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WO2019066469A1 - Utilisation de fébuxostat ou de topiroxostat en tant qu'agent pour la prévention et le traitement de métastases cancéreuses - Google Patents

Utilisation de fébuxostat ou de topiroxostat en tant qu'agent pour la prévention et le traitement de métastases cancéreuses Download PDF

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Publication number
WO2019066469A1
WO2019066469A1 PCT/KR2018/011386 KR2018011386W WO2019066469A1 WO 2019066469 A1 WO2019066469 A1 WO 2019066469A1 KR 2018011386 W KR2018011386 W KR 2018011386W WO 2019066469 A1 WO2019066469 A1 WO 2019066469A1
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WO
WIPO (PCT)
Prior art keywords
cancer
pharmaceutically acceptable
group
metastasis
febuxostat
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/KR2018/011386
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English (en)
Korean (ko)
Inventor
김용림
최순연
오세현
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.)
Kyungpook National University Hospital
Industry Academic Cooperation Foundation of KNU
Original Assignee
Kyungpook National University Hospital
Industry Academic Cooperation Foundation of KNU
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Filing date
Publication date
Priority claimed from KR1020180005667A external-priority patent/KR102036355B1/ko
Application filed by Kyungpook National University Hospital, Industry Academic Cooperation Foundation of KNU filed Critical Kyungpook National University Hospital
Publication of WO2019066469A1 publication Critical patent/WO2019066469A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole

Definitions

  • the present invention relates to novel uses of febuxostat or topiroxostat and more particularly to the use of a compound selected from the group consisting of peroxostart, topiroxorstart and pharmaceutically acceptable salts thereof, Which one .
  • a pharmaceutical composition for prevention and treatment of cancer which inhibits cancer metastasis and contains at least one effective ingredient.
  • metastasis is the spread of cancer cells from primary cancer to other organs to form new cancers. Because metastasis is a major threat to life in a variety of cancer patients, preventing or controlling metastasis is an important goal in cancer research. When cancer is metastasized, the effectiveness of known chemotherapy methods is reduced. Clinically, the entire process of cancer metastasis has not yet been fully understood, but Epi thelial-Mesenchymal Transmission (EMT) has been recognized as an important concept in cancer metastasis (Sarah Heerboth et al ., EMT and tumor metastasis, Cl in Trans 1 Med. 2015; 4: 6.). Also, Wnt signaling pathway factors involved in cancer metastasis and their roles have been identified.
  • EMT Epi thelial-Mesenchymal Transmission
  • the inventors of the present invention conducted studies on cancer metastasis-inhibiting compounds, and confirmed that Pebuksotast or Topiroxastat specifically inhibited cancer cell migration and cancer metastasis, Completed.
  • Another object of the present invention to provide a page-start bukso 1511 ⁇ 6) «)), toffee rokso start (topiroxostat) and their pharmaceutically acceptable salt thereof for the manufacture of a therapeutic preparation for the cancer.
  • Another object of the present invention is to provide an effective amount of a composition comprising, as an active ingredient, at least one selected from the group consisting of topoisomerase (topoisoxin), topiroxostat and pharmaceutically acceptable salts thereof And administering to a subject in need thereof a method for treating cancer. It is still another object of the present invention to provide the use of febuxostat, topi roxostat and pharmaceutically acceptable salts thereof for producing an agent for inhibiting cancer metastasis.
  • topoisomerase topoisoxin
  • topiroxostat pharmaceutically acceptable salts thereof
  • Another object of the present invention is to provide an effective amount of a composition comprising, as an active ingredient, at least one selected from the group consisting of febuxostat, topiroxostat and pharmaceutically acceptable salts thereof.
  • a composition comprising, as an active ingredient, at least one selected from the group consisting of febuxostat, topiroxostat and pharmaceutically acceptable salts thereof.
  • the present invention provides a cancer metastasis comprising at least one member selected from the group consisting of Pebuksotast, Topi Roxostat and a pharmaceutically acceptable salt thereof as an active ingredient
  • a pharmaceutical composition for prevention and treatment of cancer is composed of at least one member selected from the group consisting of pemphigus starch, topiroxorstart, and pharmaceutically acceptable salts thereof.
  • the present invention also provides a pharmaceutical composition for prevention and treatment of cancer, which is essentially composed of at least one member selected from the group consisting of pemphigus starch, topiary roxostat and pharmaceutically acceptable salts thereof. do.
  • the present invention provides a cancer-inhibiting food composition comprising at least one selected from the group consisting of Pebuksotsta, Topi Roxostat, and a pharmaceutically acceptable salt thereof as an active ingredient .
  • the present invention also relates to a method for treating cancer, which comprises at least one member selected from the group consisting of pemphigus starch, topiroxorstart, and pharmaceutically acceptable salts thereof.
  • a food composition for inhibiting metastasis is provided.
  • the present invention also provides a food composition for inhibiting cancer metastasis which is essentially composed of at least one member selected from the group consisting of pemphigus starch, topiroxstart, and pharmaceutically acceptable salts thereof.
  • the present invention provides the use of febuxostat, topiroxostat and pharmaceutically acceptable salts thereof for preparing a therapeutic agent for cancer.
  • the invention is Fe bukso start (febuxostat), toffee rokso start (topi roxostat) and those of the pharmaceutically acceptable than any one, selected from the group consisting of salts effective ingredient To a subject in need thereof an effective amount of a composition comprising the compound of the present invention.
  • the present invention provides the use of febuxostat, topiroxostat and pharmaceutically acceptable salts thereof for producing an agent for inhibiting cancer metastasis.
  • the present invention provides a pharmaceutical composition containing at least one selected from the group consisting of febuxostat, topiroxostat and pharmaceutically acceptable salts thereof as an active ingredient Which comprises administering an effective amount of the composition to a subject in need thereof.
  • the present inventors have found that in vivo cancer metastasis models can be divided into two categories: It was confirmed that topiroxorstart specifically inhibited the metastasis of cancer cells and it was found that the behavior of the factors associated with the metastasis in the EMT and Wnt signaling systems was controlled normally at the molecular level.
  • the use of such a pegylated starter and topiroxorstart for suppressing cancer metastasis is disclosed for the first time in the present invention. Accordingly, the present invention provides a method for inhibiting cancer metastasis of pemphigus starch, topiroxorstart, and pharmaceutically acceptable salts thereof; A composition for preventing, ameliorating or treating cancer.
  • the present invention suppresses metastasis of tumor cells (cancer cells) and thus can be applied to various cancers.
  • cancer cells can be applied to various cancers.
  • cancer cells can be applied to various cancers.
  • breast cancer colorectal cancer
  • lung cancer liver cancer
  • esophageal cancer pancreatic cancer
  • gallbladder cancer kidney cancer
  • bladder cancer prostate cancer testicular cancer
  • cervical cancer endometrial cancer
  • choriocarcinoma choriocarcinoma
  • Head and neck cancer malignant melanoma
  • lymphoma lymphoma
  • aplastic anemia and the like.
  • the 'cancer prevention and treatment' in the composition of the present invention is carried out by inhibiting cancer cells.
  • 'febuxostat' refers to the IUPAC designation 2- [3-cyano-4- (2-methylpropoxy) henyl] -4-methy 1 -1,3-thi azo 1 e-5-carboxy 1 ic acid ', And has a structure represented by the following formula (1).
  • the phenol starting material may be commercially available or may be prepared by a chemical synthesis method known in the art, and examples of the synthesis include, but are not limited to, the following documents: US2013 / 0245278A1, Korean Patent No. 10-1630819, and the like.
  • 'topiroxostat' refers to the IUPAC name '4- (5-pyridin-4-y1-1H1,1,2,4-ri azo1-3-y1) -car bon itri 1 e 'and has the structure of the following formula (2).
  • the topical antioxidant may be purchased commercially or may be prepared by a chemical synthesis method known in the art. Examples of the synthesis of the topical antioxidant include, but are not limited to, CN105348264A, CN105566301A etc.
  • Pebusartot or topiroxorstant compound can be used as such or in the form of a salt, preferably a pharmaceutically acceptable salt.
  • a salt preferably a pharmaceutically acceptable salt.
  • the term " pharmaceutically acceptable " as used herein means physiologically acceptable and does not generally cause an allergic reaction or a similar reaction when administered to a human.
  • the salt include a pharmaceutically acceptable free acid ) Are preferred.
  • the free acid an organic acid and an inorganic acid can be used.
  • the organic acids include, but are not limited to, citric, acetic, lactic, tartaric, maleic, fumaric, formic, propionic, oxalic, tripleurooacetic, benzoic, gluconic, methosulfonic, glycolic, , Glutamic acid and aspartic acid.
  • Such inorganic acids include, but are not limited to, hydrochloric acid, bricic acid, sulfuric acid, and phosphoric acid.
  • pharmaceutically non-toxic salts include, but are not limited to, sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate chloride, bromide, But are not limited to, but are not limited to, but are not limited to, but are not limited to, but are not limited to, halides, halides, halides, halides, halides, halides, But are not limited to, lactose, sebacate, fumarate, maleate, butyne-1,4-dioate, nucleic acid-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, Methoxybenzoate, phthalate, terephthalate Wight, Benzene sulfonate, tetraene sulfonate, chlorobenz
  • the pharmaceutically acceptable carrier may further include, for example, a carrier for oral administration or a carrier for parenteral administration.
  • Carriers for oral administration may include lactose, starch, salicylose derivatives, magnesium stearate, stearic acid, and the like.
  • the carrier for parenteral administration may contain water, a suitable oil, a saline solution, an aqueous glucose and a glycol, and may further contain a stabilizer and a preservative.
  • Suitable stabilizers include antioxidants such as sodium hydrogen sulfite, sodium sulfite or ascorbic acid.
  • Suitable preservatives include benzalkonium chloride, methyl- or propyl-paraben and chlorobutanol.
  • Other pharmaceutically acceptable carriers can be found in the following references (Remington's Pharmaceutical Sciences, 19th ed., Mack Publishing Company, Easton, PA, 1995).
  • the pharmaceutical composition of the present invention can be administered to mammals including humans by any method.
  • it can be administered orally or parenterally.
  • Parenteral administration methods include, but are not limited to, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual or rectal administration Lt; / RTI >
  • the pharmaceutical composition may be formulated into oral or parenteral formulations according to the route of administration as described above.
  • the composition of the present invention may be formulated using methods known in the art such as powders, granules, tablets, pills, sugar tablets, capsules, liquids, gels, syrups, slurries, suspensions, .
  • the oral preparation may be prepared by mixing the active ingredient (in the present invention, at least one selected from the group consisting of Pebuksotst, Topi Roxostat, and a pharmaceutically acceptable salt thereof) with a solid excipient, Tablets or tablets of the sugar can be obtained by milling and processing with a granular blend after adding suitable auxiliaries have.
  • excipients examples include sugars such as lactose, dextrose, sucrose, sorbic, mannitol, xyli, erythritol and maltitol and corn starch, wheat starch, rice starch and potato starch
  • Cells comprising rosin, gelatin, polyvinylpyrrolidone, and the like can be included in the cell, including cells, roots, methyl sal rosin, sodium carboxymethyl salicylose and hydroxypropyl methyl-sal rose.
  • crosslinked polyvinylpyrrolidone, agar, alginic acid or sodium alginate may optionally be added as a disintegrant.
  • the pharmaceutical composition of the present invention may further comprise an anti-aging agent, a lubricant, a wetting agent, a flavoring agent, an emulsifying agent and an antiseptic agent.
  • the preparation for parenteral administration may be formulated by a method known in the art in the form of injections, creams, lotions, external ointments, oil agents, moisturizers, gels, aerosols and nasal inhalers. These formulations are described in Remington's Pharmaceutical Science, 15th Edition, 1975. Mack Publishing Company, East on, Pennsylvania 18042, Chapter 87: Blaug, Seymour), a commonly known formulary for all pharmaceutical chemistries.
  • a preferable example of the preparation for parenteral administration may be an injecting agent.
  • suitable carriers for injections include, but are not limited to, solvents or dispersion media containing water, ethanol, polyols (such as glycerol, propylene glycol and liquid polyethylene glycol, etc.), mixtures thereof and / or vegetable oils . More preferred examples of suitable carriers include Hank's solution, Ringer's solution, phosphate buffered saline (PBS) containing triethanolamine or isotonic solutions such as sterilized water for injection, 10% ethanol, 40% propylene glycol and 5% Can be used.
  • PBS phosphate buffered saline
  • various antibacterial and antifungal agents such as parabens, chlorobutanol, phenol, sorbic acid, thimerosal and the like may be further included. Further, the injections may contain most of the weight, the horizontal isotonic agents such as sugars or sodium chloride cases.
  • the total effective amount of the compounds in the compositions of the present invention may be administered to a patient in a single dose and may be administered by a fractionated treatment protocol administered over a prolonged period of time in multiple doses have.
  • the pharmaceutical composition of the present invention may vary in the content of the active ingredient depending on the severity of the disease.
  • the preferred total dose of the compounds in the composition of the present invention is about 0.01 to 1,000 mg daily dose, 0.1 to 100 mg is known.
  • the dose of the compounds is not limited to the route of administration and the number of treatments of the pharmaceutical composition Considering various factors such as the patient's age, body weight, health condition, sex, severity of disease, diet and excretion rate, the effective dose for the patient is determined.
  • the pharmaceutical composition according to the present invention is not particularly limited to its formulation, administration route and administration method as long as the effect of the present invention is exhibited.
  • the food composition of the present invention includes all forms such as functional foods, nutritional supplements, health foods, and food additives.
  • Food compositions of this type may be prepared in a variety of forms according to conventional methods known in the art.
  • the health food may be prepared in the form of tea, juice and drink containing the above compounds, and liquefied, capped and powdered for ingestion.
  • the above compounds can be administered in combination with anticancer (ant Tumor growth inhibition), or a known substance or active ingredient known to have an inhibitory effect on cancer metastasis.
  • Functional foods also include but are not limited to beverages (including alcoholic beverages), fruits and processed foods (e.g., canned fruits, jams, maamarade, etc.), fish, meat and processed foods (Eg butter, chewing), edible vegetable oil, margarine (for example, sausage, noodles, etc.), breads and noodles (eg udon, buckwheat noodles, ramen noodles, spaghetti, macaroni, , Vegetable protein retort foods, roasted foods, various seasonings (e.g., soybean paste, soy sauce, sauces, etc.). Further, in order to use the above-mentioned compounds in the form of food additives, they may be used in the form of powders or concentrates.
  • the preferred content of the compounds in the food composition of the present invention is not particularly limited, but is preferably 0.01 to 50% by weight in the finally prepared food.
  • the present invention provides the use of febuxostat, topiroxostat and pharmaceutically acceptable salts thereof for preparing a therapeutic agent for cancer.
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising an effective amount of a composition comprising, as an active ingredient, at least one selected from the group consisting of febuxostat, topiroxostat and pharmaceutically acceptable salts thereof, Or a pharmaceutically acceptable salt thereof.
  • the present invention provides the use of febuxostat, topiroxostat and pharmaceutically acceptable salts thereof for producing an agent for inhibiting cancer metastasis.
  • the present invention relates to a method of treating an effective amount of a composition
  • a composition comprising, as an active ingredient, at least one selected from the group consisting of febuxostat, topiroxostat and pharmaceutically acceptable salts thereof, Or a pharmaceutically acceptable salt thereof.
  • the "effective amount” of the present invention refers to an amount that, when administered to an individual, is indicative of improvement, treatment, prevention, detection, diagnosis, or inhibition of cancer or metastasis of cancer, , Particularly an animal including a human, and may be an animal-derived cell, tissue, organ, and the like. The subject may be a patient requiring the effect.
  • the term " treatment " of the present invention broadly refers to ameliorating the symptoms of cancer or cancer, which may include curing, substantially preventing, or ameliorating the condition, But is not limited to, relieving, curing or preventing symptoms or most symptoms.
  • " compri sing " of the present invention is used in the same way as " containing " or " characterized ", and does not exclude any additional component elements or method steps Do not.
  • the term " consisting of " means excluding any additional elements, steps or components not otherwise mentioned.
  • the term " essential consent of " as used herein is intended to encompass, in the scope of the invention, a component element or step as well as component elements or steps which do not materially affect its basic properties, .
  • FIG. 1A shows the in vivo luminescence image changes (lesion sites) in the order of time in each experimental group
  • FIG. 1B shows the result of comparative evaluation of the degree of cancer metastasis after excision of organs in each experimental group after the experiment
  • Degree. lc indicates the extent of cancer metastasis to other organs in each experimental group
  • Id shows the results of H & E staining for cancer metastasis in lung and liver tissues in each experimental group.
  • FIGS. 2A to 2C show the expression pattern of EMT-related factors f ibronectin (FIG. 2A), E-cadherin (FIG. 2B) and vimentin (FIG. 2C) for cancer metastasis in each experimental group.
  • FIGS. 3A and 3B show the expression pattern of AQP5 (FIG. 3A) and MMP9 (FIG. 3B), which are factors involved in cancer cell migration, comparatively for each experimental group.
  • FIGS. 4A and 4B show the expression pattern of Wnt signal pathway-related factors Wnt7a (FIG. 4A) and ⁇ -catenin (FIG. 4B) for cancer metastasis relative to each experimental group.
  • FIG. 5 shows the results of evaluation of cancer cell survival rate by using MTT assay for breast cancer cells induced to metastasize to LDL (as a positive control, PE isostatic or LDL alone treatment group is used).
  • FIGS. 6A and 6B show the results of evaluating the cancer cell mobility of breast cancer cells induced by metastatic status into LDL using the Wound healing assay method (IncuCyte® Scratch found cell migration system) (Fig. 6A) and the final quantitative result (Fig. 6B) with time.
  • FIGS. 7A and 7B show the results of transwell migration assay of breast cancer cells induced by metastasis to LDL using the transwell migration assay. 7a) and final quantification results (Fig. 7b).
  • FIG. 8 shows the results of evaluating the cancer cell mobility according to the concentration of the starting cells in the breast cancer cells induced by the metastatic state to LDL using the Wound healing assay (IncuCyte® Scratch Wound Cell Migration System).
  • FIGS. 9A and 9B show the results of evaluating the cancer cell mobility after treatment with toxitosotrost in Wound healing assay (IncuCyte® Scratch Wound Cell Migration System) for breast cancer cells induced to metastatic state by LDL (FIG. 9A) and the final quantitative result (FIG. 9B) over time.
  • Wound healing assay IncuCyte® Scratch Wound Cell Migration System
  • FIGS. 9A and 9B show the results of evaluating the cancer cell mobility after treatment with toxitosotrost in Wound healing assay (IncuCyte® Scratch Wound Cell Migration System) for breast cancer cells induced to metastatic state by LDL (FIG. 9A) and the final quantitative result (FIG. 9B) over time.
  • mice Four-week-old female BALB / c mice were obtained from SAMTACO bioscience CO., LTD, Korea. The mice were divided into two groups (normal diet D10001 control rodent diet, Research Diets Inc.) and gourcoleste diet group (gourcoleste for feed D12336, Research Diets Inc.), and gourcoleste was fed for 6 weeks. On the 4th week after the high cholesterol diet, Luc-4T1 breast cancer cell line (BW124087, PerkinElmer, lxi0 6 cell suspended in 100 ⁇ RPMI) was injected into the mammary fat pad of BALB / Mouse model was constructed. In addition, Febuxost at (Catalog No.
  • Incubation patterns were observed in vitro through the IncuCyte® Scratch Wound Cell Migration System. Briefly, a 4T1 breast cancer cell line (ATCC®, CRL2539 TM) was seeded on a 96-well plate at 1.2 ⁇ 10 4 cells and then seeded at 96-pin A scratch was made using a WounderMaker (IncuCyte). The debris was removed with PBS, and real-time cells were measured at intervals of 4 hours while being treated with 50 ⁇ g / m LDL (Merk) and 50 ⁇ M Febuxostat (Calbiochem) or 50 ⁇ M Toporoxostat (Calbiochem) for 48 hours. The relative wound density was expressed as a percentage of the control.
  • 4T1 breast cancer cell lines (ATCC®, CRL2539 TM) were dispensed into 96-well plates at 7 ⁇ 10 3 cells / well, and then treated with LDL (Merk) and 50 ⁇ M Febuxostat (Calbiochem) for 24 hours. After the reaction, the cells were repelled for 4 hours in 500/3 MTT (Amresco) solution, and the stained cells were dissolved using 200 // DMSO (Amersco) and then measured at 570 nm absorbance. The graphs are expressed as a percentage of the control.
  • Real-time PCR Total RA was extracted from the primary tumor tissue using TRIzol (Invitrogen), and cDNA was synthesized using PrimeScript TM 1 st strand cDNA synthesis kit (Takara). The synthesized cDNA was performed by qPCR using Power SYBR® "Green PCR Master Mix ( Thermo) and the reaction, StepOne Plus Real-time PCR system (Appl ied Biosystems) was. Banung qPCR conditions were 30 seconds at 95 ° C 40 cycles denaturation and annealing and polymerization for 1 min at 60 ° C. The primer The sequence is shown in Table 1 below.
  • Example 1 In vivo inhibition of metastasis
  • Example 2 Confirmation of specific inhibitory effect on cancer cell metastasis (migration) in vitro
  • phevocastat acts specifically to control the metastasis of cancer cells
  • 4wt Breast cancer cell lines were treated with phenobarbstart alone or with LDL low density lipoprotein cholesterol) was treated to induce metastatic status, treated with Pevasostat and MTT assay, Wound healing assay and migration assay.
  • RTI ID 0.0 &gt
  • mni assay, < / RTI &gt Figs. 6A, 6B, 7A and 7B.
  • the effect of inhibiting the migration of cancer cells by the pegasus starter was dose-dependent (Fig. 8).
  • Example 3 In vitro cancer cell metastasis-specific inhibitory effect of topiroxlostat
  • the 4T1 breast cancer cell line was cultured in the same manner as in Example 2, Roxastat was treated alone or treated with low density lipoprotein cholesterol (LDL) to induce a metastatic state, followed by topical antioxidant treatment and Wound healing assay.
  • LDL low density lipoprotein cholesterol
  • the present invention relates to a novel use of febuxostat or topiroxostat, and more particularly, to a novel use of febuxostat or topiroxostat, A pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable salt thereof, as an active ingredient, to a pharmaceutical composition for prevention and treatment of cancer. Since febuxostat and topiroxostat have a remarkable effect of specifically inhibiting the metastasis of cancer, they provide a new means for cancer prevention and treatment, and thus are highly industrially applicable in the pharmaceutical industry and the like .

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Abstract

La présente invention concerne une nouvelle utilisation du fébuxostat ou de topiroxostat et, plus spécifiquement, une composition pharmaceutique pour la suppression de métastases cancéreuses et la prévention et le traitement du cancer, la composition pharmaceutique contenant, en tant que principe actif, au moins un élément choisi dans le groupe constitué par le febuxostat, le topiroxostat, et des sels pharmaceutiquement acceptables associés. Le fébuxostat ou le topiroxostat a un effet remarquable de suppression spécifique de métastases cancéreuses, constituant ainsi un nouveau moyen de prévention et de traitement du cancer.
PCT/KR2018/011386 2017-09-27 2018-09-27 Utilisation de fébuxostat ou de topiroxostat en tant qu'agent pour la prévention et le traitement de métastases cancéreuses Ceased WO2019066469A1 (fr)

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