Application of PGK1 inhibitor in preparation of medicine for treating endometrial tumor and ovarian tumor

Abstract

The invention discloses application of a PGK1 inhibitor in preparation of a medicine for treating endometrial tumor and ovarian tumor and a medicinal composition containing the PGK1 inhibitor. The pharmaceutical composition containing the PGK1 inhibitor is a targeted drug, has a significant inhibition effect on endometrial tumors and ovarian tumors, and is small in side effect and clear in drug action site.

Description

Technical Field

[0001] The present invention relates to anti-tumor drugs, in particular to use of a PGK1 inhibitor in preparing drugs for treating endometrial tumors and ovarian tumors. Background Art

[0002] Endometrial cancer is one of the three major gynecological malignancies. Clinical data from the United States show that there were 49,560 new cases of endometrial cancer in 2013, 63,230 new cases in 2018, and about 65,950 new cases of uterine cancer in 2022, with about 12,550 deaths. It is expected that the number of new cases will increase to 130,000 in 2030.

[0003] The treatment of endometrial cancer is mainly surgical resection, supplemented by radiotherapy and drug therapy. For patients with estrogen-dependent and infertile early-stage endometrial cancer, progesterone is often used for conservative treatment to preserve fertility; for advanced patients, appropriate chemotherapy should be taken before surgery to reduce the size of the tumor, and the rational selection of chemotherapy drugs can significantly improve the surgical resection rate; for metastatic endometrial cancer and postoperative recurrent endometrial cancer, currently commonly used are hormone drugs such as progesterone, gonadotropin-releasing hormone analogs, aromatase inhibitors, and chemotherapy drugs such as paclitaxel, carboplatin, cisplatin, and doxorubicin, and chemotherapy resistance is the main problem faced clinically.

[0004] With the discovery of more and more therapeutic targets for endometrial cancer, targeted therapy has also made significant breakthroughs, especially for advanced and recurrent endometrial cancer. The therapeutic targets currently being studied include: epidermal growth factor receptor antagonists, vascular endothelial growth factor targeted inhibitors, PI3K / Akt / mTOR pathway inhibitors, programmed cell death protein 1 inhibitors, epigenetic modification inhibitors, PARP inhibitors, etc. However, targeted therapy is not widely used in the clinical application of endometrial cancer, and most targeted inhibitors are still in the clinical trial stage.

[0005] Ovarian cancer is the third most common gynecological cancer in my country, and its mortality rate ranks first. Due to the lack of obvious early symptoms of ovarian cancer and the lack of accurate clinical diagnostic methods, patients diagnosed with ovarian cancer are often already in the late stage, with a low 5-year survival rate. The treatment of ovarian cancer is usually based on chemotherapy with platinum drugs and paclitaxel. Patients respond well to this type of chemotherapy, but the specificity of chemotherapy drugs is not high, and drug resistance has become a key obstacle to the treatment of ovarian cancer. In recent years, more and more gene targets have been confirmed to be closely related to ovarian cancer, and targeted therapy for ovarian cancer has also achieved excellent results in clinical practice.

[0006] The latest research shows that the occurrence and development of tumors are closely related to the glycolysis pathway. The transformation of normal cells into malignant tumor cells is accompanied by the remodeling of metabolic pathways. Abnormal glucose metabolism is an important feature of tumor cells. Most normal cells obtain energy by breaking down glucose through aerobic oxidation in the presence of oxygen, and glycolysis only occurs in hypoxia. In malignant tumors, the proliferation rate of tumor cells exceeds their energy supply, so the excessive consumption of oxygen and nutrients by cells can lead to a tumor microenvironment with low oxygen, low sugar and acidity, which is more obvious in solid tumors. The main way to enhance tumor cell glycolysis is to adjust glycolytic enzymes to enhance their activity and overexpress them. Studies have found that by inhibiting glycolysis, anti-tumor effects can be achieved, and the purpose of inhibiting tumor cell proliferation and killing tumor cells can be achieved. Phosphoglycerate kinase 1 (PGK1), lactate dehydrogenase A (LDHA), and pyruvate kinase 2 (PKM2) are all key enzymes in the glycolysis process. PGK1 significantly upregulates its expression in a variety of malignant tumors such as liver cancer, colon cancer, and neuroblastoma. However, the role of PGK1 in endometrial cancer is still unknown. Some literature reports that PGK1 is related to the occurrence of endometrial cancer (Suiqun Guo, Yanyi Xiao, Danqing Li, Qingping Jiang, Litong Zhu, Dan Lin, Huiping Jiang, Wei Chen, Lijing Wang, Chunhua Liu, Weiyi Fang, Li Lin. PGK1 and GRP78 overexpression correlates with clinical significance and poor prognosis in Chinese endometrial cancer patients. Oncotarget. 2017, 9(1): 680-690.). There are also reports that it has a significant relationship with the occurrence of ovarian cancer (Jiawen Zhang, Jing Zhang, Yingze Wei, Qingxian Li, Qingying Wang. ACTL6A regulates follicle-stimulating hormone-driven glycolysis in ovarian cancer cells via PGK1. Cell Death Dis. 2019, 10(11): 811.) The effect of PGK1 inhibitors on endometrial cancer and ovarian cancer is still unknown.

[0007] NG52 is a potent, selective, ATP-compatible and orally active inhibitor of Cdc28p and Pho85p kinases. 50The value is 2.5μM to inhibit the activity of phosphoglycerate kinase 1 (PGK1). In animal studies, the PGK1 inhibitor NG52 was found to have less toxic side effects. The body weight of the animals after administration was not statistically different from that of the negative control group. It also had a significant inhibitory effect on endometrial cancer transplants and ovarian cancer strains. Therefore, it may become a new type of therapeutic drug targeting endometrial cancer and ovarian cancer.

[0008] The chemical name of NG52 is 2-[[6-[(3-chlorophenyl)amino]-9-isopropyl-9H-purin-2-yl]amino]ethanol, and it has the following structural formula:

[0009]

[0010] Through experiments, we found that the PGK1 inhibitor NG52 has a good inhibitory effect on three types of endometrial cancer and one type of ovarian cancer, and this effect has not yet been reported in domestic and foreign literature and patents. Summary of the invention

[0011] Technical Problems to be Solved by the Invention

[0012] The hormone therapy in the existing treatment of endometrial cancer and ovarian cancer may cause side effects such as water and sodium retention, thrombosis or drug-induced hepatitis when used for a long time. The side effects of chemotherapy for endometrial cancer and ovarian cancer are as follows: 1. Bone marrow suppression. Bone marrow suppression is manifested as a decrease in white blood cells, a decrease in neutrophils, a decrease in red blood cells, and anemia; 2. Nausea and vomiting. Severe nausea, vomiting, and hair loss. 3. Blood vessels will harden, also known as chemotherapy vasculitis. In addition, chemotherapy resistance is also a major problem faced clinically.

[0013] Since there is no effective targeted drug for treating endometrial cancer and ovarian cancer, the purpose of the present invention is to provide a new targeted drug for treating endometrial cancer and ovarian cancer. The targeted drug of the present invention has the advantages of small side effects and clear drug action site.

[0014] Technical solutions to technical issues

[0015] In order to determine the inhibitory effect of PGK1 inhibitor NG52 on endometrial cancer and ovarian cancer, the present invention adopts tumor cells and nude mouse transplanted tumor models to detect the effect of PGK1 inhibitor NG52.

[0016] Specifically, the present invention includes the following technical solutions.

[0017] The present invention includes the use of a PGK1 inhibitor NG52 or a pharmaceutically acceptable salt thereof in preparing a drug for treating endometrial tumors.

[0018] In the present invention, the endometrial tumor is endometrial cancer.

[0019] In the present invention, the endometrial cancer may be, for example, adenocarcinoma, carcinosarcoma, squamous cell carcinoma, undifferentiated carcinoma, small cell carcinoma and transitional carcinoma.

[0020] In the present invention, the endometrial tumor or endometrial cancer is caused by the Ishikawa cell line, the HEC-1-A cell line or the HEC-1-B cell line.

[0021] The present invention also includes a composition for treating endometrial tumors, the composition comprising PGK-1 inhibitor NG52 or a pharmaceutically acceptable salt thereof, and optionally one or more pharmaceutically acceptable carriers.

[0022] The composition of the present invention preferably further contains paclitaxel or a pharmaceutically acceptable salt thereof, and / or one or more active ingredients other than paclitaxel for treating endometrial tumors.

[0023] The active ingredient can be, for example, a progestin (e.g., medroxyprogesterone, progesterone caproate, megestrol acetate), an anti-estrogen preparation (e.g., tamoxifen), an aromatase inhibitor (e.g., raloxifene), or (1S, 2S, 3S, 5R)-3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol disclosed in patent application TW202128176A.

[0024] The present invention also provides use of a PGK1 inhibitor NG52 or a pharmaceutically acceptable salt thereof in preparing a drug for treating ovarian tumors.

[0025] Wherein, the ovarian tumor is ovarian cancer, and the ovarian cancer is caused by Ovcar-3 cell line.

[0026] The present invention also provides a composition for treating ovarian tumors, which contains a PGK-1 inhibitor NG52 or a pharmaceutically acceptable salt thereof, and one or more active ingredients for treating ovarian tumors other than the above-mentioned NG52 or a pharmaceutically acceptable salt thereof.

[0027] In the present invention, the pharmaceutically acceptable salt thereof is preferably an acid addition salt formed with an inorganic acid or an acid addition salt formed with an organic acid.

[0028] The present invention also provides a method for treating endometrial tumors and / or ovarian tumors, which comprises administering a therapeutically effective amount of NG52 to a patient in need thereof.

[0029] Beneficial technical effects

[0030] Compared with existing endometrial and ovarian cancer treatment drugs, the PGK1 inhibitor NG52 has a significant inhibitory effect on endometrial cancer and ovarian cancer, does not produce drug resistance, and has fewer side effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 . A graph showing the inhibitory effects of NG52 and paclitaxel alone and in combination on the endometrial cancer cell line Ishikawa.

[0032] Figure 2 .Growth curve of Ishikawa cell transplanted tumor after drug action.

[0033] Figure 3 .The curve of body weight changes of nude mice during drug administration.

[0034] Figure 4 .Cell survival rate of ovarian cancer Ovcar-3 cell line under the action of different concentrations of NG52. DETAILED DESCRIPTION

[0035] definition

[0036] To facilitate the understanding of the present invention, certain terms and phrases are defined and explained below.

[0037] As used herein, the term "inhibitor" refers to any molecule that partially or completely blocks, inhibits, reduces or neutralizes a target biological activity and / or signaling pathway.

[0038]

[00136] As used herein, the terms "cancer" and "cancerous" refer to or describe the physiological condition in which a population of cells in mammals is characterized by unregulated cell growth.

[0039] As used herein, the terms "tumor" and "neoplasm" refer to any mass of tissue resulting from excessive cell growth or proliferation, either benign (noncancerous) or malignant (cancerous), including precancerous lesions.

[0040] As used herein, the terms "cancer cell" and "tumor cell" refer to the total population of cells derived from cancer or a tumor or precancerous lesions (including non-tumorigenic cells), which includes a large population of cancer cells and tumorigenic stem cells (cancer stem cells).

[0041] The term "pharmaceutically acceptable" refers to products or compounds approved by the national drug regulatory authorities or listed in the Chinese Pharmacopoeia or other recognized pharmacopoeias for use in animals including humans.

[0042] The terms "treat" and "alleviate" refer to therapeutic measures that cure, slow down, alleviate the symptoms of a diagnosed case condition or disease and / or stop its progression, and therefore, subjects / patients in need of treatment include subjects / patients who already have the disease. In certain embodiments, a subject / patient of the methods described herein is successfully "treated" if the subject / patient shows one or more of the following: a reduction in the number of tumor cells or the complete absence of the tumor; a reduction in tumor size; inhibition or absence of cancer cell infiltration into surrounding organs (including tumor cell spread into soft tissue and bone); inhibition or absence of tumor or cancer cell metastasis; inhibition or absence of cancer growth; alleviation of one or more symptoms associated with a particular cancer; reduction in morbidity and mortality; improvement in quality of life; reduction in tumorigenicity; reduction in the number or frequency of cancer stem cells; or some combination of the effects.

[0043] The term "endometrial cancer" refers to any cancer that develops in the inner lining of the uterus. Endometrial cancer includes, for example, adenocarcinoma, carcinosarcoma, squamous cell carcinoma, undifferentiated carcinoma, small cell carcinoma, and transitional carcinoma, of which adenocarcinoma is the most common.

[0044] The term "ovarian cancer" is a type of ovarian tumor, which refers to a malignant tumor that grows on the ovaries.

[0045] As used in the specification and claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0046] The terms "above", "below" and "within" herein include the number unless the context clearly dictates otherwise.

[0047] It should be understood that when the embodiments are described herein as "comprising" or "containing", other similar embodiments described as "consisting of" and / or "consisting essentially of" are also provided. It should also be understood that when the embodiments are described herein as "consisting essentially of", other similar embodiments described as "consisting of" are also provided.

[0048] The term "and / or" as used herein in phrases such as "A and / or B" is intended to include both A and B; A or B; A (alone); and B (alone). Similarly, the term "and / or" as used in phrases such as "A, B, and / or C" is intended to include each of the following embodiments: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[0049] As used herein, "pharmaceutically acceptable carrier" refers to a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, or solvent encapsulating material, which participates in carrying or transporting the active compound from one organ or part of the body to another organ or part of the body. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Some examples of materials that can be used as pharmaceutically acceptable carriers include, but are not limited to: sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethylcellulose, ethylcellulose, and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols such as propylene glycol; polyols such as glycerol, sorbitol, mannitol, and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffers such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethanol; pH buffered solutions; polyesters, polycarbonates, and / or polyanhydrides; and other nontoxic compatible substances used in pharmaceutical formulations.

[0050] As used herein, "pharmaceutically acceptable salts" are pharmaceutically acceptable organic or inorganic acid or base salts of the compounds described herein. Pharmaceutically acceptable salts of the compounds of the present invention may be, for example, acid addition salts of compounds of the present invention carrying nitrogen atoms in the chain or ring, for example, acid addition salts of sufficiently basic compounds of the present invention, for example, acid addition salts formed with inorganic acids, for example, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, bisulfuric acid, phosphoric acid or nitric acid, or acid addition salts formed with organic acids, for example, formic acid, acetic acid, acetoacetic acid, pyruvic acid, trifluoroacetic acid, propionic acid, butyric acid, hexanoic acid, heptanoic acid, undecanoic acid, lauric acid, benzoic acid, salicylic acid, 2-(4-hydroxybenzoyl)-benzoic acid, camphoric acid, cinnamic acid, cyclopentane acid, digluconic acid, 3-hydroxy-2-naphthoic acid, nicotinic acid, pamoic acid, pectinic acid, persulfuric acid, 3-phenylpropionic acid, picric acid, pivalic acid, 2-hydroxyethanesulfonic acid, itaconic acid, sulfamic acid, trifluoromethanesulfonic acid, dodecylsulfuric acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, 2-naphthalenesulfonic acid, naphthalenedisulfonic acid, camphorsulfonic acid, citric acid, tartaric acid, stearic acid, lactic acid, oxalic acid, malonic acid, succinic acid, malic acid, adipic acid, maleic acid, fumaric acid, D-gluconic acid, mandelic acid, ascorbic acid, glucoheptonic acid, glycerophosphoric acid, aspartic acid, sulfosalicylic acid, hemisulfuric acid or thiocyanic acid.

[0051] Example

[0052] The present invention is described in detail below with reference to the following examples. The examples provide detailed implementation methods and processes to fully disclose and demonstrate that the invention can be implemented. The examples do not represent limitations on the invention, and the protection scope of the present invention is not limited to the following examples.

[0053] The instruments, reagents, materials, experimental animals, etc. whose sources are not specified in the examples of the specification are purchased through general commercial channels. The experimental methods without specific conditions in the examples of the specification are usually carried out according to the conventional conditions in the field or the conditions recommended by the manufacturer.

[0054] Example 1: Inhibitory effect of NG52 on three endometrial cancer cell lines

[0055] Ishikawa cells or HEC-1-A and HEC-1-B cells in the logarithmic growth phase were digested with 0.25% trypsin to obtain 1×10 5 / ml, and 1×10 4 Each well was inoculated in a 96-well plate, 100 μl per well, and 3 replicates were set up in each group. The cells were placed in a 5% CO2, 37°C incubator for culture. After the cells adhered to the wall, different concentrations of NG52 and paclitaxel were added. The final concentrations of NG52 in Ishikawa cells were 50, 25, 12.5, 6.25, 3.13, 1.56, 0.78, and 0.39 μM, and the final concentrations of paclitaxel were 25, 12.5, 6.25, 3.13, 1.56, 0.78, 0.39, and 0.20 nM, respectively. The final concentrations of NG52 in HEC-1-A and HEC-1-B cells were 100, 50, 25, 12.5, 6.25, 3.13, 1.56, and 0.78 μM, respectively, and the final concentrations of paclitaxel were 100, 50, 25, 12.5, 6.25, 3.13, 1.56, and 0.78 nM, respectively. After 72 hours of drug exposure, 10 μl of CCK-8 solution was added to each well and cultured continuously. After 2 hours, the absorbance of each well at a wavelength of 450 nm was detected and calculated using an ELISA reader to calculate the IC 50 , the experimental results are shown in Table 1.

[0056] Table 1: IC of NG52 and Paclitaxel in Ishikawa, HEC-1-A and HEC-1-B cells 50

[0057]

[0058] The experimental results showed that NG52 had a good inhibitory effect on the growth of endometrial cancer cell lines Ishikawa, HEC-1-A and HEC-1-B. 50 They are 18.26μM, 35.70μM and 29.11μM respectively.

[0059] Example 2: Detection of the inhibitory effect of combined administration of NG52 and paclitaxel on tumor cells

[0060] On the basis of single drug, NG52 and paclitaxel were divided into three concentrations and co-administered in the endometrial cancer cell line Ishikawa. Figure 1 The experimental results show that NG52 can enhance the effect of paclitaxel. The inhibitory effect of combined use of NG52 and paclitaxel on tumor cells is stronger than that of single administration, and there are statistically significant differences (p<0.05). The inhibitory effect of 10μM NG52 and 10nM paclitaxel combined administration is significantly different from that of single drug (p<0.01). The results are shown in Table 2:

[0061] Table 2: Cell survival rate of endometrial cancer cell line Ishikawa treated with NG52 and paclitaxel

[0062] Drug (dosage) Cell survival rate (%) 5 μM NG52 82.80±8.99 5 nM paclitaxel 81.30±5.29 5μM NG52+5nM paclitaxel <![CDATA[58.18±1.62 a,c ]]> 10 μM NG52 47.60±2.89 10 nM paclitaxel 64.43±7.61 10μM NG52+10nM paclitaxel <![CDATA[27.22±1.15 b,c ]]> 20 μM NG52 20.60±0.99 20 nM paclitaxel 39.63±4.25 20μM NG52+20nM paclitaxel <![CDATA[25.36±1.83 c ]]>

[0063] Note: a means that compared with NG52, there is a statistically significant difference p<0.05, b means that compared with NG52, there is a very significant difference p<0.01, c means that compared with paclitaxel, there is a statistically significant difference p<0.05

[0064] Example 3: Nude mouse transplant tumor model to detect the inhibitory effect of NG52 on mouse endometrial cancer

[0065] 200 μl (about 1x10) of Ishikawa endometrial cancer cells were inoculated into the axilla of female BALB / c nude mice aged 28-35 days. 6 When the tumor volume reaches 50-100mm 3Afterwards, mice were randomly assigned to negative control group and NG52 80mg / kg medication group, with 6 nude mice in each group, and the drug was administered 5 times a week, once a day, for 3 consecutive weeks. Observe the reactions of the nude mice in all aspects, and record the changes in animal status and body weight. Use a vernier caliper to measure the long axis and short axis of the tumor twice a week, and calculate the tumor volume. 24h after the last administration, the nude mice were killed, the tumor tissues were cut out, and fixed with 10% formalin. Tumor volume was used as an indicator to evaluate the inhibitory effect of the inhibitor on the growth of endometrial cancer transplanted tumors. The experimental results showed that the tumor formation rate of Ishikawa cells was 65.2% 21 days after inoculation. In this experiment, the tumor volume reached the experimental standard 21 days after inoculation and was grouped into 2 groups, each with 6 nude mice. Compared with the negative control group, the drug administration group showed significant difference on the 11th day of administration (p=0.023, p<0.05). The best T / C ratio appeared on the 11th day of administration, T / C=0.448, and the tumor inhibition rate (TGI) was 55.2%. The experimental endpoint, that is, the 19th day of administration, still had a significant tumor inhibition trend, and the tumor inhibition rate was 42.1%. Table 3 shows the inhibitory effect of the drug administration group and the control group on mouse endometrial cancer. Figure 2 The growth curve of Ishikawa cell transplanted tumor after drug action is shown. In the experiment, the weight of nude mice in the drug administration group remained stable and increased to a certain extent after administration, while the weight of the negative control group continued to decrease, but there was no statistical difference in the weight values. The nude mouse weight numerical results are shown in Table 4, and the weight change curve of nude mice during drug administration is shown in Figure 3 .

[0066] Table 3 Experimental results of the inhibitory effect of the drug administration group and the control group on mouse endometrial cancer (n=6)

[0067]

[0068] Note: a means there is a statistically significant difference compared with the negative control group p<0.05

[0069] Table 4 Body weight changes of nude mice during drug administration (n=6)

[0070] Days after drug administration Body weight of negative control group (g) Body weight of NG52-administered group (g) Day 1 21.17±1.27 22.46±1.17 Day 4 20.17±1.09 21.80±1.52 Day 8 20.52±1.22 21.60±1.79 Day 11 20.42±1.42 21.13±1.94 Day 16 18.75±1.48 20.21±1.54 Day 19 18.59±1.87 19.68±1.54

[0071] Example 4: Inhibitory effect of NG52 on ovarian cancer Ovcar-3 cell line

[0072] Ovarian cancer Ovcar-3 cells in the logarithmic growth phase were digested with 0.25% trypsin to obtain 1×10 5 / ml, and 1×10 4Each well was inoculated in a 96-well plate, 100 μl per well, and 3 replicates were set up in each group. The cells were placed in a 5% CO2, 37°C incubator for culture. After the cells adhered to the wall, different concentrations of NG52 were added, and the final concentrations of NG52 were 31.2, 15.6, 7.8, 3.9, 1.95, 0.98, 0.49, 0.24, and 0.12 μM, respectively. After the cells were treated with drugs for 72 hours, 10 μl of CCK-8 solution was added to each well and continued to be cultured. After 2 hours, the absorbance of each well at a wavelength of 450 nm was detected with an enzyme marker to calculate the IC 50 The cell survival curve of Ovcar-3 cells after administration of NG52 is shown in Figure 4 .

[0073] The protection content of the present invention is not limited to the above embodiments. Without departing from the spirit and scope of the inventive concept, changes and substitutions that can be thought of by those skilled in the art are included in the present invention, and the protection scope is defined by the attached claims.

Claims

1. Use of PGK1 inhibitor NG52 or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating endometrial tumors.

2. The use according to claim 1, wherein the endometrial tumor is endometrial cancer.

3. The use according to claim 1 or 2, wherein the endometrial cancer is adenocarcinoma.

4. The use according to claim 1 or 2, wherein the endometrial tumor or endometrial cancer is caused by an Ishikawa cell line, a HEC-1-A cell line or a HEC-1-B cell line.

5. A composition for treating endometrial tumors, comprising PGK-1 inhibitor NG52 or a pharmaceutically acceptable salt thereof, and optionally one or more pharmaceutically acceptable carriers.

6. The composition according to claim 5, further comprising paclitaxel or a pharmaceutically acceptable salt thereof, and / or one or more active ingredients other than paclitaxel for treating endometrial tumors.

7. Use of PGK1 inhibitor NG52 or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating ovarian tumors.

8. The use according to claim 7, wherein the ovarian tumor is ovarian cancer.

9. The use according to claim 7, wherein the ovarian cancer is caused by Ovcar-3 cell line.

10. A composition for treating ovarian tumors, comprising PGK-1 inhibitor NG52 or a pharmaceutically acceptable salt thereof, and one or more active ingredients for treating ovarian tumors other than NG52 or a pharmaceutically acceptable salt thereof.

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