Application of Nedisertib in the treatment of spinal cord glioma

Abstract

The present invention provides the use of Nedisertib in the treatment of spinal cord gliomas. This application first discovered that Nedisertib can inhibit the growth of spinal cord glioma cells. Through combined radiotherapy, it was found that the combination of Nedisertib and radiotherapy can more significantly inhibit the growth of spinal cord glioma cells. These findings highlight the therapeutic value of Nedisertib in spinal cord tumors, especially its value in sensitizing to radiotherapy, and provide new ideas for the treatment of spinal cord gliomas.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine, and specifically relates to the application of Nedisertib in treating spinal cord glioma. Background Art

[0002] Intramedullary spinal cord tumors (IMSCT) are relatively rare malignant tumors of the central nervous system, accounting for approximately 4-10% of CNS tumors. Intramedullary spinal cord gliomas originate from the spinal cord ectoderm and account for approximately 80% of intramedullary spinal cord tumors. Initially, spinal cord gliomas typically present asymptomatically, and by the time they are detected, the tumors have already grown to considerable size. Spinal cord gliomas can compress the spinal cord, leading to neurological dysfunction and, in severe cases, death. Due to their unique location, surgical resection remains the preferred treatment option. However, the small size and invasive nature of spinal cord gliomas make surgery challenging. Excessive resection can impair spinal cord function, leading to serious consequences such as paralysis and incontinence. High-level cervical intramedullary surgery can cause respiratory distress or even death. Incomplete resection of the tumor tissue can result in residual tumor cells infiltrating the spinal cord parenchyma, leading to recurrence. Radiotherapy as an adjunctive treatment for spinal cord gliomas remains controversial. Some studies believe that radiotherapy can aggravate spinal cord injury and cause serious spinal cord complications, and the scars formed at the lesion site after radiotherapy will affect secondary surgery.

[0003] Therefore, finding a new drug to treat spinal cord glioma is of great importance to this field. Summary of the Invention

[0004] To overcome the deficiencies of the prior art, the present invention provides the use of Nedisertib in the treatment of spinal cord glioma.

[0005] To achieve the above objectives, the present invention adopts the following technical solutions.

[0006] The first aspect of the present invention provides the use of Nedisertib in preparing a pharmaceutical composition for treating spinal cord glioma.

[0007] Furthermore, the spinal cord glioma is a mutant spinal cord glioma.

[0008] Furthermore, the mutant spinal cord glioma is an H3 K27M mutant spinal cord glioma.

[0009] The second aspect of the present invention provides the use of Nedisertib in preparing a pharmaceutical composition for sensitizing spinal cord glioma to radiotherapy.

[0010] Furthermore, the spinal cord glioma is a mutant spinal cord glioma.

[0011] Furthermore, the mutant spinal cord glioma is an H3 K27M mutant spinal cord glioma.

[0012] Furthermore, the pharmaceutical composition also includes other drugs / other radiosensitizers for treating spinal cord glioma.

[0013] Furthermore, the other drugs for treating spinal cord glioma include methotrexate, cytarabine, palbociclib, temozolomide, and doxorubicin.

[0014] Furthermore, the other radiosensitizers include metronidazole, misonidazole, nitroimidazole, benzamide, nicotinamide, cisplatin, mitomycin, tenizamine, nitrosourea, and mercaptopurine.

[0015] Furthermore, the pharmaceutical composition also includes pharmaceutically acceptable excipients.

[0016] Furthermore, the pharmaceutically acceptable excipients include diluents, binders, surfactants, wetting agents, adsorption carriers, lubricants, fillers, and disintegrants.

[0017] Furthermore, the dosage forms of the pharmaceutical composition include solutions, tablets, powders, suspensions, emulsions, granules, capsules, pills, inhalants, gels, suppositories, creams, jellies, and sprays.

[0018] The third aspect of the present invention provides a pharmaceutical composition for treating spinal cord glioma / radiotherapy sensitization of spinal cord glioma, wherein the pharmaceutical composition comprises Nedisertib.

[0019] Furthermore, the spinal cord glioma is a mutant spinal cord glioma.

[0020] Furthermore, the mutant spinal cord glioma is an H3 K27M mutant spinal cord glioma.

[0021] The fourth aspect of the present invention provides a method for inhibiting the growth of spinal cord glioma cells in vitro, comprising administering Nedisertib.

[0022] Furthermore, the spinal cord glioma is a mutant spinal cord glioma.

[0023] Furthermore, the mutant spinal cord glioma is an H3 K27M mutant spinal cord glioma.

[0024] Furthermore, the method is a non-therapeutic method.

[0025] Advantages and beneficial effects of the present invention:

[0026] This application discovered for the first time that Nedisertib can inhibit the growth of spinal cord glioma cells. Through combined radiotherapy, it was found that Nedisertib combined with radiotherapy can more significantly inhibit the growth of spinal cord glioma cells. These findings highlight the therapeutic value of Nedisertib in spinal cord tumors, especially its value in sensitizing to radiotherapy, and provide new ideas for the treatment of spinal cord gliomas.

[0027] Biomaterial deposit information

[0028] SCA-S02:

[0029] Scientific description: human cells; depository: General Microbiology Center of China Culture Collection Administration of Microorganisms (CGMCC); deposit address: No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing; deposit date: January 22, 2024; deposit number: CGMCC NO.45809.

[0030] SCA-S09:

[0031] Scientific description: human cells; depository: General Microbiology Center of China Culture Collection Administration of Microorganisms (CGMCC); deposit address: No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing; deposit date: January 22, 2024; deposit number: CGMCC NO.45810.

[0032] SCA-S10:

[0033] Scientific description: human cells; depository: General Microbiology Center of China Culture Collection Administration of Microorganisms (CGMCC); deposit address: No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing; deposit date: January 22, 2024; deposit number: CGMCC NO.45811.

[0034] SCA-S12:

[0035] Scientific description: human cells; depository: General Microbiology Center of China Culture Collection Administration of Microorganisms (CGMCC); deposit address: No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing; deposit date: January 22, 2024; deposit number: CGMCC NO.45812.

[0036] SCA-S41:

[0037] Scientific description: human cells; depository: General Microbiology Center of China Culture Collection Administration of Microorganisms (CGMCC); deposit address: No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing; deposit date: January 22, 2024; deposit number: CGMCC NO.45813. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 This is a diagram of the gene mutations in spinal cord glioma cells;

[0039] Figure 2 This is a graph showing the sensitivity of spinal cord glioma cells to Nedisertib;

[0040] Figure 3 This is a graph measuring the sensitivity of spinal cord glioma cells to the combination of Nedisertib and radiotherapy;

[0041] Figure 4 This is a fluorescent live imaging image of spinal cord glioma cells in mice;

[0042] Figure 5 This is a graph showing the growth curve of spinal cord glioma cells in mice;

[0043] Figure 6 This is a survival curve of mice after spinal cord glioma cells were implanted into mice;

[0044] Figure 7 This is a diagram showing the inhibitory effect of anti-tumor drugs on spinal cord glioma cells SCA_S02;

[0045] Figure 8 This is a diagram showing the inhibitory effect of anti-tumor drugs on spinal cord glioma cells SCA_S09. DETAILED DESCRIPTION

[0046] The following provides definitions of some terms used in this specification. Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0047] The present invention provides the use of Nedisertib in preparing a pharmaceutical composition for treating spinal cord glioma.

[0048] In some embodiments, Nedisertib (M3814) also includes pharmaceutically acceptable salts, solvates, and cocrystals of Nedisertib.

[0049] In some embodiments, pharmaceutically acceptable salts are preferably derived from inorganic or organic acids and bases. Examples of such acid salts include, but are not limited to, acetate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, lucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, lactate, maleate, methanesulfonate, 2-naphthalenesulfonic acid Salts, such as nicotinates, oxalates, pamoates, pectinates, persulfates, 3-phenyl-propionates, picrates, pivalates, propionates, succinates, tartrates, thiocyanates, toluenesulfonates, undecanoates, hydrohalides (e.g., hydrochlorides and hydrobromides), sulfates, phosphates, nitrates, sulfamates, malonates, salicylates, methylene-bis-b-hydroxynaphthoate, gentisates, isethionates, di-p-toluoyl tartrates, ethanesulfonates, cyclohexylsulfamates, quinates, and the like. Pharmaceutically acceptable base addition salts include, but are not limited to, those derived from alkali metal or alkaline earth metal bases or conventional organic bases, such as triethylamine, pyridine, piperidine, morpholine, N-methylmorpholine, ammonium salts, alkali metal salts (such as sodium and potassium salts), alkaline earth metal salts (such as calcium and magnesium salts), salts with organic bases (such as dicyclohexylamine salts, N-methyl-D-glucamine), and salts with amino acids such as arginine, lysine.

[0050] In some embodiments, a solvate refers to an association or complex of one or more solvent molecules with a compound of Nedisertib. Examples of solvents that form solvates include, but are not limited to, water, isopropanol, ethanol, methanol, dimethyl sulfoxide (DMSO), ethyl acetate, acetic acid, acetonitrile, and ethanolamine. A hydrate refers to a complex in which the solvent molecule is water.

[0051] In some embodiments, a co-crystal refers to a crystal structure containing at least two different compounds that are solids in pure form under ambient conditions. A co-crystal is formed from neutral molecular species, and all species remain neutral after crystallization. Preferably, a co-crystal is a crystalline homogeneous material in which two or more building blocks are present in a defined stoichiometric ratio.

[0052] The pharmaceutical composition further includes pharmaceutically acceptable excipients.

[0053] In some embodiments, a pharmaceutically acceptable excipient is used to refer to a material that is compatible with a recipient, preferably a mammal, more preferably a human, and suitable for delivering the active agent to the target site without disrupting the activity of the agent. The toxicity or side effects associated with the pharmaceutically acceptable excipient (if any) are preferably commensurate with a reasonable risk / benefit ratio for the intended use of the active agent.

[0054] In some embodiments, pharmaceutically acceptable excipients include, but are not limited to, diluents, binders, surfactants, humectants, adsorbent carriers, lubricants, fillers, and disintegrants. These pharmaceutically acceptable excipients are used, as needed, to help stabilize the formulation, enhance its activity or bioavailability, or produce an acceptable taste or odor when orally administered. The formulations that can be used in such pharmaceutical compositions can be in the form of the original compound itself or, optionally, in the form of a pharmaceutically acceptable salt. The pharmaceutical composition thus formulated can be administered by any appropriate method known to those skilled in the art, as needed.

[0055] Among them, diluents include but are not limited to lactose, sodium chloride, glucose, urea, starch, and water.

[0056] Binders include, but are not limited to, starch, pregelatinized starch, dextrin, maltodextrin, sucrose, gum arabic, gelatin, methylcellulose, carboxymethylcellulose, ethylcellulose, polyvinyl alcohol, polyethylene glycol, polyvinylpyrrolidone, alginic acid and alginates, xanthan gum, hydroxypropyl cellulose, and hydroxypropyl methylcellulose.

[0057] Surfactants include, but are not limited to, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, stearic acid monoglyceride, and cetyl alcohol.

[0058] Humectants include, but are not limited to, glycerin.

[0059] Adsorptive supports include, but are not limited to, bentonite, silica gel, kaolin, and bentonite.

[0060] Lubricants include, but are not limited to, zinc stearate, glyceryl monostearate, polyethylene glycol, talc, calcium and magnesium stearate, polyethylene glycol, boric acid powder, hydrogenated vegetable oil, sodium stearyl fumarate, polyoxyethylene monostearate, monolauric sucrose ester, sodium lauryl sulfate, magnesium lauryl sulfate, and magnesium lauryl sulfate.

[0061] Fillers include, but are not limited to, mannitol (granular or powdered), xylitol, sorbitol, maltose, erythrose, microcrystalline cellulose, polymeric sugars, coupling sugars, glucose, lactose, sucrose, dextrin, starch, sodium alginate, laminarin powder, agar powder, calcium carbonate, and sodium bicarbonate.

[0062] Disintegrants include, but are not limited to, cross-linked vinyl pyrrolidone, sodium carboxymethyl starch, low-substituted hydroxypropyl methyl, cross-linked sodium carboxymethyl cellulose, and soybean polysaccharides.

[0063] In some embodiments, the pharmaceutical compositions described above may be administered to a subject by any convenient route of administration (whether systemically / peripherally or at the site of desired action), including, but not limited to, one or more of the following: oral (e.g., as a tablet, capsule, or as an ingestible solution), topical (e.g., transdermal, intranasal, ocular, buccal, and sublingual), parenteral (e.g., using injection or infusion techniques, and including, for example, by injection (e.g., subcutaneous, intradermal, intramuscular, intravenous, intraarterial, intracardiac, intrathecal, intraspinal, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subcutaneous, intraarticular, subarachnoid, or intrasternal), for example, implantation of a depot (e.g., subcutaneously or intramuscularly), pulmonary (e.g., by inhalation or insufflation therapy, through the mouth or nose using, for example, an aerosol), gastrointestinal.

[0064] In some embodiments, the pharmaceutical composition can be manufactured by methods well known in the art, such as conventional granulation, mixing, dissolution, encapsulation, lyophilization or emulsification, etc. The pharmaceutical composition can be prepared in various forms, including but not limited to solutions, tablets, powders, suspensions, emulsions, granules, capsules, pills, inhalants, gels, suppositories, creams, jellies, and sprays.

[0065] In some embodiments, pharmaceutical composition will change according to required effect.Therefore, the optimal content of the pharmaceutical composition of the present application can be easily determined by those skilled in the art, and can be adjusted according to including following various factors: the type and severity of the disease, the content of other components contained in the pharmaceutical composition, the type of preparation, the patient's age, body weight, general health, sex and diet, application time, administration route, the secretion rate of the drug, the duration of treatment and the medicine used simultaneously.The amount of the pharmaceutical composition should consider the factors to determine, and it can be applied once a day or in several portions. However, it should be understood that the actual dose of the active ingredient should consider various relevant factors to determine, and it includes the disease treated, the severity of the disease, the route of application and the patient's weight, age and sex.Therefore, dosage does not limit the scope of the application in any way.

[0066] In some embodiments, treatment refers to clinical intervention that attempts to alter the natural course of the disease in the individual being treated, and can be performed for prevention or during clinical pathology. Desirable therapeutic effects include, but are not limited to, preventing the occurrence or recurrence of the disease, alleviating symptoms, reducing any direct or indirect pathological consequences of the disease, preventing metastasis, reducing the rate of disease progression, improving or relieving the disease state, and alleviating or improving prognosis.

[0067] The present invention will be further described below with reference to specific examples. It should be understood that the specific embodiments described herein are presented by way of example and are not intended to limit the present invention. The main features of the present invention may be applied to various embodiments without departing from the scope of the present invention.

[0068] Example 1

[0069] The process of suspension culture of spinal cord glioma cells: Place the brain glioma tissue block (brain glioma tissue surgically removed at Tiantan Hospital in accordance with medical ethics) in a beaker, rinse it three times with Hanks solution to remove blood stains; then place it in a mixture containing penicillin and streptomycin for 60 minutes; use ophthalmic scissors to cut the tissue into 2-3 mm pieces for easy digestion; add trypsin solution equivalent to 50 times the volume of the total amount of tissue block, and then pour it into a conical flask, tie the bottle mouth or plug it with a rubber stopper; place it in a 37°C incubator for digestion, and shake it every 20 minutes during the digestion process; the digestion time is 60 minutes; then filter out the tissue blocks that have not been fully digested through a suitable stainless steel sieve; centrifuge the digestion solution at 800 rpm to obtain sample cells, aspirate the supernatant, and add primary culture medium to the precipitate to a cell density of 10 5 / mL, and then cultured in a constant temperature incubator at 37°C. The base medium of the primary culture medium is a suspension medium, which includes: 20ng / mL EGF cytokine, 20ng / mL bFGF cytokine, 20ng / mL streptomycin and 20ng / mL penicillin, B27 (50×) and 20ng / mL transferrin.

[0070] The single cell suspension obtained by the above suspension culture was inoculated into an ultra-low adsorption culture dish for culture, and then digested into single cells with digestive enzymes. When the operation was repeated and subcultured to the fourth generation, some primary cells died, stopped growing, or grew slowly, while other primary cells were able to show a good proliferation state in a serum-free suspension culture medium. These cell lines showing a good proliferation state were selected as further screening objects, and MTT experiments and Transwell experiments were performed to detect the proliferation and migration abilities of the cell lines. The cell lines finally obtained included SCA-S10, SCA-S12, SCA-S41, SCA-S09, and SCA-S02. The gene mutations and copy number variations of the spinal cord glioma cells were detected by whole exome sequencing. The results are as follows Figure 1 As shown, it can be seen that different spinal cord glioma cells all have H3 K27M mutation (H3F3AK27M).

[0071] In this example, the spinal cord H3 K27M mutant cells derived from the above patients were divided into two groups: "high proliferation and replication stress type" and "high immune infiltration type". Among them, SCA-S10 and SCA-S12 are "high immune infiltration type" tumor patient-derived cell models, and SCA-S41, SCA-S09, and SCA-S02 are "high proliferation and replication stress type" cell models.

[0072] The sensitivity of the nedisertib (M3814) compound to the drug was evaluated using the aforementioned cell model. The specific procedure was as follows: Glioblastoma cells in the logarithmic growth phase were trypsinized and centrifuged to obtain a cell pellet. The pellets were resuspended in complete culture medium and counted. Based on the counts, 5,000 cells were seeded per well in a 96-well cell culture plate and incubated in a 37°C incubator with 5% CO2. After 24 hours, the cells were treated with the drug. Nedisertib (M3814) compound was dissolved in DMSO to prepare a stock solution, which was then diluted in complete culture medium to various drug concentrations: 0, 0.04, 0.2, and 1.5 μM. The medium was removed from the wells, and 100 μL of the corresponding drug solution was added to each well. The plates were returned to the incubator, and cell proliferation was measured after 6 days. During the test, the CCK8 working solution was prepared in advance. The appropriate volume of working solution was prepared according to 100 μL serum-free culture medium and 10 μL CCK8 per well. The solution was placed in the dark. The plate was removed from the incubator, the cell culture medium in the wells to be tested was removed, and 110 μL CCK8 working solution was added to each well. After incubation for 2 hours, the absorbance at 450 nm was measured on a microplate reader. The inhibition rate corresponding to each concentration was calculated. The IC50 value at the corresponding time point was calculated using GraphPad 7.0 software. The results are shown as follows: Figure 2 As shown, the "high immune infiltration type" SCA-S10 and SCA-S12 cells are more resistant to the treatment of Nedisertib (M3814) compound, and the "high proliferation and replication stress type" cells "SCA-S41, SCA-S09, SCA-S02" are relatively sensitive to the treatment of Nedisertib (M3814) compound.

[0073] Radiotherapy is currently the standard treatment for H3 K27 mutant spinal cord gliomas. This example further evaluated whether the Nedisertib (M3814) compound combined with radiotherapy can effectively sensitize the effect of radiotherapy. The specific evaluation process includes: treating the above-mentioned spinal cord glioma cells SCA-S41, SCA-S09, SCA-S02, SCA-S10 and SCA-S12 with radiotherapy doses of 0, 2, 4, 6, and 8 Gy, respectively, and simultaneously administering 0, 0.04, 0.2, and 1.5 μmol of the Nedisertib (M3814) compound, respectively. After 6 days of radiotherapy, the number of surviving cells in different groups was measured to evaluate their sensitivity to radiotherapy. The results are shown in FIG. Figure 3 As shown, it can be seen intuitively that for high proliferation and replication stress type H3 K27 mutant spinal cord glioma cells, increasing the concentration of Nedisertib (M3814) compound can significantly sensitize the effect of radiotherapy.

[0074] Example 2

[0075] In this example, an orthotopic xenograft model was established by injecting luciferase-expressing spinal cord H3 K27M mutant tumor cells, SCA09, into the spinal cord of nude mice. The therapeutic effects of Nedisertib (M3814) alone and in combination with radiotherapy were measured. The specific measurement process is as follows:

[0076] SCA09 cells were injected into the spinal cord of nude mice and the cells were allowed to grow in the spinal cord glioma for 14 days, which was set as day 0. The control group was given normal saline by gavage on days 0, 1, 2, 7, 8, 9, 14, 15 and 16, and simulated radiotherapy was given 4 hours after the administration. The Nedisertib (M3814) group was given Nedisertib (M3814) by gavage on days 0, 1, 2, 7, 8, 9, 14, 15 and 16, and simulated radiotherapy was given 4 hours after the administration. Radiotherapy; Radiation group: administered with normal saline by gavage on days 0, 1, 2, 7, 8, 9, 14, 15, and 16, and 1 Gy of radiotherapy was given 4 hours after administration; Nedisertib (M3814) + radiation group: administered with Nedisertib (M3814) by gavage on days 0, 1, 2, 7, 8, 9, 14, 15, and 16, and 1 Gy of simulated radiotherapy was given 4 hours after administration; Fluorescent in vivo imaging was used to show the size of cells in mice, and the results are as follows Figure 4As shown in the results, compared with the control group, both the Nedisertib (M3814) group and the radiotherapy group alone could effectively reduce the tumor volume on day 28, while the Nedisertib (M3814) + radiotherapy group could more significantly reduce the tumor volume on day 28.

[0077] This example further measured the tumor growth curve, such as Figure 5 As shown in the figure, it can be seen from the tumor growth curve (change in average bioluminescence intensity) that the use of Nedisertib (M3814) or radiotherapy alone can inhibit the growth rate of tumors to a certain extent, while the use of Nedisertib (M3814) and radiotherapy together can more significantly inhibit the growth rate of mouse tumors.

[0078] In addition, compared with the control group, Nedisertib (M3814) or radiotherapy can prolong the survival of tumor-bearing mice to a certain extent, but the combination of Nedisertib (M3814) and radiotherapy can further prolong the survival of mice ( Figure 6 ).

[0079] These findings highlight the therapeutic value of Nedisertib (M3814) in spinal cord tumors, especially its value in sensitizing to radiotherapy.

[0080] Comparative Example

[0081] This comparative example further measured the inhibitory effects of Nedisertib (M3814) and other commonly used compounds on the H3 K27M subtype of spinal cord glioma according to the determination method of Example 1. The drug concentrations and effects are shown in Table 1. Figure 7-8 , IC50 values ​​(μM) are shown in Table 1.

[0082] Table 1 Inhibitory effect of drugs on spinal cord glioma

[0083]

[0084] It can be seen that compared with other anti-tumor drugs, the Nedisertib (M3814) compound provided in this application can effectively inhibit the growth of H3 K27M mutant spinal cord glioma and can further sensitize radiotherapy, providing a new solution for the treatment of H3 K27M subtype spinal cord glioma.

[0085] The above embodiments are only provided for understanding the method and core concept of the present invention. It should be noted that, without departing from the principles of the present invention, a number of improvements and modifications may be made to the present invention by a person skilled in the art, and such improvements and modifications shall fall within the scope of protection of the claims of the present invention.

Claims

1. Use of Nedisertib in the preparation of a pharmaceutical composition for treating spinal cord glioma; The spinal cord glioma is an H3 K27M mutant spinal cord glioma.

2. The use of Nedisertib in the preparation of a pharmaceutical composition for sensitizing spinal cord glioma to radiotherapy; The spinal cord glioma is an H3 K27M mutant spinal cord glioma.

3. The use according to claim 1 or 2, characterized in that The pharmaceutical composition also includes other drugs / other radiosensitizers for treating spinal cord glioma.

4. The use according to claim 3, characterized in that The other drugs for treating spinal cord glioma include methotrexate, cytarabine, palbociclib, temozolomide, and doxorubicin.

5. The use according to claim 3, characterized in that The other radiosensitizers include metronidazole, misonidazole, nitroimidazole, benzamide, nicotinamide, cisplatin, mitomycin, tenizamine, nitrosourea, and mercaptopurine.

6. The use according to claim 1 or 2, characterized in that The pharmaceutical composition further includes pharmaceutically acceptable excipients.

7. The use according to claim 6, characterized in that The pharmaceutically acceptable excipients include diluents, binders, surfactants, wetting agents, adsorption carriers, lubricants, fillers, and disintegrants.

8. The use according to claim 1 or 2, characterized in that The dosage forms of the pharmaceutical composition include solutions, tablets, powders, suspensions, emulsions, granules, capsules, pills, inhalants, gels, suppositories, creams, and jellies.

9. A method for inhibiting the growth of spinal cord glioma cells in vitro for non-therapeutic purposes, characterized in that: The method comprises administering Nedisertib; The spinal cord glioma is an H3 K27M mutant spinal cord glioma.

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