[go: up one dir, main page]

WO2014065537A1 - Composition pharmaceutique pour la prévention et le traitement du cancer de la prostate - Google Patents

Composition pharmaceutique pour la prévention et le traitement du cancer de la prostate Download PDF

Info

Publication number
WO2014065537A1
WO2014065537A1 PCT/KR2013/009283 KR2013009283W WO2014065537A1 WO 2014065537 A1 WO2014065537 A1 WO 2014065537A1 KR 2013009283 W KR2013009283 W KR 2013009283W WO 2014065537 A1 WO2014065537 A1 WO 2014065537A1
Authority
WO
WIPO (PCT)
Prior art keywords
prostate cancer
preventing
pharmaceutical composition
administration
bmx
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/KR2013/009283
Other languages
English (en)
Korean (ko)
Inventor
김대중
정난영
최정숙
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
CGK BIO Inc
Original Assignee
CGK BIO Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by CGK BIO Inc filed Critical CGK BIO Inc
Publication of WO2014065537A1 publication Critical patent/WO2014065537A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4995—Pyrazines or piperazines forming part of bridged ring systems

Definitions

  • 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. .
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Tyrosine kinase which is responsible for signal transduction of cells, is involved in the transformation of prostate epithelial cells and tumor progression.
  • BMX BMX non-receptor tyrosine kinase
  • PI3K / AKT a typical signaling pathway involved in the cancer metastasis process when stimulated with EGF (epithelial growth factor).
  • EGF epidermal growth factor
  • 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).
  • TNF Tumor Necrosis Factor
  • 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. .
  • 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.
  • JFD00244 is a compound having Formula 1 below, tetralindol mesylate below Formula 2, 5-nonyloxytrytamine oxalate below Formula 3 and clofazimin below 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).
  • the pharmaceutical composition for preventing and treating prostate cancer of the present invention includes clofazimin as an active ingredient.
  • compositions 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.
  • diluents e.g., lactose
  • 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.
  • 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.
  • 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.
  • compositions for preventing and treating prostate cancer of the present invention 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Lopac P08-F02 represents JFD00244
  • Tocris P03-F11 represents tetralindol mesylate
  • Tocris P04-H11 represents 5-nonyloxytrytamine oxalate
  • 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.
  • 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.
  • BMX BMX UniProt protein knowledge database
  • BMX Ensembl genome database BMX Ensembl genome database
  • FP fluorescent protein
  • 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 1280TM Small Scale (International Version) (Sigma-aldrich), by MicroSource US Collection and International Drug Collection, FDA approved drug library from Enzo, and the like.
  • 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.
  • MNP to which dasatinib, which is a compound that binds to the BMX protein is bound Magnetic Nano Particle
  • MNP to which dasatinib, which is a compound that binds to the BMX protein is bound Magnetic Nano Particle
  • the fluorescent protein-labeled BMX protein and Dasatinib bound to MNP Magnetic Nano Particle
  • MNP Magnetic Nano Particle
  • the fluorescent pattern of EGFP also overlaps with the magnetization pattern according to the binding of MNP-Dasatinib-BMX protein. Will appear.
  • 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.
  • MNP magnetic nanoparticle
  • 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).
  • 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 1-1 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 1-1 and Example 1-2 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).
  • 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.
  • 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.
  • control compounds eg, cathodex, dasatinib, lapatinib
  • 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.
  • Example 1 The four candidate compounds selected at -3 were slightly different in sensitivity depending on the cell line.
  • Example 3 In vitro cell proliferation inhibition experiment on prostate cancer cell line
  • 22Rv1 cell lines were seeded in 96-well plates at 2 ⁇ 10 4 cells / well and then incubated for one day.
  • 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.
  • EGF 20 ng / ml
  • control compounds e.g., cathodex, dasatinib, lapatinib
  • anticancer candidate compounds were added according to the concentration determined in Example 2, and then incubated for 48 hours in a CO 2 incubator.
  • 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.
  • 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.
  • 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. .
  • each tube was taken out and centrifuged for 30 seconds using a mini centrifuge. The supernatant was carefully removed leaving about 100 ⁇ l of solution. 400 ⁇ l 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 ⁇ l was loaded onto 10% SDS-gel and electrophoresis was performed for 1 hour and a half at 100V.
  • 2X protein sample buffer including mercaptoethanol or DTT
  • 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.
  • 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.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une composition pharmaceutique pour la prévention et le traitement du cancer de la prostate. La composition pharmaceutique pour la prévention et le traitement du cancer de la prostate de la présente invention comprend JFD00244, mésylate de tétrindole, oxalate de 5-nonyloxytryptamine ou clofazimine comme principe actif. La composition pharmaceutique pour la prévention et le traitement du cancer de la prostate de la présente invention présente des effets anticancéreux d'élimination sélective de cellules cancéreuses de la prostate par l'inhibition de l'activité de BMX, et l'inhibition de la prolifération des lignées cellulaires cancéreuses de la prostate. Par conséquent, la composition pharmaceutique pour la prévention et le traitement du cancer de la prostate de la présente invention peut surmonter les problèmes et les limitations de la thérapie hormonale classique et la radiothérapie pour le cancer de la prostate, et peut être appliquée en tant que médicament anticancéreux ciblé pour le cancer de la prostate.
PCT/KR2013/009283 2012-10-23 2013-10-17 Composition pharmaceutique pour la prévention et le traitement du cancer de la prostate Ceased WO2014065537A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2012-0117695 2012-10-23
KR1020120117695A KR20140051555A (ko) 2012-10-23 2012-10-23 전립선암 예방 및 치료용 약학 조성물

Publications (1)

Publication Number Publication Date
WO2014065537A1 true WO2014065537A1 (fr) 2014-05-01

Family

ID=50544869

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2013/009283 Ceased WO2014065537A1 (fr) 2012-10-23 2013-10-17 Composition pharmaceutique pour la prévention et le traitement du cancer de la prostate

Country Status (2)

Country Link
KR (1) KR20140051555A (fr)
WO (1) WO2014065537A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118634224A (zh) * 2024-06-28 2024-09-13 大连医科大学附属第二医院 常绿钩吻碱在制备用于治疗前列腺癌的药物中的新用途

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101675664B1 (ko) 2015-01-30 2016-11-11 경희대학교 산학협력단 전립선암 예방 또는 치료용 조성물
KR102155125B1 (ko) 2015-07-17 2020-09-11 경희대학교 산학협력단 악성 중피종 예방 또는 치료용 조성물
KR20180085387A (ko) 2016-12-27 2018-07-27 경희대학교 산학협력단 Trail 저항성 암 예방 또는 치료용 조성물

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5763443A (en) * 1994-04-05 1998-06-09 Universiteit Van Pretoria MDR resistance treatment and novel pharmaceutically active riminophenazines
US20040067952A1 (en) * 2001-07-17 2004-04-08 Morris David Lawson Method and composition for treatment of cancer
WO2008141189A1 (fr) * 2007-05-09 2008-11-20 Elixir Pharmaceuticals, Inc. Composés modulant la ghréline et leurs combinaisons
US20110251144A1 (en) * 2008-09-16 2011-10-13 Massachusetts Institute Of Technology Molecular modulators of the wnt/beta-catenin pathway

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5763443A (en) * 1994-04-05 1998-06-09 Universiteit Van Pretoria MDR resistance treatment and novel pharmaceutically active riminophenazines
US20040067952A1 (en) * 2001-07-17 2004-04-08 Morris David Lawson Method and composition for treatment of cancer
WO2008141189A1 (fr) * 2007-05-09 2008-11-20 Elixir Pharmaceuticals, Inc. Composés modulant la ghréline et leurs combinaisons
US20110251144A1 (en) * 2008-09-16 2011-10-13 Massachusetts Institute Of Technology Molecular modulators of the wnt/beta-catenin pathway

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118634224A (zh) * 2024-06-28 2024-09-13 大连医科大学附属第二医院 常绿钩吻碱在制备用于治疗前列腺癌的药物中的新用途

Also Published As

Publication number Publication date
KR20140051555A (ko) 2014-05-02

Similar Documents

Publication Publication Date Title
US8691799B2 (en) Materials and methods for treatment of cancer and identification of anti-cancer compounds
Chou et al. A chemical probe inhibitor targeting STAT1 restricts cancer stem cell traits and angiogenesis in colorectal cancer
WO2020085642A1 (fr) Composition pharmaceutique permettant la prévention ou le traitement du cancer, contenant du n-1h-benzimidazol-2-yl-3-(1h-pyrrole-1-yl) benzamide en tant que principe actif
WO2014065537A1 (fr) Composition pharmaceutique pour la prévention et le traitement du cancer de la prostate
Paradisi et al. Netrin-1, a missing link between chronic inflammation and tumor progression
CN101189241A (zh) 噻吩并吡啶衍生物、喹啉衍生物和具有c-Met自体磷酸化抑制活性的喹唑啉衍生物
Schumacher et al. Death associated protein kinase as a potential therapeutic target
Li et al. Anthraquinone derivative C10 inhibits proliferation and cell cycle progression in colon cancer cells via the Jak2/Stat3 signaling pathway
Pingwara et al. Interferon lambda 2 promotes mammary tumor metastasis via angiogenesis extension and stimulation of cancer cell migration
Shen et al. MicroRNA-125a regulates proliferation and apoptosis of acute myeloid leukemia through targeting NF-κB pathway.
Jiang et al. Multifunctions of CRIF1 in cancers and mitochondrial dysfunction
CN108309975A (zh) 小分子化合物wb460在制备治疗胰腺癌药物中的应用
CN115957203B (zh) 一种可用于降低膀胱癌细胞耐药性的化合物、组合物及其应用
CN111718296B (zh) 靶向cd133的小分子化合物ly335979在制备抗肿瘤药物中的应用
CN115581693A (zh) 香叶木素在抑制和治疗胃癌中的用途
Zhao et al. Benzoyl-xanthone derivative induces apoptosis in MCF-7 cells by binding TRAF6
CN108553462B (zh) 一种吡啶类衍生化合物在制备治疗癌症药物中的应用
Chen et al. Metachromin C, a marine-derived natural compound, shows potential in antitumor activity
CN103893182A (zh) 一类set蛋白小分子抑制剂及其用途
WO2025023774A1 (fr) Composition pour inhiber l'angiogenèse induite par vegf, comprenant un peptide de liaison à ccl8
CN107529558B (zh) 多聚核苷酸-5’激酶-3’磷酸酶的新应用
Peng et al. de-O-methyllasiodiplodin from Ludwigia hyssopifolia causes death of human liver cancer cells through the mitochondrial apoptotic, Akt/NF-κB and STAT3 pathway in vitro
CN116602948B (zh) 一种可用于降低膀胱癌细胞耐药性的化合物、组合物及其应用
CN115572266B (zh) 一种蛋白抑制剂、一种试剂组及其应用
Cai et al. Astragalus Polysaccharide Regulates Proliferation, Migration and Invasion of Lung Cancer Cells via Janus Kinase/Signal Transducer and Activator of Transcription Signaling Pathway.

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 13849599

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205A DATED 02/09/2015)

122 Ep: pct application non-entry in european phase

Ref document number: 13849599

Country of ref document: EP

Kind code of ref document: A1