Anti-tumor compound as well as preparation method and application thereof

Abstract

The invention provides an anti-tumor compound as well as a preparation method and application thereof. Related substances such as the compound disclosed by the invention have inhibitory activity on proliferation, migration and invasion of human triple negative breast cancer cell lines SUM159PT and MDA-MB-231, and can be prepared into an anti-tumor pharmaceutical composition together with a medicinal carrier and / or an excipient.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of pharmaceutical chemistry, in particular to an anti-tumor compound and a preparation method and application thereof. BACKGROUND

[0002] Breast cancer, as a malignant tumor seriously affecting the survival and life of women, is known as the first killer of women. Triple negative breast cancer (TNBC) refers to breast cancer with negative estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her-2), which is the most invasive subtype of breast cancer, accounting for about 20% of all breast cancers. At present, the diagnosis and treatment level of triple negative breast cancer is low, the treatment target is small, and more seriously, there are triple negative breast cancer stem cells (TCSCs) in tumor tissues. TNBC has special biological behavior and clinical pathological characteristics, such as small age of onset, strong invasiveness, high metastasis rate, low overall survival rate, poor prognosis and other characteristics. The unique pathological characteristics of triple negative breast cancer make it lack of therapeutic targets, resulting in extremely scarce drugs for treating TNBC.

[0003] It is very necessary to develop a drug for treating triple negative breast cancer with good curative effect. SUMMARY

[0004] The applicant found that chromosomal fragile site is a site-specific unstable region in normal genome, which is closely related to the occurrence and development of tumor. FATS gene is a high-frequency deletion region found in tumor genome, is a tumor suppressor gene related to DNA damage induced tumor, is located at 10q26.2, and is located on the chromosomal fragile site FRA10F. The expression of FATS gene can significantly induce the protein expression amount of p21, which is an important inhibitory factor for regulating cell cycle, so as to make the cell cycle arrest in G1 phase. FATS gene inhibits the deacetylation of HDAC 1 on p21 protein by protein interaction with histone deacetylase HDAC1, increases the stability and abundance of p21 protein in cells, and plays an important role in maintaining genome stability. FATS protein enhances the transcription factor activity and stability of p53 protein, and the expression of FATS protein in breast cancer samples is significantly reduced or silenced, indicating that the inactivation of FATS gene promotes the development of tumor. High expression of FATS can increase the radiotherapy sensitivity of breast cancer cells, and in patients receiving platinum combined chemotherapy, the prognosis of high expression of FATSmRNA is better than that of low expression, and FATS protein inhibits the occurrence and development of tumor. FATS targeted therapy is a precise treatment for the FATS gene on the surface of tumor cells, and it is extremely necessary to develop an effective anti-tumor drug which can enhance the expression level of FATS protein, increase the sensitivity of radiotherapy and chemotherapy drugs, and reduce potential adverse reactions. Based on this, the following contents are proposed:

[0005] The first application of the application is to provide a compound for enhancing the expression level of FATS protein or a pharmaceutically acceptable salt of the compound, which has the structure shown in the following formula (I):

[0006]

[0007] As an embodiment of the application, the pharmaceutically acceptable salt is an acid addition salt of the compound of formula (I), wherein the acid used for salification includes inorganic acid and organic acid, the inorganic acid includes hydrochloric acid, sulfuric acid, phosphoric acid and methanesulfonic acid, and the organic acid includes acetic acid, trichloroacetic acid, propionic acid, butyric acid, maleic acid, p-toluenesulfonic acid, malic acid, malonic acid, cinnamic acid, citric acid, fumaric acid, camphoric acid, digluconic acid, aspartic acid and tartaric acid.

[0008] The second application of the application is to provide a preparation method of the compound of formula (I) or the pharmaceutically acceptable salt of the compound, and the synthetic route is as follows:

[0009]

[0010] The third object of the present application is to provide an anti-tumor composition comprising the above-mentioned compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient. The carrier or excipient can be any commercially available product or a solution disclosed in the prior art.

[0011] As an embodiment of the present application, the dosage form of the anti-tumor composition includes oral preparations, injections, external preparations, or targeted preparations.

[0012] The fourth object of the present application is the use of the above-mentioned compound or a pharmaceutically acceptable salt thereof, or any of the above-mentioned anti-tumor compositions in the preparation of an inhibitor of the proliferation, migration, and invasion of triple-negative breast cancer cell lines SUM159PT and MDA-MB-231.

[0013] As an embodiment of the present application, the inhibitor has a specific binding site with FATSSer288.

[0014] The fourth object of the present application is the use of the above-mentioned compound or a pharmaceutically acceptable salt thereof, or any of the above-mentioned anti-tumor compositions in the preparation of an inhibitor of the proliferation, migration, and invasion of triple-negative breast cancer cell lines SUM159PT and MDA-MB-231.

[0015] As an embodiment of the present application, the inhibitor has a specific binding site with FATSSer288.

[0016] The disclosed compound and related substances have inhibitory activity on the proliferation, migration, and invasion of human triple-negative breast cancer cell lines SUM159PT and MDA-MB-231, and can be prepared into an anti-tumor pharmaceutical composition with a pharmaceutical carrier and / or excipient. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 Schematic diagram of the binding mode of different compounds with FATS protein.

[0018] Figure 2 Detection of the cytotoxicity of different compounds on SUM159PT and MDA-MB-231 cell lines.

[0019] Figure 3 Schematic diagram of the inhibition of the proliferation, migration, and invasion of SUM159PT and MDA-MB-231 cells and the wound healing ability of the cells.

[0020] Figure 4 Schematic diagram of the mouse safety experiment.

[0021] Figure 5 Schematic diagram of the specific binding with FATS Ser288 site. DETAILED DESCRIPTION

[0022] In order to make the purposes, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be described clearly and completely below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only some of the embodiments of the present application, but not all the embodiments. Unless defined, the technical terms used in the following embodiments have the same meanings as commonly understood by those skilled in the art to which the present application belongs. The test reagents used in the following embodiments are all conventional biochemical reagents, unless otherwise specified. The experimental methods described, unless otherwise specified, are conventional methods.

[0023] The test materials used in the following embodiments, unless otherwise specified, are all purchased from conventional biochemical reagent stores. The present application will be described in detail below with reference to specific embodiments.

[0024] I. Experimental content

[0025] The structural formulas of CP4, CP4-M14 and CP4-M2 appearing in the experimental process are as follows, respectively:

[0026] The structural formula of CP4 is:

[0027]

[0028] The structural formula of CP4-M14 is:

[0029]

[0030] The structural formula of CP4-M2 is:

[0031]

[0032] 1. Taking compounds CP4-M14 and CP4-M2, study the binding ability of different compounds to FATS protein

[0033] As shown in Figure 1 , the binding mode of compounds CP4-M14 and CP4-M2 to FATS protein. The cytotoxicity of CP4-M14 and CP4-M2 to SUM159PT and MDA-MB-231 cell lines was detected, and their IC50 was determined, as shown in Figure 2 . The results show that the IC50 value of CP4-M2 is significantly lower than that of CP4-M14, indicating that the inhibitory effect of CP4-M2 on the two cell lines is stronger than that of CP4-M14, and the chemical structure of CP4-M2 is more suitable for binding to FATS protein, and CP4-M2 is determined as the most suitable compound.

[0034] 2. Blank group, CP4 and CP4-M2 group were used for inhibition effect experiment

[0035] 1) Cell activity test: SUM159PT and MDA-MB-231 cells were cultured to a density of 80% at 37°C, 5% CO2 incubator. The cells were divided into three groups, one group was added with DMSO as a control group, one group was added with compound CP4, and the third group was added with compound CP4-M2, corresponding to the three groups of WT+DMSO, WT+CP4 and WT+M2.

[0036] Cell viability assay: a. Count the number of cells in the prepared cell suspension with a cell counting plate, then inoculate the cells; b. Dilute the medium in proportion to form a cell concentration gradient, 5 cell concentration gradients, 5 replicate wells in each group; c. Incubate for 4 hours after inoculation to allow the cells to adhere, then add 10 μL CCK-8 reagent per 100 μL medium and incubate for 1.5 h before measuring the OD value, and a standard curve is made with cell number as the horizontal coordinate and OD value as the vertical coordinate.

[0037] Cell activity test: a. Inoculate cell suspension (100 μL / well) in a 96-well plate, and place the culture plate in the incubator for 24 hours of pre-culture; b. Add 10 μL of CCK-8 solution to each well; c. Incubate the culture plate in the incubator for 4 hours; d. Measure the absorbance at 450 nm with a microplate reader. Record the OD value at 0 hours, 24 hours, 48 hours and 72 hours. Statistical analysis of the collected data to calculate the percentage of cell viability of each treatment group at each time point.

[0038] The experimental results are shown in Figure 3 After 72 hours of culture, the cell viability of the WT+CP4 and WT+DMSO groups was significantly higher than that of the WT+M2 group. It is shown that compound CP4-M2 significantly inhibits the proliferation of SUM159PT and MDA-MB-231 cells, and the inhibitory effect is better than that of compound CP4.

[0039] 2) Colony formation assay: SUM159PT and MDA-MB-231 cells in log phase were trypsinized and blown into single cells, and the cells were suspended in complete medium for use. The cell suspension was diluted in gradient multiples, 5 parallel samples in each group. 100 cells in each group were inoculated in each dish containing 10 ml of pre-warmed culture solution at 37°C, and gently rotated to disperse the cells evenly. The culture dishes were placed in a cell incubator at 37°C, 5% CO2 for 2 weeks. When visible colonies appeared in the culture dishes, the culture was terminated. The supernatant was discarded and washed with PBS twice. Add 5 ml of pure methanol or 1:3 acetic acid / methanol, fix for 15 minutes. Add an appropriate amount of Giemsa staining solution, and stain for 30 minutes. Slowly wash off the staining solution with running water, and air dry. Invert the dish and overlay a transparent film with a grid, and use ImageJ to calculate the colony area and calculate the colony formation rate. Colony formation rate = (colony area / total area) x 100%. The results are shown in Figure 3 Figure 2, indicating that compound CP4-M2 significantly inhibited the proliferation of cells and the inhibitory effect was better than that of compound CP4.

[0040] 3) Transwell experiment: To detect the effect of compound CP4-M2 on the migration and invasion ability of SUM159PT and MDA-MB-231 cells.

[0041] Experimental procedure: Matrigel was diluted 1:8 with serum-free cell culture medium or PBS buffer at 4°C. 60 μΐ was added to the upper chamber of the Transwell chamber and incubated for 3 h at 37°C to allow the Matrigel to polymerize into a thin film. After incubation, the excess liquid was removed from the upper chamber and 100 μΐ of serum-free medium was added to each well. The wells were then incubated for 30 min at 37°C to hydrate the basement membrane. Cells were harvested at the logarithmic growth phase, trypsinized for 2 min at 1000 rpm, and then centrifuged for 3 min. The supernatant was discarded and the cells were washed twice with PBS. The cells were then resuspended in serum-free medium and adjusted to a concentration of 100,000 cells / mL. 500 μΐ of medium containing 10% FBS was added to the lower chamber of a 24-well plate, and the Transwell chamber was then placed in the 24-well plate using tweezers. 100 μΐ of the cell suspension was added to the upper chamber, and the plate was then incubated for 24 h at 37°C. The Transwell chamber was carefully removed, and the medium in the upper chamber was removed using a cotton swab. The cells on the Matrigel and the upper chamber were gently scraped using a cotton swab. A new 24-well plate was prepared by adding 600 μΐ of 4% paraformaldehyde, and the Transwell chamber was then placed in the plate for 30 min to fix the cells. After removing the fixing solution from the upper chamber, the chamber was transferred to a well containing 800 μΐ of 0.1% crystal violet dye, and the cells were dyed for 20 min. The crystal violet that was not bound to the cells was removed by gently wiping the upper side of the chamber with a cotton swab. The chamber was then washed several times with water, and the liquid in the upper chamber was then removed by suction. The cells on the bottom membrane of the upper chamber were carefully scraped using a wet cotton swab. The membrane was carefully removed using tweezers, and the bottom surface was oriented upwards. The membrane was allowed to air dry for an appropriate amount of time. The membrane was then transferred to a glass slide and mounted using neutral balsam. The membrane was observed and photographed under a high-power microscope, and 5 fields of view (including one each of the top, bottom, center, left, and right) were randomly selected. The number of purple positive cells was counted, and the results were finally calculated. The experimental results are shown in Figure 3 Figure 1. The number of migrating and invading cells in the WT+M2 group was significantly reduced compared to the WT+DMSO group and the WT+CP4 group, indicating that the compound CP4-M2 significantly inhibited the migration and invasion of SUM159PT and MDA-MB-231 cells, and the effect was better than that of CP4.

[0042] 4) Cell scratch test:

[0043] (1) Cell treatment and plating: The cells were evenly plated in a 6-well plate at a confluence of about 50%, and then incubated in a culture incubator overnight. The number of cells in the experimental and control groups should not differ greatly at the time of inoculation. The scratch test was performed when the 6-well plate was fully covered with cells.

[0044] (2) Scratch: Draw a horizontal line on the bottom of the 6-well plate with a white 10 μl pipette tip and a ruler, and make sure the force is uniform throughout the process.

[0045] (3) Collect pictures, analyze data: Discard the culture solution, wash with 1xPBS solution for 2-3 times, use a pipette to suck the empty original culture solution into the 6-well plate, and then put it into the incubator for further culture. Collect images at 0h and 24h of culture, and analyze data with Photoshop.

[0046] Then perform the clone formation experiment, transwell experiment, and cell scratch experiment, as shown in Figure 3 The results show that the cell viability of the WT+M2 group decreases significantly, the number of cells migrating and invading is significantly reduced compared with the WT+DMSO group and the WT+CP4 group, and the scratch area is reduced less. It shows that the compound CP4-M2 significantly inhibits the proliferation, migration, invasion ability and wound healing ability of SUM159PT and MDA-MB-231 cells, and the inhibition effect is better than CP4.

[0047] Use WT+DMSO, WT+CP4, WT+M2 three different treatment conditions to perform CCK8 experiment, clone formation experiment, transwell experiment, and cell scratch experiment on SUM159PT and MDA-MB-231 cell lines, as shown in Figure 3 The results show that the cell viability of the WT+M2 group decreases significantly, the number of cells migrating and invading is significantly reduced compared with the WT+DMSO group and the WT+CP4 group, and the scratch area is reduced less. It shows that the compound CP4-M2 significantly inhibits the proliferation, migration, invasion ability and wound healing ability of SUM159PT and MDA-MB-231 cells, and the inhibition effect is better than CP4.

[0048] 3. Mouse experiment

[0049] The nude mouse research plan is approved by the Animal Ethics Committee of Tianjin Medical University Cancer Hospital. The feeding and experimental procedures of mice comply with relevant guidelines at home and abroad. Female nude mice (4 weeks old) are purchased from Jiangsu Jizhuangkang Biotechnology Co., Ltd. MDA-MB-231 cells are suspended in PBS and mixed with Matrigel (REF354234, Corning, USA) before being injected subcutaneously into mice. After tumor formation, mice are treated with 5mg / kg paclitaxel (GlpBio, USA). Monitor body weight and tumor volume, collect tumor tissue for analysis and histopathological examination.

[0050] As shown in Figure 4As shown, CP4-M2 was injected intraperitoneally into C57BL / 6 mice, and the effects of CP4-M2 on tumor weight and volume at different time points were monitored. Hepatotoxicity, nephrotoxicity, and changes in blood cell count were also examined. The results showed that CP4-M2 significantly reduced tumor weight and volume, and kept all biological indicators within safe ranges. HE and immunohistochemistry showed that CP4-M2 did not cause significant histological changes in the heart, liver, spleen, lungs, and kidneys of mice, demonstrating the drug's safety.

[0051] 4. Binding characteristics with the Ser288 site of the FATS gene

[0052] like Figure 5 As shown, the Ser288 site of the FATS gene was mutated to Ala. The mutated FATS gene was named FATS-MT. After this mutation, FATS cannot bind to CP4-M2. The wild-type FATS gene was named FATS-WT. SUM159PT and MDA-MB-231 cell lines containing FATS-WT and FATS-MT were subjected to CCK8 assays, colony formation assays, transwell assays, and cell scratch assays, respectively, using the methods disclosed in the above-mentioned inhibitory effect experiments. The results showed that after the point mutation of the FATS gene, the inhibitory ability of CP4-M2 on cell proliferation, migration, invasion, and cell wound healing was significantly reduced. This indicates that the inhibitory function of compound CP4-M2 on tumor cells is based on binding to the FATSSer288 site, proving that CP4-M2 exerts its anti-tumor effect through specific binding to FATSSer288.

[0053] II. Preparation of compounds with the structure shown in CP4-M2

[0054] CP4-M2 is abbreviated as Formula (I):

[0055]

[0056] 1. Synthetic route

[0057]

[0058] 2. Synthesis Steps

[0059] The following is an exemplary synthesis method, which can be adapted to the synthetic route, such as adjusting the amount of raw materials, reaction conditions, and types of excipients. A method for preparing small doses is also provided below:

[0060] 1) Step 1:

[0061] 3,3'-(propane-1,3-diyl)bis(2-thioxo-2,

[0062] 3-dihydroquinazolin-4(1H)-one)

[0063] 2-isothiocyanatobenzoic acid methyl ester (4.2 g, 21.64 mmol) was dissolved in 1,4-dioxane (40 mL), triethylamine (3.36 g, 43.30 mmol), 1,3-diaminopropane (0.55 g, 7.43 mmol) was added and heated to 100 °C in air for 16 h. Dichloromethane (30 ml) was added and then filtered to get yellow solid 3,3'-(propane-1,3-diyl)bis(2-thioxo-2,

[0064] 3-dihydroquinazolin-4(1H)-one) (2.5 g, 85.03 % yield).

[0065] 2) Step 2:

[0066] 3-(3-methoxyphenyl)-1-(p-tolyl)-1H-pyrazol-5-amine

[0067] 3-methoxybenzoyl acetonitrile (3 g, 17.14 mmol) was dissolved in 30 ml of ethanol, 1-(p-tolyl)-1H-pyrazol-5-amine (2.71 g, 17.14 mmol) and sodium acetate (2.81 g, 34.28 mmol) were added and then refluxed at 80 °C for 5 h. The reaction was quenched with 20 ml of saturated brine and then extracted with 50 ml of ethyl acetate three times. The organic phase was combined, dried over anhydrous sodium sulfate overnight and then concentrated to get the crude product. The crude product was purified by column chromatography PE:EtOAc (5:1) to get the white solid product 3-(3-methoxyphenyl)-1-(p-tolyl)-1H-pyrazol-5-amine (4 g, 83.65 % yield).

[0068] 3) Step 3:

[0069] 2-chloro-N-(3-(3-methoxyphenyl)-1-(p-tolyl)-1H-pyrazol-5-yl)acetamide

[0070] 4-(3-methoxyphenyl)-l-(p-tolyl)-lH-pyrazol-5-amine (2g, 7.17 mmol) and triethylamine (2.17g, 21.42 mmol) were dissolved in 20 ml of dichloromethane and the reaction was cooled to 0 °C in an ice bath. 2-Chloroacetyl chloride (2g, 18.02 mmol) was added dropwise via a constant pressure dropping funnel. The reaction was maintained at 0 °C for 1 h and upon completion, quenched with 20 ml of saturated brine and extracted with 50 ml of ethyl acetate three times. The organic phases were combined and dried over anhydrous sodium sulfate overnight and concentrated to yield a crude product which was purified by column chromatography using PE:EtOAc (2: 1) to yield the product as a yellow oil.

[0071] 2-chloro-N-(3-(3-methoxyphenyl)-l-(p-tolyl)-lH-pyrazol-5-yl)acetamide (1.7g, 83.65% yield) MS: m / z = 356.2 (M+l, ESI+).

[0072] 4) Step 4:

[0073] 2,2'-((propane-l,3-diylbis(4-oxo-3,4-dihydroquinazoline-3,2-diyl))bis(sulfanediyl))bis(N-(3-(3-methoxyphenyl)-l-(p-tolyl)-lH-pyrazol-5-yl)acetamide)

[0074] 2-chloro-N-(3-(3-methoxyphenyl)-l-(p-tolyl)-lH-pyrazol-5-yl)acetamide (355mg, 1mmol) and 3,3'-(propane-l,3-diyl)bis(2-thioxo-2,3-dihydroquinazolin-4(lH)-one) (200mg, 0.51mmol) were dissolved in 2 ml of N,N-dimethylformamide and K2CO3 (210mg, 1.53mmol) was added. The reaction was stirred at room temperature for 5 h and upon completion, quenched with 10 ml of saturated brine and extracted with 20 ml of ethyl acetate twice. The organic phases were combined and dried over anhydrous sodium sulfate overnight and concentrated to yield a crude product which was purified by column chromatography using DCM:MeOH (30: 1) to yield an intermediate product which was further purified by preparative high performance liquid chromatography to yield the product as a yellow solid 2,2'-((propane-l,3-diylbis(4-oxo-3,4-dihydroquinazoline-3,

[0075] 2-diyl))bis(sulfanediyl))bis(N-(3-(3-methoxyphenyl)-1-(p-tolyl)-1H-pyrazol-5-yl)acetamide)(30 mg, 6.3% yield) 1H NMR (400 MHz, DMSO-d6) δ: 10.29 (s, 2H), 8.06 (d, 2H), 7.75-7.73 (m, 2H), 7.47-7.29 (m, 14H), 7.09-7.07 (m, 4H), 6.90-6.85 (m, 4H), 4.23-4.19 (m, 8H), 3.78 (s, 6H), 2.23 (s, 8H). MS: m / z = 1035.1 (M+l, ESI+).

[0076] Based on the anti-tumor properties of CP4-M2, i.e., the compound of formula (I), an anti-tumor composition is further provided, which contains the above-mentioned compound or a pharmaceutically acceptable salt of the compound, and a pharmaceutically acceptable carrier or excipient. The carrier or excipient can be selected from any commercially available product or the scheme disclosed in the prior art. Specifically, one of the optional schemes. The carrier or excipient of the present application is a pharmaceutically acceptable carrier or excipient, which refers to one or more compatible solid or liquid fillers or gel materials. They are suitable for human use, and must have sufficient purity and sufficiently low toxicity. "Compatibility" here refers to the ability of the components in the composition to mix with the active ingredient of the present application and among themselves without significantly reducing the efficacy of the active ingredient. The carrier includes but is not limited to: diluents, buffers, suspensions, emulsions, granules, encapsulations, excipients, fillers, binders, sprays, transdermal absorption agents, humectants, disintegrants, absorption promoters, surfactants, colorants, flavorings or adsorption carriers.

[0077] Further, in the selection of dosage forms, the above-mentioned drugs can be made into any medically available dosage form as needed. Including oral preparations, injections, topical preparations or targeted preparations, such as oral liquids, tablets, capsules, injection solutions, liniments, targeted drugs, etc.

[0078] The above examples are only used to illustrate the technical solutions of the present application, but not to limit it; although the application has been described in detail with reference to the foregoing examples, those skilled in the art should understand that they can still modify the technical solutions recorded in the foregoing examples, or make equivalent substitutions for part of the technical features; and these modifications or substitutions do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present application.

Claims

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof, characterized in that, The structure of equation (Ⅰ) is as follows:

2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The pharmaceutically acceptable salt is an acid addition salt of a compound of formula (I), wherein the acid used for salt formation includes inorganic acids and organic acids, wherein the inorganic acids include hydrochloric acid, sulfuric acid, phosphoric acid and methanesulfonic acid, and the organic acids include acetic acid, trichloroacetic acid, propionic acid, butyric acid, maleic acid, p-toluenesulfonic acid, malic acid, malonic acid, cinnamic acid, citric acid, fumaric acid, camphoric acid, digluconic acid, aspartic acid and tartaric acid.

3. A method for preparing a compound or a pharmaceutically acceptable salt thereof, characterized in that, The synthetic route is as follows: The compound is selected from any one of claims 1-2 or a pharmaceutically acceptable salt of the compound.

4. An antitumor composition, characterized in that, The composition contains any one of the compounds of claims 1-2 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

5. The antitumor composition according to claim 4, characterized in that, The dosage forms of the antitumor composition include oral formulations, injections, topical formulations, or targeted formulations.

6. Use of the compound of any one of claims 1-2 or a pharmaceutically acceptable salt thereof, or the antitumor composition of any one of claims 4-5, in the preparation of inhibitors of proliferation, migration, and invasion of triple-negative breast cancer cell lines SUM159PT and MDA-MB-231.

7. The application according to claim 6, characterized in that, The inhibitor has a specific binding site for FATSSer288.

8. The use of the compound of any one of claims 1-2 or a pharmaceutically acceptable salt thereof, or the antitumor composition of any one of claims 4-5, in the preparation of a medicament for treating breast cancer.

9. The application according to claim 8, characterized in that, The drug exerts its anti-tumor effect by stimulating the activity of the FATS protein.

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