WO2014065537A1 - Pharmaceutical composition for preventing and treating prostate cancer - Google Patents

Abstract

The present invention provides a pharmaceutical composition for preventing and treating prostate cancer. The pharmaceutical composition for preventing and treating prostate cancer of the present invention comprises JFD00244, tetrindole mesylate, 5-nonyloxytryptamine oxalate or clofazimine as an active ingredient. The pharmaceutical composition for preventing and treating prostate cancer of the present invention shows anticancer effects of selectively killing prostate cancer cells by inhibiting the activity of BMX, and inhibiting the proliferation of prostate cancer cell lines. Therefore, the pharmaceutical composition for preventing and treating prostate cancer of the presentinvention can overcome problems and limitations of conventional hormone therapy and radiation therapy for prostate cancer and can be applied as a targeted anticancer drug for prostate cancer.

Description

Pharmaceutical composition for preventing and treating prostate cancer

The present invention relates to a pharmaceutical composition for preventing and treating prostate cancer, and more particularly, to finding a compound having a novel indication in the field of preventing and treating prostate cancer and providing it as a pharmaceutical composition for preventing and treating new prostate cancer. .

Specifically, the present invention relates to the discovery of a compound having a prostate cancer prevention and treatment efficacy and to provide it as a pharmaceutical composition for preventing and treating prostate cancer containing the same as an active ingredient.

Prostate cancer is a common tumor in western men, with prostate cancer occurring in the West at 30% in men over 50 and 80% in men over 80, and is one of the major causes of male death. Recently, the incidence of prostate cancer is increasing in Korea due to westernization and aging of the diet.

In general, treatment for prostate cancer occurs by surgically removing the prostate gland to remove the cancer, removing prostate cancer, hormonal therapy that inhibits the production or action of male hormones, chemotherapy using anticancer agents, and cancer cells using radiation. There is a radiation therapy that necrosis. In early prostate cancer, extraction or radiotherapy may be performed. Unlike other cancers, prostate cancer does not show rapid cell division, so chemotherapy is not effective and hormone therapy is known to be effective.

Although prostatectomy has a high clinical effect, there are complications such as incontinence, impotence, and urethral stenosis, and hormonal therapy cannot be used for hormone-independent prostate cancer or hormone-resistant prostate cancer. In addition, radiation therapy has a problem that radiation is irradiated to the bladder and rectum around the prostate, accompanied by complications such as rectal bleeding, impotence.

To date, prostate cancer is known to be associated with tyrosine kinase. Tyrosine kinase, which is responsible for signal transduction of cells, is involved in the transformation of prostate epithelial cells and tumor progression.

In this regard, BMX (BMX non-receptor tyrosine kinase) is reported to be involved in cancer growth and metastasis through PI3K / AKT, a typical signaling pathway involved in the cancer metastasis process when stimulated with EGF (epithelial growth factor). (YUN QIU et al., Cell Biol. January 28 (1998), 3644-3649). In addition, BMX has been shown to mediate subsequent signaling pathways after activation through the Tumor Necrosis Factor (TNF) and its receptors in angiogenesis, an important step in cancer metastasis (Shi Pan et al. , Cell Biol. August 8 (2002), 7512-7523).

As a result, the present inventors noted that BMX is involved in cancer growth and metastasis as described above, and after diligently researching anticancer candidates targeting BMX, the present inventors selectively selected prostate cancer cells through inhibition of BMX activity. The discovery and discovery of substances that can kill and inhibit cell proliferation have led to the identification of compounds with novel indications in the field of prostate cancer prevention and treatment.

An object of the present invention relates to a pharmaceutical composition for preventing and treating prostate cancer, and more particularly, to find a compound having a novel indication in the field of preventing and treating prostate cancer and to provide it as a pharmaceutical composition for preventing and treating new prostate cancer. .

Specifically, it is an object of the present invention to find a compound having the effect of preventing and treating prostate cancer and to provide a pharmaceutical composition for preventing and treating prostate cancer containing the same as an active ingredient.

In order to solve the problems of the prior art as described above and to achieve the object of the present invention, the present invention provides a pharmaceutical composition for preventing and treating prostate cancer.

The pharmaceutical composition for preventing and treating prostate cancer of the present invention includes JFD00244, Tetrindole mesylate, 5-nonyloxytryptamine oxalate, or clofazimine as an active ingredient. do. JFD00244 is a compound having Formula 1 below, tetralindol mesylate below Formula 2, 5-nonyloxytrytamine oxalate below Formula 3 and clofazimin below Formula 4.

Formula 1

Formula 2

Formula 3

Formula 4

The pharmaceutical composition for preventing and treating prostate cancer in one embodiment of the present invention is characterized by inhibiting the activity of BMX (BMX non-receptor tyrosine kinase).

Preferably, the pharmaceutical composition for preventing and treating prostate cancer of the present invention includes clofazimin as an active ingredient.

The pharmaceutical composition for preventing and treating prostate cancer of the present invention as described above may be formulated in various oral or parenteral dosage forms. Formulations for oral administration include, for example, tablets, pills, hard and soft capsules, solutions, suspensions, emulsifiers, syrups, granules, elixirs, etc. These formulations may contain diluents (e.g., lactose) in addition to the active ingredients. , Dextrose, sucrose, mannitol, sorbitol, cellulose and / or glycine), lubricants such as silica, talc, stearic acid and its magnesium or calcium salts and / or polyethylene glycols. Tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidine, optionally starch, agar, alginic acid or its Disintegrants or boiling mixtures such as sodium salts and / or absorbents, colorants, flavors, and sweeteners.

The pharmaceutical composition for preventing and treating prostate cancer of the present invention as described above may be administered parenterally, and the parenteral administration is, for example, by subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection. All. In this case, to formulate into a parenteral formulation, a compound of Formula 1 to Formula 4 or a pharmaceutically acceptable salt thereof is mixed with water with a stabilizer or buffer to prepare a solution or suspension, which is administered in unit doses of ampoules or vials. It can be manufactured in a mold.

In addition, the pharmaceutical compositions for preventing and treating prostate cancer of the present invention as described above are sterile and / or adjuvant such as preservatives, stabilizers, hydrates or emulsifiers, salts and / or buffers for the control of osmotic pressure, and other therapeutically Useful materials may be contained and formulated according to conventional methods of mixing, granulating or coating.

On the other hand, in the pharmaceutical composition for preventing and treating prostate cancer of the present invention as described above, "administration" means introducing a predetermined substance into the patient by any suitable method, the route of administration of the compound of Formula 1 to Formula 4 The drug can be administered via any general route so long as it can reach the target tissue. For example, it may include, but is not limited to, intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, topical administration, intranasal administration, pulmonary administration, rectal administration, and the like. In addition, the pharmaceutical composition for preventing and treating prostate cancer of the present invention may be administered by any device that can move the active ingredient of Formula 1 to the target cell.

In addition, the therapeutically effective amount of the compound of Formula 1 to Formula 4 contained in the pharmaceutical composition for preventing and treating prostate cancer of the present invention means an amount required for administration in order to expect a therapeutic effect of the disease. Therefore, the disease type of the patient, the severity of the disease, the type of active ingredients (compounds of Formula 1 to Formula 4) administered, the type of formulation, the age, sex, weight, health status, diet, administration time and administration of the drug It can be adjusted according to the method. For example, when an adult compound of Formula 1 to Formula 4 is administered as an active ingredient, it may be administered at a dose of 0.001 mg / kg to 500 mg / kg once daily.

The pharmaceutical composition for preventing and treating prostate cancer of the present invention can selectively kill prostate cancer cells through inhibition of BMX activity and exhibit an anticancer effect of inhibiting proliferation of prostate cancer cell lines.

Therefore, the pharmaceutical composition for preventing and treating prostate cancer of the present invention overcomes the problems and therapeutic limitations of conventional hormone therapy and radiation therapy for prostate cancer and has the advantage of being applicable as a target anticancer agent for prostate cancer.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a diagram schematically illustrating an outline of a method for screening a primary screen of a compound that inhibits BMX activity as a target protein from an anticancer candidate compound library.

FIG. 2 shows anticancer candidate compounds (Lopac P08-F02, Lopac P11-E08, Enzo P07-B03, Tocris P03-F11, Tocris P04-H11 identified through screening procedures according to Examples 1-1 and 1-2) , Tocris P10-A02, Micro 100119-06-D04, Micro 100119-10-C03, Micro 100119-13-D02, and Lopac P16-E02) have a magnetic field that interferes with the binding of the target protein BMX with Dasatinib-MNP. Confocal micrographs showing the disappearance of the unique fluorescence pattern seen upon application.

FIG. 3 shows that the four single candidate compounds finally screened according to Examples 1-3 bind with the BMX protein to interfere with the binding of the target protein BMX with Dasatinib-MNP, thereby eliminating the unique fluorescence pattern upon application of the magnetic field. Are confocal micrographs showing In FIG. 3, Lopac P08-F02 represents JFD00244, Tocris P03-F11 represents tetralindol mesylate, Tocris P04-H11 represents 5-nonyloxytrytamine oxalate, and Micro 100119-13-D02 represents clofazimine.

4 to 10 are graphs showing the results of the WST-1 assay, a cytotoxicity test performed on prostate cancer cell line 22Rv1 using the anticancer candidate compound of the present invention.

11 to 17 are graphs showing WST-1 assay results, which are cytotoxicity experiments performed on prostate cancer cell line DU145 using anticancer candidate compounds of the present invention.

18 is a graph showing the results of cell proliferation inhibition experiments performed on prostate cancer cell line 22Rv1 using the anticancer candidate compound of the present invention.

19 is a graph showing the results of cell proliferation inhibition experiments performed on prostate cancer cell line DU145 using the anticancer candidate compound of the present invention.

Figure 20 is an electrophoresis picture showing the results of BMX activity inhibition experiment performed on prostate cancer cell line 22Rv1 using the anticancer candidate compound of the present invention.

Hereinafter, the present invention will be described in more detail based on examples. The following examples of the present invention are not intended to limit or limit the scope of the present invention only to embody the present invention. From the detailed description and examples of the present invention, those skilled in the art to which the present invention pertains can easily be interpreted as belonging to the scope of the present invention. References cited in the present invention are incorporated herein by reference.

Example

Example 1 Screening of Anticancer Candidate Compounds with BMX Activity Inhibitory Efficacy

Example 1-1 Anticancer Candidate Compound Primary Screen

First, BMX activity according to the experimental method described in Korean Patent Publication No. 10-2010-0052355 (published May 19, 2010) and Korean Patent Registration No. 10-1028875 (published April 4, 2011) The compounds that inhibited were screened first.

C3-EGFP-Bmx and N1-Bmx-EGFP constructs, which are expression panels that can express genes from the target protein BMX (BMX UniProt protein knowledge database; BMX Ensembl genome database) in a fused form with fluorescent protein (FP) It was constructed according to the method described in the Republic of Korea Patent Publication No. 10-2010-0052355 and Republic of Korea Patent No. 10-1028875.

As the anticancer candidate compound library screened for the target protein BMX, a compound library known and available in the art to which the present invention pertains was used, for example, Tocriscreen Mini Set (Tocris Bioscience), LOPAC^1280TMSmall Scale (International Version) (Sigma-aldrich), by MicroSource US Collection and International Drug Collection, FDA approved drug library from Enzo, and the like.

And since the number of anticancer candidate compounds constituting the compound library of the four companies is large, as shown in (a) of Figure 1, a mixture of three to four candidate compounds are optionally bundled in a ratio of 1 to 1 each A total of 18 96-well plates received were prepared. Then, HeLa cells were inoculated in the glass bottom portion of the 96-well plate according to a method known in the art, and then the C3-EGFP-Bmx construct having the fluorescent protein gene tag attached to the Bmx gene was transferred into HeLa cells. Introduced via transfection.

The C3-EGFP-Bmx construct gene introduced into HeLa cells was expressed to express BMX protein labeled with EGFP, a green fluorescent protein, in HeLa cells. And, according to the experimental method described in the Republic of Korea Patent Publication No. 10-2010-0052355 and Republic of Korea Patent No. 10-1028875 as described above, MNP to which dasatinib, which is a compound that binds to the BMX protein is bound (Magnetic Nano Particle) introduced into HeLa cells and treated with DaLatinib and anticancer candidate compounds against BMX protein by treating HeLa cells with a concentration of 1 μM to 3 μM anticancer candidate compounds targeted for BMX activity inhibition screening Let.

When Dasatinib and the anticancer candidate compound do not compete with each other, when the magnetic field is applied in the horizontal direction of the well-plate, the fluorescent protein-labeled BMX protein and Dasatinib bound to MNP (Magnetic Nano Particle) MNP (Magnetic Nano Particle) forms a magnetization pattern along the direction of the magnetic field applied in the horizontal direction, and at the same time, the fluorescent pattern of EGFP also overlaps with the magnetization pattern according to the binding of MNP-Dasatinib-BMX protein. Will appear. On the other hand, when dasatinib and the anticancer candidate compound compete with each other, the anticancer candidate compound binds to the MBX protein, thereby forming a magnetic nanoparticle (MNP) formed along the direction of the magnetic field applied in the horizontal direction of the well-plate. The fluorescent pattern overlapping with the magnetization pattern disappears.

Therefore, the fluorescent pattern formed along the direction of the applied magnetic field in the horizontal direction of the well-plate when only Dasatinib-MNP was treated, and the fluorescent pattern when the mixture of candidate compounds were treated with Dasatinib-MNP In comparison, the mixture of candidate compounds that causes the fluorescence pattern by the magnetic field application to disappear may be first screened with the mixture of candidate compounds that bind the MBX protein (see FIG. 1A). As a result, a total of 16 well-plates were identified, which interrupted the binding of the target protein BMX and dasatinib-MNP, and disappeared when the magnetic field was applied. Candidate compounds could be screened out.

Example 1-2 Anticancer Candidate Compound Secondary Screen

As described above, 38 anticancer candidate compounds were screened through Example 1-1, followed by a mixture of candidate compounds that bind MBX protein (16 fluorescence patterns disappeared), as shown in FIG. The experiments described above were repeated for each compound constituting the well-plate) to finally discover 10 single compounds as BMX activity inhibition candidate compounds, that is, anticancer candidate compounds (see FIG. 2).

Example 1-3 Anticancer Candidate Compound Final Screen

In order to further verify the results of Example 1-1 and Example 1-2, another structure, N1-Bmx-EGFP construct, was introduced into HeLa cells, and the experimental procedures of Example 1-1 and Example 1-2 were performed. Was performed. This is considered to affect the structure or degree of activity of the BMX protein depending on the position of EGFP, which is a labeling protein that fluoresces at the C- or N-terminus of the target protein. This final validation experiment finally identified four single candidate compounds that were not affected by the tag position of the EGFP (see Table 1 and FIG. 3).

Table 1 Final screened anticancer candidate compound

Anticancer candidate compound 1	Anticancer Candidate Compound 2	Anticancer Candidate Compound 3	Anticancer Candidate Compound 4
Lopac P08-F02 (JFD00244)	Tocris P03-F11 (tetrindol mesylate)	Tocris P04-H11 (5-nonyloxytrytamine oxalate)	Micro 100119-13-D02 (clofazimine)

Example 2: In vitro Cytotoxicity Experiments on Prostate Cancer Cell Lines

Cytotoxicity experiments were carried out on DU145 (produced from the Korean Cell Line Bank) and 22Rv1 (obtained from ATCC), which are known to express BMX proteins using the four anticancer candidate compounds finally identified in Examples 1-3. Was performed. The cytotoxicity test is a method of determining an appropriate concentration (IC ₅₀ ) of an inhibitor that exhibits a biological and biochemical function that is not toxic enough to induce cell death because the degree of toxicity is different for each anticancer candidate compound. It is essential to the process.

WST-1 assay was selected for this cytotoxicity experiment, and the prostate cancer cell line (DU145: 1 × 10 ⁴ cells / well, 22Rv1: 2 ×) in three 96-well plates (SPL flat bottom; cat # 30096) 10 ⁴ cells / well) were incubated for one day after inoculation.

When the cell confluency reaches 50%, the cell starvation is performed by starving cells in a CO ₂ incubator for 24 hours by switching from full medium to serum free media. I did it. Thereafter, control compounds (eg, cathodex, dasatinib, lapatinib) and anticancer candidate compounds were added to each 96-well plate according to the concentration, and then incubated for 48 hours in a CO ₂ incubator.

10 μl of premix WST-1 (TaKaRa cat # MK 400) is added to the cultured 96-well plate and incubated in the incubator for 30 minutes to 1 hour to turn yellow. This was shown graphically by reading the absorbance at 450 nm using an ELISA reader (Promega Glomax Multi) (see FIGS. 4-10 and 11-17). Meanwhile, in FIGS. 4-10 and 11-17, the appropriate concentrations determined in the WST-1 assay for the control group and the anticancer candidate compounds are underlined.

In this example, experiments were carried out using Casodex, which is known as an inhibitor of EGF, as a control, and several papers have already used 30 μM as an IC ₅₀ value of Casodex for prostate cancer. Lapatinib and Dasatinib, known as other anticancer agents, have high cytotoxicity at low concentrations, while lapatinib has low cytotoxicity at high concentrations. This phenomenon is common in both prostate cancer cell lines expressing the target protein BMX. Therefore, the cytotoxicity was confirmed by the same method for the four anticancer candidate compounds selected in Examples 1-3 based on this.

As a result, as shown in Figures 4 to 10 and 11 to 17, the three anti-cancer substances (casodex, Dasatinib, Lapatinib) corresponding to the control group did not differ significantly in concentration, Example 1 The four candidate compounds selected at -3 were slightly different in sensitivity depending on the cell line. The appropriate concentrations of the control and anticancer candidate compounds determined through the WST-1 assay, which is a cytotoxicity test for the two prostate cancer cell lines, are shown in Table 2 below.

TABLE 2 Appropriate concentrations of control and anticancer candidate compounds identified in cytotoxicity experiments

	Cathodex	Dasatinib	Lapatinib	JFD00244	Tetridol Mesylate	5-nonyloxytrytamine oxalate	Clofazimin
22Rv1
	30 μM	100 nM	5 μM	200 nM	5 μM	500 nM	100 nM
DU145
	30 μM	100 nM	1 μM	1 μM	1 μM	500 nM	100 nM

Example 3: In vitro cell proliferation inhibition experiment on prostate cancer cell line

For cell proliferation inhibition experiments, 22Rv1 cell lines were seeded in 96-well plates at 2 × 10 ⁴ cells / well and then incubated for one day.

When the cell confluency reaches 50%, the cell starvation is performed by starving cells in a CO ₂ incubator for 24 hours by switching from full medium to serum free media. I did it. Each 96-well plate was then grown on EGF (20 ng / ml) (only for series 2 in FIG. 18), control compounds (e.g., cathodex, dasatinib, lapatinib) and anticancer candidate compounds Was added according to the concentration determined in Example 2, and then incubated for 48 hours in a CO ₂ incubator.

10 μl of premix WST-1 (TaKaRa cat # MK 400) is added to the cultured 96-well plate and incubated in the incubator for 30 minutes to 1 hour to turn yellow. The absorbance was read at 450 nm using an ELISA reader (Promega Glomax Multi). In addition, the absorbance value obtained by treating only DMSO to the same cell was set to 1, and the relative absorbances of the control and candidate compounds were converted into graphs (refer to FIG. 18).

As a result, as shown in FIG. 18, cell proliferation of 22Rv1 cells was found to be inhibited by all four anticancer candidate compounds of the present invention including dasatinib. On the other hand, despite the use of EGFR, the receptor protein of EGFR as a target protein, cathodex increased cell proliferation when treated with EGF, and this phenomenon was the same in the case of lapatinib. Of the four anticancer candidate compounds of the present invention, the remaining three anticancer candidate compounds except JFD00244 were found to inhibit cell proliferation independently of EGF, which is the anticancer candidate compound of the present invention, tetralindol mesylate, 5- Nonyloxytryptamine oxalate and clofazimine may inhibit the activity of BMX as a target protein, and this means that BMX may have an intracellular signal transduction process separate from EGF.

In addition, as shown in FIG. 19, the known prostate cancer therapeutic agent Caddex, which is related to DU145 cell proliferation, exhibited a cell proliferation inhibitory effect, and all four anticancer candidate compounds of the present invention including dasatinib and lapatinib were all present. Similar trends were shown to inhibit DU145 cell proliferation. In particular, it was confirmed that tetridol mesylate, an anticancer candidate compound of the present invention, strongly inhibited cell proliferation as much as dasatinib.

As described above, it was confirmed that all four anticancer candidate compounds of the present invention had an inhibitory effect on prostate cancer cell proliferation.

Example 4: BMX activity inhibition experiment (immunoprecipitation experiment)

For immunoprecipitation experiments, 22Rv1 cells were seeded in 9 100 mm dishes at a concentration of 1 × 10 ⁶ cells / plate, and then cultured in a cell incubator for 24 hours. After removing all of the medium, all remaining medium was removed with 1X DPBS, and 6 ml of serum-free medium was added to each plate, followed by cell starvation for 24 hours. .

After the above process was added to the compound corresponding to the appropriate concentration of each compound determined in the cytotoxicity experiment of Example 2, and then incubated for another 2 hours. Then, human recombinant EGF was added to each plate to 20 ng / ml, and then stimulated by incubating for 10 minutes.

Remove all media from each plate, wash each plate twice with cold 1X DPBS, remove any remaining 1X DPBS, and then use 1X RIPA buffer (1 mM PMSF, protease inhibitor, phosphatase inhibitor) previously iced. 400 μl each was added, and then left on ice for 10 minutes. If cells were seen some distance apart, scrape the plates and scrape the plates to collect cell lysates and transfer them into pre-cooled 1.5 ml epi-tubes. And centrifugation was performed at 4 ℃ for 10 minutes at 10000 rpm.

After centrifugation, the pellets were discarded and only the supernatant was placed in ice on fresh epi-tubes. Then, in order to obtain only BMX protein in cell lysates, 2 μg of anti-BMX (Santa Cruz, sc-8874), an antibody against BMX, was placed in a tube and then rotated by hand for a while. The tube was placed in a rotator in the fridge and rotated for 3 hours at a speed of 20 rpm. A / G agarose beads (Santa Cruz, sc-2003) were mixed well in a 20 μl tube and screened with O / N in the refrigerating chamber to screen out BMX protein and antibody complexes. The next morning, each tube was taken out and centrifuged for 30 seconds using a mini centrifuge. The supernatant was carefully removed leaving about 100 μl of solution. 400 μl of cold 1X RIPA buffer was added and mixed carefully, followed by centrifugation for 30 seconds to remove the beads and components other than BMX. After repeating this process three times in total, 2X protein sample buffer (including mercaptoethanol or DTT) was added to the remaining solution and boiled in boiling water for 5 minutes. 40 μl was loaded onto 10% SDS-gel and electrophoresis was performed for 1 hour and a half at 100V.

The electrophoresis gel as described above was installed with a PVDF membrane filled with methanol in a cassette of a transfer kit used for western blotting and transferred for 1 hour and a half at 100V. Transfer membrane was washed with 1X TBST for a while, incubated with shaking for 1 hour at room temperature in 5% BSA buffer solution. To the solution diluted 4G10 (Abcam) in a blocking buffer (blocking buffer) 1: 500, the membrane obtained in the above-described process was put and incubated for 2 hours at room temperature. The membrane was washed four times for 10 minutes with 10 ml of 1 × TBST and reacted for 1 hour at room temperature with a solution of anti-mouse-conjugate HRP, a secondary antibody, diluted 1: 1000 in blocking buffer.

The membrane reacted as described above was washed four times with 10 ml of 1 × TBST for 10 minutes. After removing the remaining 1 × TBST from the membrane, the membrane was immersed in an ECL solution in the dark for 1 minute and exposed to an x-ray film. The x-ray film was developed, washed in tap water and dried in a dry oven. As shown in Figure 20, when the treatment of dasatinib was confirmed that the amount of phosphorylated BMX (phospho-Bmx) is reduced by inhibiting the activity of BMX, the anticancer of the present invention is a candidate compound for inhibition of activity against BMX Even when four candidate compounds were treated, it was confirmed that the activity of BMX was evenly reduced.

Although the present invention has been described with reference to the above embodiments, the present invention is not limited thereto. Those skilled in the art can make modifications and changes without departing from the spirit and scope of the present invention, and it will be appreciated that such modifications and changes also belong to the present invention.

Claims (6)

1. JFD00244, Tetrindole mesylate (Tetrindole mesylate), 5-nonyloxytryptamine oxalate (5-Nonyloxytryptamine oxalate) or clofazimine (Clofazimine) pharmaceutical composition for preventing and treating prostate cancer.
2. The method of claim 1,

   A pharmaceutical composition for preventing and treating prostate cancer, characterized by inhibiting the activity of BMX (BMX non-receptor tyrosine kinase).
3. The method according to claim 1 or 2,

   A pharmaceutical composition for preventing and treating prostate cancer, characterized in that it is formulated as an oral dosage form of tablets, pills, hard and soft capsules, solutions, suspensions, emulsifiers, syrups, granules, or elixirs.
4. The method according to claim 1 or 2,

   It is administered by a parenteral administration mode selected from the group consisting of intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, topical administration, intranasal administration, pulmonary administration, rectal administration and intrathoracic administration Pharmaceutical composition for preventing and treating prostate cancer.
5. The method according to claim 1 or 2,

   A pharmaceutical composition for preventing and treating prostate cancer, comprising clopazimin as an active ingredient.
6. The method according to claim 1 or 2,

   A pharmaceutical composition for preventing and treating prostate cancer, comprising tetridol mesylate as an active ingredient.

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