solid, whose structure was confirmed by NMR.

[0047] Example 2

[0048] Antitumor activity test

[0049] To evaluate the differences in the inhibitory activity of the compounds provided in this invention against breast cancer cell proliferation, the Cell Counting Kit-8 (CCK-8) method was used to detect the inhibitory effect of the compounds on cancer cell growth. The CCK-8 reagent contains WST-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfonic acid benzene)-2H-tetrazole monosodium salt), which can be catalyzed and reduced by dehydrogenases in living cells to generate a highly water-soluble orange-yellow formazan product. This product has a specific absorption peak at 450 nm, and its absorbance is linearly positively correlated with the number of living cells, which can be used to assess cell proliferation activity.

[0050] Compounds I and II were dissolved in DMSO (dimethyl sulfoxide) solution to prepare concentrated solutions with concentrations of 2500, 1500, 800, 400, 200, and 100 μM, respectively. Breast cancer cells MDA-MB-231 and MCF7 were cultured at 1 × 10⁻⁶ cells per well. 4 Cells were seeded at a density of 1000 μL in 96-well plates and cultured for 24 h in a constant temperature incubator at 37°C, 5% CO2, and saturated humidity. Then, different concentrations of compounds were added to each well: 25 μM, 15 μM, 8 μM, 4 μM, 2 μM, and 1 μM. The final concentration of DMSO was 1%. The control group received only an equal volume of DMSO in the cell culture. After 72 h of further culture, 10 μL of CCK8 solution was added to each well, and the cells were incubated in the dark for 1 h. The absorbance at 450 nm was measured using a microplate reader. The percentage of absorbance in the experimental group relative to the absorbance in the control group represents the cell viability. Figure 2 ).

[0051] The results are as follows Figure 2 As shown, compound I exhibited a dose-dependent effect in inhibiting the proliferation of breast cancer cells MDA-MB-231 and MCF7. With increasing concentration, the inhibitory effect of compound I on cell viability significantly increased, especially at concentrations of 15 μM and above, where cell viability decreased to below 50%. Compound II showed a weaker inhibitory effect; cell viability remained above 50% at 50 μM. Comparative analysis showed that at concentrations of 25 μM, 15 μM, 8 μM, and 4 μM, the inhibitory activity of compound I against both MDA-MB-231 and MCF7 was significantly higher than that of compound II. P <0.05, P <0.01).

[0052] Example 3

[0053] Binding affinity of compound I to SND1

[0054] To assess the binding affinity of compound I to SND1, surface plasmon resonance (SPR) technology was used to detect the binding affinity between compound I and SND1. The SND1 protein was coupled to an SPR sensor chip, and different concentrations of compound I were passed through the chip. By detecting changes in the response value during the binding and dissociation of compound I with SND1 protein, the equilibrium dissociation constant (KD) between compound I and SND1 was calculated.

[0055] The results are as follows Figure 3 As shown, after different concentrations of compound I flow through the chip, the response value gradually increases with increasing concentration. The dissociation constant (KD) calculated from the fitted curve is 4.195 μM, indicating that there is a high binding affinity between compound I and SND1 protein.

[0056] Example 4

[0057] Compound I promotes the structural stability of SND1.

[0058] The effect of compound I on the structural stability of the SND1 protein was evaluated using a cellular thermal shift assay (CETSA). The principle of the CETSA is to use the changes in the thermal stability of proteins at different temperatures to detect the binding of small molecule compounds to target proteins. When a protein binds to a small molecule ligand, its structure usually becomes more stable, and its thermal stability is enhanced.

[0059] MDA-MB-231 cells were cultured, and when the cells reached approximately 80% confluence, they were treated with 10 μM compound I for 4 h. The cells were then collected and divided into 8 aliquots, which were heat-treated at 40.3, 42.6, 44.3, 46.3, 48.3, 50.3, 52.1, and 54.6 °C for 3 min each. Total cellular protein was extracted from each aliquot, and the SND1 protein content was detected by Western blotting.

[0060] like Figure 4 As shown, the stability of SND1 protein gradually decreases with increasing temperature. In the DMSO control group, SND1 protein rapidly degraded above 46.3℃, becoming virtually undetectable at 54.6℃. However, in the compound I treatment group, the degradation rate of SND1 protein at the same temperature was significantly slowed, indicating that compound I can significantly improve the thermal stability of SND1 protein. Quantitative analysis results showed that the relative content of SND1 protein in the compound I group was higher than that in the control group at temperatures of 48.3℃ and above, indicating that the binding of compound I significantly enhanced the stability of SND1 protein.

[0061] Example 5

[0062] Inhibition of breast cancer cells by compound I

[0063] The inhibitory effect of compound I on breast cancer cells was detected using the CCK-8 (Cell Counting Kit-8) method. Breast cancer cells MDA-MB-231, HCC1937, MCF7, HCC1806, BT549, SUM149PT, BT474, MDA-MB-453, MDA-MB-468, SKBR3, and HCC1500 were cultured and seeded in 96-well plates, with 1 × 10⁶ cells per well. 4 Cells were cultured at 37°C, 5% CO2, and saturated humidity for 24 h. Compound I was dissolved in DMSO solution, and then concentrated to 5000, 2500, 1500, 1000, 800, 400, 200, and 100 μM. Different concentrations of the compound were added to each well of cell culture, with final concentrations of 50 μM, 25 μM, 15 μM, 10 μM, 8 μM, 4 μM, 2 μM, and 1 μM, respectively. The final concentration of DMSO was 1%. The control group cell culture was treated with the same volume of DMSO. After 72 h of incubation, 10 μL of CCK8 was added to each well, and after another 1 h of incubation, the absorbance at 450 nm was measured using a microplate reader. The half-maximal inhibitory concentration (IC50) of compound I on cell proliferation was calculated. 50 The results are shown in Table 1.

[0064] Table 1. Half-maximal inhibitory concentration (IC50) of compound I on human breast cancer cell lines. 50 (μM)

[0065]

[0066] As shown in Table 1, compound I exhibited strong cytotoxic activity against human breast cancer cell lines MDA-MB-231, HCC1937, MCF7, HCC1806, BT549, SUM149PT, BT474, MDA-MB-468, SKBR3, and HCC1500. (IC500) 50 The corresponding values ​​were 5.789 μM, 3.412 μM, 8.529 μM, 7.392 μM, 8.413 μM, 12.81 μM, 18.82 μM, 9.798 μM, 20.92 μM, 10.42 μM, and 5.941 μM, respectively.

[0067] Example 6

[0068] Inhibition of colorectal cancer cells by compound I

[0069] In Example 5, the human breast cancer cells were replaced with human colorectal cancer cells HCT-8 and RKO, and all other procedures were the same as in Example 5. 50The results are shown in Table 2.

[0070] Table 2. Half-maximal inhibitory concentration (IC50) of compound I on human colorectal cancer cell lines. 50 (μM)

[0071]

[0072] As shown in Table 2, compound I exhibits strong cytotoxic activity against human colorectal cancer cells HCT-8 and RKO cell lines, with an IC50 concentration of [missing information]. 50 The values ​​were 3.393 μM and 12.17 μM, respectively.

[0073] Example 7

[0074] Inhibition of leukemia cells by compounds

[0075] The human breast cancer cells from Example 5 were replaced with human leukemia cells (Jurkat). Other procedures were the same as in Example 5. 50 The results are shown in Table 3.

[0076] Table 3. Half-maximal inhibitory concentration (IC50) of compound I on the human leukemia cell line Jurkat. 50 (μM)

[0077]

[0078] As shown in Table 3, compound I exhibits strong cytotoxic activity against the human leukemia cell line Jurkat, with an IC50 value of [missing information]. 50 It is 3.365 μM.

[0079] Example 8

[0080] Inhibition of esophageal cancer cells by compounds

[0081] In Example 5, the human breast cancer cells were replaced with human esophageal cancer cells KYSE-180, and all other procedures were the same as in Example 5. 50 The results are shown in Table 4.

[0082] Table 4. Half-maximal inhibitory concentration (IC50) of compound I on the human esophageal cancer cell line KYSE-180. 50 (μM)

[0083]

[0084] As shown in Table 4, compound I exhibits strong cytotoxic activity against the human esophageal cancer cell line KYSE-180, with an IC50 value of [missing value]. 50 It is 9.86 μM.

[0085] Example 9

[0086] Inhibition of pancreatic cancer cells by compounds

[0087] The human breast cancer cells from Example 5 were replaced with human pancreatic cancer cells SW1990, and all other procedures were the same as in Example 5. 50 The results are shown in Table 5.

[0088] Table 5. Half-maximal inhibitory concentration (IC50) of compound I on human pancreatic cancer cell line SW1990. 50 (μM)

[0089]

[0090] As shown in Table 5, compound I exhibits strong cytotoxic activity against the human pancreatic cancer cell line SW1990, with an IC50 value of [missing value]. 50 The value is 28.10 μM.

[0091] Example 10

[0092] Inhibition of glioma by compounds

[0093] Replace the human breast cancer cells from Example 5 with human glioma cells U87, and perform the same procedures as in Example 5. 50 The results are shown in Table 6.

[0094] Table 6. Half-maximal inhibitory concentration (IC50) of compound I on human glioma cell line U87. 50 (μM)

[0095]

[0096] As shown in Table 6, compound I exhibits strong cytotoxic activity against the human glioblastoma U87 cell line, with an IC50 value of [missing value]. 50 It is 16.47 μM.

[0097] Example 11

[0098] Inhibition of renal cell carcinoma cells by compounds

[0099] The human breast cancer cells from Example 5 were replaced with human renal cell carcinoma cells 786-O, and all other operations were the same as in Example 5. 50 The results are shown in Table 7.

[0100] Table 7. Half-maximal inhibitory concentration (IC50) of compound I on human renal cell carcinoma 786-O cell line. 50 (μM)

[0101]

[0102] As shown in Table 7, compound I exhibits strong cytotoxic activity against the human renal cell carcinoma 786-O cell line, with an IC50 value of [missing value]. 50 It is 18.06 μM.

[0103] Example 12

[0104] The compound's inhibitory effect on skin cancer cells

[0105] In Example 5, the human breast cancer cells were replaced with human skin cancer cells A-375, and all other procedures were the same as in Example 5. 50 The results are shown in Table 8.

[0106] Table 8. Half-maximal inhibitory concentration (IC50) of compound I on human skin cancer cell line A-375. 50 (μM)

[0107]

[0108] As shown in Table 8, compound I exhibits strong cytotoxic activity against the human skin cancer cell line A-375, with an IC50 value of [missing value]. 50 It is 10.25 μM.

[0109] Example 13

[0110] Inhibition of osteosarcoma cells by compounds

[0111] In Example 5, the human breast cancer cells were replaced with human osteosarcoma cells MG63, and all other procedures were the same as in Example 5. 50 The results are shown in Table 9.

[0112] Table 9. Half-maximal inhibitory concentration (IC50) of compound I on human osteosarcoma cell line MG63 50 (μM)

[0113]

[0114] As shown in Table 9, compound I exhibits strong cytotoxic activity against the human osteosarcoma MG63 cell line, with an IC50 value of [missing value]. 50 The value is 21.21 μM.

[0115] Example 14

[0116] The inhibitory effect of the compound on ovarian cancer cells

[0117] In Example 5, the human breast cancer cells were replaced with human ovarian cancer cells (Hey), and all other procedures were the same as in Example 5. 50 The results are shown in Table 10.

[0118] Table 10. Half-maximal inhibitory concentration (IC50) of compound I on human ovarian cancer cell line Hey.50 (μM)

[0119]

[0120] As shown in Table 10, compound I exhibits strong cytotoxic activity against the Hey human ovarian cancer cell line, with an IC50 concentration of [missing value]. 50 It is 9.891 μM.

[0121] Example 15

[0122] The inhibitory effect of the compound on prostate cancer cells

[0123] In Example 5, the human breast cancer cells were replaced with human prostate cancer cells PC3, and all other procedures were the same as in Example 5. 50 The results are shown in Table 11.

[0124] Table 11. Half-maximal inhibitory concentration (IC50) of compound I on human prostate cancer cell line PC3. 50 (μM)

[0125]

[0126] As shown in Table 11, compound I exhibits strong cytotoxic activity against the human prostate cancer cell line PC3, with an IC50 concentration of 100 mg / kg. 50 The value is 38.42 μM.

[0127] Example 16

[0128] In vivo antitumor activity assay of compound I

[0129] HCC1806 cells in logarithmic growth phase were digested with trypsin, centrifuged to remove supernatant, resuspended in pre-cooled 1×PBS, counted, and the concentration was adjusted to 2x10⁻¹. 7 Cells / ml, 50μL of cell suspension was taken from each spot (i.e., 10 cells / ml). 6 Add 25 μL of matrix gel to each cell and mix well. Inject the mixture into the axilla of nude mice using a syringe. Measure the tumor volume one week after inoculation, when the subcutaneous tumor volume reaches 50–70 mm. 3 Nude mice were randomly divided into a DMSO control group and a compound I (40 mg / kg) group, with four mice in each group. Compound I was prepared using 10% DMSO, 5% Tween 80, 40% PEG 400, and 45% phosphate buffer, and 100 μL was administered intraperitoneally to each mouse. The DMSO control group was injected with the solution without compound I. Administration was repeated every two days for 14 consecutive days. During this period, mouse body weight and tumor volume were measured regularly (tumor volume = 0.5 x long axis x wide axis). 2 After drug administration, the nude mice were euthanized, the tumor tissue was separated, weighed, photographed, and serum was collected for liver and kidney function testing. The drug used in this example was compound I.

[0130] Figure 5 The results show the inhibitory effect of compound I on human breast cancer in vivo. Figure 5 Image A is a picture of the tumor after the drug administration was completed. Figure 5 B represents the tumor volume measured every 3 days after drug treatment, and is represented by a line graph. Figure 5 C represents the tumor weight after the medication was completed, as shown in a bar chart. Figure 5 According to AC, compared with the DMSO control group, the volume and weight of breast cancer tumors in nude mice after administration of compound I at 40 mg / kg were significantly lower than those in the control group. Figure 5 D represents the change in body weight of nude mice during drug administration, represented by a line graph; after drug administration, orbital blood was collected from mice to detect the serum alanine aminotransferase (ALT) level. Figure 5 E) and aspartate aminotransferase (AST) Figure 5 The content of F) was measured to evaluate the hepatotoxicity of compound I in nude mice; serum creatinine levels were also measured. Figure 5 The content of G) was used to evaluate the nephrotoxicity of compound I in nude mice; by Figure 5 According to DG, compound I does not affect the weight of nude mice and has no hepatotoxicity or nephrotoxicity to nude mice.

[0131] In summary, compound I exhibits good in vivo anti-breast cancer activity, effectively inhibiting the growth of breast cancer cells in nude mice, without significantly affecting the weight and liver and kidney function of the mice.

[0132] It should be noted that the embodiments described above are only for explaining the present invention and do not constitute any limitation on the present invention. The present invention has been described with reference to typical embodiments, but it should be understood that the words used therein are descriptive and explanatory terms, not limiting terms. Modifications can be made to the present invention within the scope of the claims as specified, and revisions can be made to the present invention without departing from the scope and spirit of the present invention. Although the present invention described herein relates to specific methods, materials, and embodiments, it does not mean that the present invention is limited to the specific examples disclosed herein; on the contrary, the present invention extends to all other methods and applications with the same function.

Claims

1. Use of a compound targeting SND1 in the manufacture of a medicament for preventing and / or treating a disease mediated by SND1, wherein the compound targeting SND1 has the following structural formula: ###0001### and the disease mediated by SND1 is breast cancer, colorectal cancer, leukemia, esophageal cancer, pancreatic cancer, brain glioma, kidney cancer, skin cancer, osteosarcoma, ovarian cancer or prostate cancer mediated by SND1. ； 2. The use according to claim 1, wherein the compound targeting SND1 is a compound of the following structural formula: ###0002### 3. The use according to claim 1, wherein the compound targeting SND1 is a compound of the following structural formula: ###0003### 4. The use according to claim 1, wherein the compound targeting SND1 is a compound of the following structural formula: ###0004### 5. The use according to claim 1, wherein the compound targeting SND1 is a compound of the following structural formula: ###0005### 6. The use according to claim 1, wherein the compound targeting SND1 is a compound of the following structural formula: ###0006### 7. The use according to claim 1, wherein the compound targeting SND1 is a compound of the following structural formula: ###0007### 8. The use according to claim

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