[go: up one dir, main page]

WO2019103203A1 - Nouveau peptide et composition le comprenant - Google Patents

Nouveau peptide et composition le comprenant Download PDF

Info

Publication number
WO2019103203A1
WO2019103203A1 PCT/KR2017/013532 KR2017013532W WO2019103203A1 WO 2019103203 A1 WO2019103203 A1 WO 2019103203A1 KR 2017013532 W KR2017013532 W KR 2017013532W WO 2019103203 A1 WO2019103203 A1 WO 2019103203A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
peptide
cancer
treating
fibrosis
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/KR2017/013532
Other languages
English (en)
Korean (ko)
Inventor
김상재
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.)
GemVax and Kael Co Ltd
Original Assignee
GemVax and Kael Co Ltd
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 GemVax and Kael Co Ltd filed Critical GemVax and Kael Co Ltd
Priority to KR1020207010376A priority Critical patent/KR102436084B1/ko
Priority to PCT/KR2017/013532 priority patent/WO2019103203A1/fr
Publication of WO2019103203A1 publication Critical patent/WO2019103203A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the present invention relates to novel peptides and compositions containing the same, and more particularly to compositions effective for anti-inflammation, anti-fibrosis, wound healing, skin improvement and chemotherapy, including novel peptides.
  • TNF Tumor necrosis factor
  • TNF-a Tumor necrosis factor
  • TACE tumor necrosis factor-converting enzyme
  • Fibrosis is a disease in which abnormal formation, accumulation and deposition of extracellular matrix by fibroblasts occurs. It refers to an abnormal accumulation of collagen matrix due to injury or inflammation that changes the structure and function of various tissues. Regardless of the location of the onset of fibrosis, most of the etiology of fibrosis involves excessive accumulation of the collagen matrix that replaces normal tissue. Fibrosis, particularly in the kidneys, liver, lungs, heart, bone or bone marrow, and skin, can lead to organ dysfunction and even death in the worst case. The fibroblasts function to form a precursor of extracellular matrix in a normal state to form a fibrous tissue.
  • the extracellular matrix which is the intercellular material of the connective tissue, is present in the form of proteins such as fibronectin, laminin, chondronectin, and collagen.
  • TGF- ⁇ plays a diverse role in the abnormal production and accumulation of extracellular matrix by fibroblasts such as cell proliferation, inflammation reaction, and cancer cell metastasis, and many cellular signaling pathways and targets are identified have.
  • studies on TGF- ⁇ have been carried out in many disease models. Fibrotic diseases and cancers are the most active areas of research and drug development.
  • TGF- ⁇ is a cell growth regulator, which induces or restricts cell proliferation and plays an important role in the pathogenesis of various diseases including cancer, heart disease and diabetes, and various physiological activities have been reported.
  • TGF-beta For example, inhibition of TGF-beta synthesis, inhibition of TGF-beta antagonist, inhibition of PDGF (Platelet-Derived Growth Factor) antagonist, p38 MAP kinase inhibitor (inhibiting cell proliferation signal transduction enzyme), and anti-inflammation (suppression of TNF-alpha and MAPK production). Therefore, if a new medicinal composition capable of inhibiting TGF-beta more directly or interrupting the signal transduction process involving TGF-beta can be developed, prevention and treatment of various diseases and aging caused by fibrosis are performed You can do it.
  • PDGF Plateratived Growth Factor
  • the wound healing process is divided into four stages: inflammation, granulation, epithelialization, and fibroplasia.
  • inflammation the necessary cells (fibroblasts, epithelial cells, etc.) are activated.
  • fibroblasts deposit collagen, which increases collagen and matures the wound.
  • keratinocyte changes in the wound area, epithelial thickening of the defect, thickening of epithelium cells from the basal cells below the epidermis to the epidermis,
  • the collagen fibers form a collagenous matrix through the epithelializer to the fiber proliferators.
  • the collagen fibers form a collagenous matrix, which covers the wound-defective area. When this is done for a long time, the collagen fibers heal. Therefore, epithelial cell proliferation and collagen production may be one of the important mechanisms of wound healing and anti-aging.
  • the present inventors have developed novel peptides and discovered that they have the effects of anti-inflammation, anti-fibrosis, wound healing, skin improvement and anti-cancer through reduction of TNF- ⁇ and inhibition of TGF- ⁇ .
  • the object of the present invention is to provide novel peptides which are effective for anti-inflammation, anti-fibrosis, wound healing and anti-cancer, and compositions for preventing and treating diseases comprising the same.
  • the present invention provides a peptide comprising the amino acid sequence of SEQ ID NO: 1, or a peptide that is a fragment of the peptide sequence, or a pharmaceutically acceptable salt thereof.
  • the invention provides a anti-inflammatory composition comprising the peptide, or a pharmaceutically acceptable salt thereof.
  • the anti-inflammatory composition according to the present invention may be a anti-inflammatory composition having anti-inflammatory activity by inhibiting TNF- ⁇ .
  • the anti-inflammatory composition according to the present invention is useful for the treatment of inflammatory bowel disease such as rheumatoid arthritis, psoriasis, psoriatic arthritis, atopic dermatitis, ulcerative colitis and Crohn's disease, ankylosing spondylitis, multiple sclerosis, systemic lupus erythematosus (SLE) Related disease selected from the group consisting of chronic obstructive pulmonary disease (COPD), sepsis, endotoxic shock, hepatitis, and type 1 diabetes.
  • COPD chronic obstructive pulmonary disease
  • COPD chronic obstructive pulmonary disease
  • sepsis sepsis
  • endotoxic shock hepatitis
  • type 1 diabetes type 1 diabetes
  • the present invention also provides a composition for preventing, treating or ameliorating a body organ fibrosis comprising the peptide, or a pharmaceutically acceptable salt thereof.
  • the composition for preventing, treating or ameliorating the body organ fibrosis according to the present invention may be a composition characterized in that it has a body organ fibrosis inhibitory activity by inhibiting TJF-beta signaling.
  • the composition for preventing, treating or ameliorating the body organ fibrosis according to the present invention is a composition for preventing and treating fibrosis induced by at least one selected from the group consisting of cancer, administration of an anti-cancer agent, and radiation exposure .
  • the composition for the prevention, treatment or amelioration of the body organ fibrosis according to the present invention is used for the treatment of fibrosis of cancer cell tissue selected from the group consisting of pancreatic cancer, colon cancer, stomach cancer, prostate cancer, non-small cell lung cancer, breast cancer, melanoma and ovarian cancer Or a pharmaceutically acceptable salt thereof.
  • the invention also provides compositions for treating or improving wounds comprising the peptide, or a pharmaceutically acceptable salt thereof.
  • the composition for treating or improving wounds according to the present invention may be a composition having wound healing efficacy by inducing collagen synthesis.
  • composition for treating or improving wounds according to the present invention is useful for preventing skin diseases or worsening selected from the group consisting of skin wrinkles, skin dryness, scarring, skin exfoliation, epidermal burns, epidermal lacerations, Or treating a disorder or condition.
  • the composition may be a composition for improving skin condition comprising the at least one peptide, or a salt thereof.
  • the skin condition may be at least one of skin wrinkles, skin dryness, elasticity loss, and skin exfoliation due to aging of the skin.
  • the composition may be a cosmetic composition.
  • the composition may be an anticancer composition comprising the at least one peptide, or a salt thereof.
  • the invention also relates to a composition comprising the peptide, or a pharmaceutically acceptable salt thereof; And a kit for use for an efficacy of at least one of anti-inflammation, anti-fibrosis, anti-cancer, wound healing, and skin condition improvement, comprising instructions for initiating at least one of the dose, administration route, administration frequency and indications of the composition .
  • the present invention is also directed to a method of treating a subject in need of such an effect, wherein the composition comprises the peptide, or a pharmaceutically acceptable salt thereof, in one or more of the following: anti-inflammatory, anti-fibrotic, anti-cancer, wound healing, Inflammatory, fibrotic, cancerous, or wound comprising, a method of preventing or treating, or a method of improving skin condition.
  • the invention provides a novel use of said peptide, or a pharmaceutically acceptable salt thereof.
  • the use may be improvement, prevention and treatment of inflammation, fibrosis, cancer or wound.
  • the use may be for skin condition improvement.
  • the skin condition may be at least one of skin wrinkles, skin dryness, elasticity loss, and skin exfoliation due to aging of the skin. For example, as a cosmetic composition.
  • the present invention may be a peptide or a salt thereof for improving, preventing or treating inflammation, fibrosis, cancer or wound.
  • the peptides comprising the sequence of SEQ ID NO: 1 according to the present invention, or peptides thereof, have anti-inflammatory, anti-fibrotic, wound healing and anti-cancer efficacy and are useful for preventing or treating inflammation, fibrosis, Is expected to provide.
  • FIG. 1 shows the results obtained by treating the LPS-treated THP-1 cell line with the novel peptide SEQ ID NO: 1 (ALTSKLRG) and the positive control peptide SEQ ID NO: 2 (ALTSKLRA) with each concentration (1, 5, MRNA expression level of the cells was measured by RT-qPCR, and then the inhibition ratio was plotted.
  • ALTSKLRG novel peptide SEQ ID NO: 1
  • ALTSKLRA positive control peptide SEQ ID NO: 2
  • FIG. 2 shows the results of immunohistochemical staining of a THP-1 cell line induced by LPS in which the novel peptide SEQ ID NO: 1 (ALTSKLRG) and the positive control peptide SEQ ID NO: 2 (ALTSKLRA) , A control group without any treatment, and a positive control group treated with estradiol (E2), and then measuring the amount of TNF- ⁇ by ELISA.
  • ALTSKLRG novel peptide SEQ ID NO: 1
  • ALTSKLRA positive control peptide SEQ ID NO: 2
  • FIG. 3 is a graph showing the results of immunohistochemical staining of HepG2 cell line with a control group treated with nothing, a fibrosis control group treated with TGF-? Alone, a positive control treated with TGF-? And SB43152, a novel peptide SEQ ID NO: 1 (ALTSKLRG) and a positive control peptide SEQ ID NO: ALTSKLRA) was treated with each concentration (1 and 10 ⁇ M), and the expression of the fibroblast markers phosphor-Smad 2/3, Smad 2/3 and the reference gene GAPDH was analyzed by Western blotting and image analyzer (Top) and the graph (bottom) showing the measurement.
  • ALTSKLRG novel peptide SEQ ID NO: 1
  • ALTSKLRA positive control peptide SEQ ID NO: ALTSKLRA
  • Fig. 4 shows the results of evaluation of the effect of the new peptide on the wound-induced animal model induced by wounding on SD rats, immediately after wounding and at intervals of 2 days, at a concentration of 100 ⁇ ⁇ / ml every 50 ⁇ ⁇ , , And the area of the wound on each 11 was measured together with a control group to which no treatment was applied.
  • FIG. 5 shows the results of evaluation of the effect of the new peptide on the 3rd and 5th days in the experimental group treated with 50 ⁇ l each of the new peptide at a concentration of 100 ⁇ g / ml immediately after the wound and at the 2-day interval in the wound-
  • the biopsies were performed two times and the tissues were stained with masson trichrome to measure the degree of collagen production with the average fluorescence intensity.
  • a novel peptide that comprises or is a fragment of SEQ ID NO: 1 (ALTSKLRG).
  • a novel peptide consisting of the sequence of SEQ ID NO: 1 (ALTSKLRG) is disclosed.
  • the molecular weight of the sequence of SEQ ID NO: 1 is 844.51.
  • the peptide disclosed herein comprises peptides which comprise or are a fragment of SEQ ID NO: 1 and at least one amino acid, at least two amino acids, at least three amino acids, at least four amino acids, at least five amino acids, at least six amino acids, More than two amino acids may be included.
  • the amino acid change is of a property that causes the physicochemical properties of the peptide to change.
  • amino acid changes such as improving the thermal stability of the peptide, altering the substrate specificity, changing the optimum pH, etc. can be performed.
  • amino acid includes D-isomers and modified amino acids as well as the 22 standard amino acids that are naturally incorporated into the peptide. Accordingly, in one aspect of the present invention, the peptide may be a peptide comprising a D-amino acid. In another aspect of the present invention, the peptide may include post-translationally modified non-standard amino acids and the like.
  • post-translational modifications include phosphorylation, glycosylation, acylation (including, for example, acetylation, myristoylation and palmitoylation), alkylation ), Carboxylation, hydroxylation, glycation, biotinylation, ubiquitinylation, changes in chemical properties (such as, for example, beta-depleted deamidation , Deamidation) and structural changes (e.g., formation of a disulfide bridge).
  • amino acid changes such as changes in amino acids, such as changes in amino groups, carboxy groups or side chains, caused by chemical reactions that take place during binding with crosslinkers to form peptide conjugates.
  • the peptides disclosed herein may be wild type peptides identified and isolated from natural sources.
  • the peptides disclosed herein may be artificial variants, including amino acid sequences in which one or more amino acids are substituted, deleted and / or inserted as compared to peptides that are fragments of SEQ ID NO: 1.
  • Amino acid changes in wild-type polypeptides as well as in artificial variants include conservative amino acid substitutions that do not significantly affect folding and / or activity of the protein.
  • conservative substitutions include, but are not limited to, basic amino acids (arginine, lysine and histidine), acidic amino acids (glutamic acid and aspartic acid), polar amino acids (glutamine and asparagine), hydrophobic amino acids (leucine, isoleucine, valine and methionine) Tryptophan and tyrosine), and small amino acids (glycine, alanine, serine and threonine).
  • basic amino acids arginine, lysine and histidine
  • acidic amino acids glutaminoe
  • polar amino acids glutaminoe
  • hydrophobic amino acids leucine, isoleucine, valine and methionine
  • Tryptophan and tyrosine Tryptophan and tyrosine
  • small amino acids glycine, alanine, serine and threonine.
  • amino acid substitutions that do not alter specific activity are known in the art.
  • Substantial variations in the biological properties of the peptide include (a) the structure of the polypeptide backbone within the substitution region, e.g., their effect in maintaining the sheet or helical conformation, (b) the charge of the molecule at the target site Or their effect in maintaining hydrophobicity, or (c) their effect in maintaining the bulk of the side chain is significantly different.
  • the natural residues are grouped into the following groups based on their usual side chain properties:
  • hydrophobicity norleucine, met, ala, val, leu, ile
  • Aromatic trp, tyr, phe.
  • Non-conservative substitutions will be made by exchanging one member of these members for another. Any cysteine residue not associated with maintaining the proper stereostructure of the peptide can generally be replaced with a serine to enhance the oxidative stability of the molecule and prevent strange cross-linking. Conversely, cysteine bond (s) can be added to the peptide to improve its stability
  • amino acid variants of peptides are those in which the glycosylation pattern of the antibody is altered.
  • the term change refers to the deletion of one or more carbohydrate moieties found in the peptide and / or the addition of one or more glycosylation sites that are not present in the peptide.
  • N-linked refers to a carbohydrate moiety attached to the side chain of an asparagine moiety.
  • the tripeptide sequences asparagine-X-serine and asparagine-X-threonine are recognition sequences for enzymatically attaching carbohydrate moieties to asparagine side chains.
  • O-linked glycosylation refers to attaching one of the sugars N-acetylgalactosamine, galactose or xylose to a hydroxyamino acid, most commonly serine or threonine, but 5-hydroxyproline or 5-hydroxylysine May be used.
  • Addition of the glycosylation site to the peptide is conveniently accomplished by varying the amino acid sequence to contain one or more of the above-mentioned tripeptide sequences (in the case of N-linked glycosylation sites). Such changes may be made by adding one or more serine or threonine residues to the sequence of the original antibody or by substituting these residues (for O-linked glycosylation sites).
  • the peptide of SEQ ID NO: 1 according to one aspect of the present invention has an advantage of low intracellular toxicity and high in vivo stability.
  • a pharmaceutical composition comprising at least one peptide comprising the amino acid sequence of SEQ ID NO: 1 or a peptide thereof as an active ingredient.
  • the pharmaceutical composition for prevention and treatment of inflammation, fibrosis, wound, and cancer-related diseases comprises 0.01 mg / mL to 0.1 mg / mL, 1 mg of the peptide comprising SEQ ID NO: / mL, 10 mg / mL, and 100 mg / mL.
  • the difference in the effect depending on the dose is shown, it can be appropriately controlled.
  • it is contained in the above-mentioned range or below, it is not only suitable for exhibiting the intended effect of the present invention but also can satisfy both the stability and safety of the composition and may be suitably included in the above range in terms of cost effectiveness .
  • composition according to one aspect of the present invention can be applied to all animals including humans, dogs, chickens, pigs, cattle, sheep, guinea pigs or monkeys.
  • composition according to one aspect of the present invention can be administered orally, rectally, transdermally, intravenously, intramuscularly, intraperitoneally, intramuscularly, intradermally or subcutaneously.
  • Formulations for oral administration may be, but are not limited to, tablets, pills, soft or hard capsules, granules, powders, solutions or emulsions.
  • Formulations for parenteral administration may be, but are not limited to, injections, drops, lozenges, ointments, gels, creams, suspensions, emulsions, suppositories, patches or spraying agents.
  • the pharmaceutical composition according to one aspect of the present invention may contain additives such as a diluent, an excipient, a lubricant, a binder, a disintegrant, a buffer, a dispersant, a surfactant, a colorant, a fragrance or a sweetener as necessary.
  • additives such as a diluent, an excipient, a lubricant, a binder, a disintegrant, a buffer, a dispersant, a surfactant, a colorant, a fragrance or a sweetener as necessary.
  • the pharmaceutical composition according to one aspect of the present invention can be prepared by a conventional method in the art.
  • the effective ingredients of the pharmaceutical composition according to one aspect of the present invention will vary depending on the age, sex, weight, pathological condition and severity of the subject to be administered, route of administration, or judgment of the prescriber. Determination of the amount of application based on these factors is within the level of ordinary skill in the art and its daily dose is, for example, from 0.1 to 100 g / kg / day, for example from 10 to 10 g / kg Kg / day, more specifically from 100 ⁇ g / kg / day to 1 g / kg / day, more specifically from 500 ⁇ g / kg / day to 100 mg / kg / day, It can be adjusted appropriately.
  • the pharmaceutical composition according to one aspect of the present invention may be administered once to three times a day, but is not limited thereto.
  • the formulation of the composition according to one aspect of the present invention is not particularly limited, but may be formulated into, for example, tablets, granules, powders, liquids, solid preparations and the like. Each formulation may be blended without difficulty by a person skilled in the art according to the purpose of formulation or use, in addition to the active ingredient, and the synergistic effect may occur when the composition is applied simultaneously with other ingredients.
  • a composition comprising a peptide according to one aspect of the present invention is useful for the treatment of inflammatory bowel disease such as rheumatoid arthritis, psoriasis, psoriatic arthritis, atopic dermatitis, ulcerative colitis and Crohn's disease, ankylosing spondylitis, multiple sclerosis, systemic lupus erythematosus (SLE) Related diseases selected from the group consisting of chronic obstructive pulmonary disease (COPD), sepsis, endotoxic shock, hepatitis and type 1 diabetes mellitus.
  • COPD chronic obstructive pulmonary disease
  • COPD chronic obstructive pulmonary disease
  • sepsis sepsis
  • endotoxic shock hepatitis
  • type 1 diabetes mellitus type 1 diabetes mellitus.
  • composition comprising a peptide according to one aspect of the present invention can be used as a pharmaceutical composition for preventing and treating fibrosis induced by selecting one or more members selected from the group consisting of cancer, administration of an anti-cancer agent, and exposure to radiation.
  • a pharmaceutical composition for the prevention and treatment of fibrosis comprising peptides according to one aspect of the present invention is a composition for preventing and treating fibrosis of a cancer cell tissue selected from the group consisting of pancreatic cancer, colon cancer, stomach cancer, prostate cancer, non-small cell lung cancer, breast cancer, melanoma and ovarian cancer It can exhibit an effect of suppressing fibrosis.
  • a composition comprising a peptide according to one aspect of the present invention is useful for preventing or treating skin diseases or worsening selected from the group consisting of skin wrinkles, skin wrinkles, skin exudates, epidermal burns, epidermal lacerations, epidermal wounds and combinations thereof And can be used as a pharmaceutical composition.
  • An aspect of the present invention provides a cosmetic composition comprising the peptide or a salt thereof.
  • the cosmetic composition contains a cosmetically or dermatologically acceptable medium or base. It may be any formulation suitable for topical application, for example, a solution, a gel, a solid, an anhydrous product of a paste, an emulsion obtained by dispersing an oil phase in an aqueous phase, an emulsion obtained by dispersing a water phase in an oil phase, a multi-emulsion, May be used in the form of an aerosol or patch further comprising a capsule, a microgranule, an ionic (liposome) and a non-ionic follicle dispersant, a foam, a compressed propellant.
  • These compositions may be prepared according to conventional methods in the art.
  • the above-mentioned cosmetic composition may contain other ingredients that can give a synergistic effect to the main effect within a range not impairing the main effect, and other ingredients other than the active ingredient of the present invention may be added to other cosmetic Depending on the formulation of the composition or the purpose of use, a person skilled in the art can mix and choose without difficulty.
  • the cosmetic composition of the present invention may contain, in addition to the above-mentioned active ingredients, other components which are usually formulated in cosmetic compositions as required, and examples thereof include a moisturizing agent, an emollient agent, a surfactant, Antioxidants, stabilizers, thickeners, glycerin, pH adjusters, alcohols, pigments, flavorings, blood circulation accelerators, coolants, antiperspirants and purified water.
  • the other ingredients to be contained in the cosmetic composition are not limited thereto, and the amount of the ingredients may be within the range that does not impair the objects and effects of the present invention.
  • the formulation of the cosmetic composition is not particularly limited and may be appropriately selected according to the purpose.
  • a soap preparation a flexible lotion, a nutritional lotion, an essence, a nutritional cream, a massage cream, a pack, a gel, a makeup base, a foundation, a powder, a lipstick, a patch, Hair cleansing water, cleanser, hair shampoo, hair conditioning, hair treatment, hair essence, hair lotion, scalp hair tonic, scalp essence, hair gel, hair spray, hair pack, body lotion, body cream, body oil and body essence , ≪ / RTI > but are not limited thereto.
  • the formulation of the food composition according to the present specification is not particularly limited, but may be formulated into, for example, tablets, granules, powders, liquid preparations such as a drink, caramels, gels, bars and the like.
  • the food composition of each formulation can be blended with the ingredients commonly used in the field in addition to the active ingredient without difficulty by those skilled in the art depending on the purpose of formulation or use, and synergistic effect can be obtained when the composition is applied simultaneously with other ingredients.
  • the dosage determination of the active ingredient is within the level of those skilled in the art, and its daily dosage is, for example, from 0.1 mg / kg / day to 5000 mg / kg / day, mg / kg / day to 500 mg / kg / day, but it is not limited thereto, and may vary depending on various factors such as the age, health condition, and complication of the subject.
  • the food composition according to the present invention may be used as a food or beverage such as various foods such as chewing gum, caramel product, candy, ice cream, confectionery, beverage such as soft drink, mineral water, alcoholic beverage, healthful food including vitamins and minerals .
  • the food composition which is one aspect of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and enhancers (cheese, chocolate etc.), pectic acid and its salts, Alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like.
  • the functional food compositions of the present invention may comprise natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally included in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
  • Preferred embodiments of the present invention include the most optimal mode known to the inventors for carrying out the present invention. Variations of the preferred embodiments may become apparent to those skilled in the art upon reading the foregoing description. The inventors expect those skilled in the art to appropriately utilize such variations, and the inventors expect the invention to be practiced otherwise than as described herein. Accordingly, the present invention includes equivalents and all modifications of the subject matter of the invention as recited in the appended claims, as permitted by the patent law. Moreover, any combination of the above-mentioned components within all possible variations is included in the present invention unless otherwise specified or contradicted by context. While the present invention has been particularly shown and described with reference to exemplary embodiments, those skilled in the art will readily appreciate that various changes in form and detail may be made without departing from the spirit and scope of the invention as defined by the following claims.
  • the novel peptide of SEQ ID NO: 1 was prepared according to a conventional solid phase peptide synthesis method. Specifically, the peptides were synthesized by coupling one amino acid from the C-terminal through Fmoc solid phase peptide synthesis (SPPS) using ASP48S (Peptron, Inc., Daejeon, Korea). The first amino acid at the C-terminus of the peptides attached to the resin was used as follows. For example:
  • Boc, t-Bu (t-butylester), Pbf (2, 2, 4, 6, 6), which are all amino acid sources used for peptide synthesis, are protected by N-term and Fmoc, 7-pentamethyl dihydro-benzofuran-5-sulfonyl).
  • HBTU 2- (1H-Benzotriazole-1-yl) -1,1,3,3-tetramethylaminium hexafluorophosphate
  • HOBt N-Hydroxxybenzotriazole
  • NMM NMM
  • Each of the peptides was synthesized by repeating the steps of reacting corresponding amino acids with a starting amino acid having an amino acid protecting group bonded thereto on a solid support, washing with a solvent, followed by deprotection.
  • the synthesized peptide was cleaved from the resin and purified by HPLC. The success of the synthesis was confirmed by LC / MS and lyophilized.
  • ALTSKLRA SEQ ID NO: 2
  • TNF- ⁇ which is known as cytokine exhibiting inflammatory activity in the inflammatory cell line induced by LPS (Lipopolysaccharide)
  • LPS Lipopolysaccharide
  • THP-1 human acute monocytic leukemia cell line
  • ATCC American Type Culture Collection
  • VA Manassas, VA, USA
  • the THP-1 was a 96-well plate so that the 1 X 10 5 cells per well suspended in RPMI 1640 medium and incubated for 24 hours.
  • PMA phorbol 12-myristate 13-acetate, Sigma
  • Lipopolysaccharide (LPS, Sigma) was dissolved in PBS (phosphate buffered saline) and PMA was dissolved in DMSO (dimethyl sulfoxide).
  • the peptides were synthesized in Peptron (Daejeon, Republic of Korea) according to the synthetic method in Example 1 and used.
  • the RT-qPCR test method was as follows. THP-1 cells were plated in 6-well plates at 2 ⁇ 10 6 / well and treated with 100 ng / ml PMA for 24 hours to differentiate into Macrophages. After removing the media, the differentiated THP-1 cells were washed twice with SFM (serum-free media), and then incubated with 10 ng / ml LPS and 1, 5 and 10 ⁇ M concentration of the novel peptide SEQ ID NO: 1 (ALTSKLRG) SEQ ID NO: 2 (ALTSKLRA), which is a control peptide, was treated and cultured for 6 hours.
  • SFM serum-free media
  • the PCR conditions were 40 cycles (95 to 15 seconds, 55 to 30 seconds, 72 to 30 seconds) and the sequences of the primers used were as shown in Table 3 below
  • the ELISA test method was as follows. THP-1, a monocyte cell line distributed from ATCC, is subcultured and prepared in the P3 stage. The cell line is divided into well-plates and treated with PMA to differentiate into macrophages. The differentiated cells were treated with LPS to induce an inflammatory response (induced TNF-alpha production), and the cells were seeded with the novel peptide SEQ ID NO: 1 (ALTSKLRG) and positive control peptide SEQ ID NO: 2 (ALTSKLRA) 0.05, 0.5, 5 [mu] M) to measure the amount of TNF- [alpha] by ELISA.
  • THP-1 a monocyte cell line distributed from ATCC
  • the cell line is divided into well-plates and treated with PMA to differentiate into macrophages.
  • the differentiated cells were treated with LPS to induce an inflammatory response (induced TNF-alpha production), and the cells were seeded with the novel peptide SEQ ID NO: 1 (ALTSKLRG) and positive control peptide
  • E2 is known to be a steroid that inhibits the production of TNF- ⁇ in THP-1.
  • TNF- ⁇ mRNA The expression levels of TNF- ⁇ mRNA were measured by RT-qPCR, and compared with the LPS-induced inflammatory response of LPS in THP-1 cells, the expression of each peptide
  • SEQ ID NO: 1 the novel peptide, SEQ ID NO: 1 (ALTSKLRG) showed excellent inhibitory effect on TNF- ⁇ gene expression at all concentrations.
  • 1 uM and 5 uM showed positive control peptides (SEQ ID NO: 2) (ALTSKLRA).
  • SEQ ID NO: 2 the anti-inflammatory activity was much superior to that of the positive control peptide, SEQ ID NO: 2 (see FIG.
  • the anti-inflammatory activity of the novel peptides was confirmed by ELISA as inhibitory effect on TNF- ⁇ production of THP-1 cells.
  • the peptide of SEQ ID NO: 1 showed TNF- ⁇ production inhibitory effect at all concentrations.
  • it showed excellent effects compared to positive control group E2 and SEQ ID NO: 2 (ALTSKLRA) (see FIG. 2).
  • the novel peptide according to the present invention exhibits an anti-inflammatory activity exhibiting inhibition of TNF- ?.
  • Experiments on the inhibition of TNF- ⁇ are known to be the most basic experiments for proving the total inflammation inhibitory effect, and it is understood that the novel peptide of the present invention has an overall anti-inflammatory effect.
  • the reagents and materials used for this experiment are as follows.
  • the new peptides in the powder state were dissolved in filtered 0.2 ⁇ m filtered sterile water into a 0.2 ⁇ m filter, aliquoted at -70 ° C., and used for dissolution.
  • the cell line used was HepG2 (ATCC HB-8065; American Type Culture Collection), and recombinant human TGF- ⁇ was dissolved in 4 mM HCl to prepare 10 ⁇ g / mL stock.
  • the novel peptide SEQ ID NO: 1 (ALTSKLRG) and the positive control peptide SEQ ID NO: 2 (ALTSKLRA) were prepared according to Example 1 above.
  • SB431542 (Sigma) used as a positive control was prepared to be 10 mM stock.
  • HepG2 cells (ATCC HB-8065;) are seeded in a 60 mm petri dish and cultured in a CO 2 incubator for 16 hours. The medium is then replaced with SFM (serum-free medium) and cultured for an additional 24 hours. The medium is then exchanged with TGF- beta 1 at a concentration of 10 ng / ml and the peptides are further treated with concentration (1, 10 [mu] M) for 72 hours. Each peptide-treated group is further incubated in a CO 2 incubator at 37 ° C for 1 hour.
  • the peptide-treated cells were washed twice with PBS, collected in a 1.5 mL EP tube with a cell scraper, and the supernatant was removed with a centrifuge (1,000 rpm, 4 ° C, 2 minutes) Add 100 ⁇ L each. Incubate for 40 min on ice, shake for 10 min (vortex, micro-centrifuge pre-cooled to 4 ° C) and mix samples 40-50 times using 1 ml syringe. Finally, the supernatant is centrifuged at 13,000 rpm for 15 minutes.
  • PVDF membrane polyvinylidene difluoride membranes, Millipore
  • SDS-PAGE sodium dodecyl sulfate-polyacrylamide gel electrophoresis
  • the PVDF membrane is blocked with 5% skim milk and incubated with primary antibodies.
  • the antibodies used in this experiment are as follows. Smad 2/3 (60, 52 kDa, 5% BSA 1: 1000, # 3102, Cell signaling), pSmad2 / 3 (cell signaling # 3102), GAPDH (37 kDa, signaling).
  • the PVDF membrane is then washed with TBST (Tris-buffered saline containing 0.1% Tween-20) and reacted with HRP-conjugated anti-rabbit antibody (Jackson Immuno Research Laboratories, INC.). Thereafter, ECL detection (detection, Amersham Pharmacia Biotech) was performed and the obtained image was analyzed with an image analyzer (GE Healthcare, ImageQuant LAS 4000).
  • TBST Tris-buffered saline containing 0.1% Tween-20
  • HRP-conjugated anti-rabbit antibody Jackson Immuno Research Laboratories, INC.
  • TGF- ⁇ inhibition pSmad2 / 3 Smad2 / 3 was used as TGF- ⁇ signaling activity markers and GAPDH was used as a reference group for electrophoresis.
  • the TGF-beta signal transduction activity markers were those expressed at higher concentrations as TGF-beta was inhibited.
  • the novel peptide according to the present invention exhibits an anti-fibrosis activity exhibited by inhibition of TGF- ⁇ .
  • Experiments on the inhibition of TGF- [beta] are known to be widely used in experiments for anti-fibrosis activity.
  • the novel peptides of the present invention have an anti-fibrosis activity effect.
  • SD rats Male-Dawley Rats
  • the male was selected to exclude the effect of hormone change.
  • the male was 6 weeks old and was acclimated for about 1 week. However, to elaborate the experimental results, the experiment was performed until 11 weeks old. The animals were sensitized to the olfactory senses and could injure other animals. Therefore, each animal was separated from the wounds after they were wounded.
  • the animals were divided into the following groups and the drug was applied immediately after wounding and at intervals of two days.
  • the substance was used at a concentration of 1 mg / ml and diluted 10 times with 100 ⁇ g / ml immediately before the experiment.
  • the application was carried out at a dose of 50 ⁇ l per wound.
  • Control group 50 ⁇ l of physiological saline solution per wound
  • Biopsies for collagen formation were performed on both the third and fifth day after wounding, by collecting both wounded parts of the back of each of two control specimens and two experimental specimens. To compare collagen synthesis, average fluorescence intensity was measured after masson trichrome staining.
  • the wound size was smaller than that of the control group on the first day after induction of the full thickness wound (see FIG. 4).
  • the difference in size of the wounds was observed at the 11th day of the healing period.
  • the fact that wounds were reduced in the experimental group compared to the control group at the initial stage after wounding was considered as evidence that the new peptide was effective at the early stage of wounding .
  • the novel peptide according to the present invention has an activity of reducing the wound area and increasing collagen synthesis.
  • the novel peptide of the present invention can have a wound healing activity effect.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)

Abstract

La présente invention concerne un nouveau peptide et une composition le comprenant et, plus particulièrement, l'invention concerne un nouveau peptide présentant une efficacité prophylactique et thérapeutique anti-inflammatoire, contre la fibrose, de cicatrisation des plaies et anticancéreuse, ainsi qu'une composition le comprenant. Le nouveau peptide et la composition le comprenant, fournis par la présente invention, présentent un effet de soulagement, de prévention et de traitement de symptômes tels que l'inflammation, la fibrose, les plaies et des maladies telles que le cancer, y compris les symptômes, et peut ainsi fournir une méthode prophylactique et thérapeutique pour des maladies associées.
PCT/KR2017/013532 2017-11-24 2017-11-24 Nouveau peptide et composition le comprenant Ceased WO2019103203A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
KR1020207010376A KR102436084B1 (ko) 2017-11-24 2017-11-24 신규 펩티드 및 이를 포함한 조성물
PCT/KR2017/013532 WO2019103203A1 (fr) 2017-11-24 2017-11-24 Nouveau peptide et composition le comprenant

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/KR2017/013532 WO2019103203A1 (fr) 2017-11-24 2017-11-24 Nouveau peptide et composition le comprenant

Publications (1)

Publication Number Publication Date
WO2019103203A1 true WO2019103203A1 (fr) 2019-05-31

Family

ID=66631549

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2017/013532 Ceased WO2019103203A1 (fr) 2017-11-24 2017-11-24 Nouveau peptide et composition le comprenant

Country Status (2)

Country Link
KR (1) KR102436084B1 (fr)
WO (1) WO2019103203A1 (fr)

Cited By (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020263830A1 (fr) 2019-06-25 2020-12-30 Gilead Sciences, Inc. Protéines de fusion flt3l-fc et procédés d'utilisation
WO2021072724A1 (fr) * 2019-10-18 2021-04-22 沛尔生技医药股份有限公司 Peptide et son utilisation dans la préparation d'un médicament pour le traitement de maladies inflammatoires et de la douleur
WO2021087064A1 (fr) 2019-10-31 2021-05-06 Forty Seven, Inc. Traitement d'un cancer du sang basé sur une thérapie anti-cd47 et anti-cd20
WO2021096860A1 (fr) 2019-11-12 2021-05-20 Gilead Sciences, Inc. Inhibiteurs de mcl1
WO2021130638A1 (fr) 2019-12-24 2021-07-01 Carna Biosciences, Inc. Composés modulant la diacylglycérol kinase
WO2021163064A2 (fr) 2020-02-14 2021-08-19 Jounce Therapeutics, Inc. Anticorps et protéines de fusion se liant à ccr8, et leurs utilisations
WO2021222522A1 (fr) 2020-05-01 2021-11-04 Gilead Sciences, Inc. Composés de 2,4-dioxopyrimidine inhibant cd73
WO2022221304A1 (fr) 2021-04-14 2022-10-20 Gilead Sciences, Inc. CO-INHIBITION DE LA LIAISON CD47/SIRPα ET DE LA SOUS-UNITÉ RÉGULATRICE DE L'ENZYME E1 ACTIVANT NEDD8 POUR LE TRAITEMENT DU CANCER
WO2022245671A1 (fr) 2021-05-18 2022-11-24 Gilead Sciences, Inc. Méthodes d'utilisation de protéines de fusion flt3l-fc
WO2022271650A1 (fr) 2021-06-23 2022-12-29 Gilead Sciences, Inc. Composés de modulation de la diacylglycérol kinase
WO2022271684A1 (fr) 2021-06-23 2022-12-29 Gilead Sciences, Inc. Composés modulant les diacylglycérol kinases
WO2022271677A1 (fr) 2021-06-23 2022-12-29 Gilead Sciences, Inc. Composés de modulation de la diacylglycérol kinase
WO2022271659A1 (fr) 2021-06-23 2022-12-29 Gilead Sciences, Inc. Composés modulant les diacylglycérol kinases
WO2023077030A1 (fr) 2021-10-29 2023-05-04 Gilead Sciences, Inc. Composés cd73
WO2023076983A1 (fr) 2021-10-28 2023-05-04 Gilead Sciences, Inc. Dérivés de pyridine-3(2h)-one
WO2023122615A1 (fr) 2021-12-22 2023-06-29 Gilead Sciences, Inc. Agents de dégradation des doigts de zinc de la famille ikaros et leurs utilisations
WO2023122581A2 (fr) 2021-12-22 2023-06-29 Gilead Sciences, Inc. Agents de dégradation de doigt de zinc de la famille ikaros et utilisations associées
WO2023147418A1 (fr) 2022-01-28 2023-08-03 Gilead Sciences, Inc. Inhibiteurs de parp7
EP4245756A1 (fr) 2022-03-17 2023-09-20 Gilead Sciences, Inc. Agents de dégradation de la famille des doigts de zinc de l'ikaros et leurs utilisations
WO2023183817A1 (fr) 2022-03-24 2023-09-28 Gilead Sciences, Inc. Polythérapie pour le traitement de cancers exprimant trop -2
WO2023196784A1 (fr) 2022-04-05 2023-10-12 Gilead Sciences, Inc. Combinaisons de thérapies par anticorps pour traiter le cancer colorectal
WO2023205719A1 (fr) 2022-04-21 2023-10-26 Gilead Sciences, Inc. Composés modulateurs de kras g12d
WO2024006929A1 (fr) 2022-07-01 2024-01-04 Gilead Sciences, Inc. Composés cd73
WO2024064668A1 (fr) 2022-09-21 2024-03-28 Gilead Sciences, Inc. POLYTHÉRAPIE ANTICANCÉREUSE PAR RAYONNEMENT IONISANT FOCAL ET PERTURBATION CD47/SIRPα
EP4349413A2 (fr) 2019-10-18 2024-04-10 Forty Seven, Inc. Polythérapies pour le traitement de syndromes myélodysplasiques et de leucémie myéloïde aiguë
WO2024137852A1 (fr) 2022-12-22 2024-06-27 Gilead Sciences, Inc. Inhibiteurs de prmt5 et leurs utilisations
WO2024215754A1 (fr) 2023-04-11 2024-10-17 Gilead Sciences, Inc. Composés modulateurs de kras
WO2024220917A1 (fr) 2023-04-21 2024-10-24 Gilead Sciences, Inc. Inhibiteurs de prmt5 et leurs utilisations
WO2025006720A1 (fr) 2023-06-30 2025-01-02 Gilead Sciences, Inc. Composés modulateurs de kras
WO2025024663A1 (fr) 2023-07-26 2025-01-30 Gilead Sciences, Inc. Inhibiteurs de parp7
WO2025024811A1 (fr) 2023-07-26 2025-01-30 Gilead Sciences, Inc. Inhibiteurs de parp7
WO2025054530A1 (fr) 2023-09-08 2025-03-13 Gilead Sciences, Inc. Dérivés polycycliques contenant une pyrimidine utilisés comme composés de modulation de kras g12d
WO2025054347A1 (fr) 2023-09-08 2025-03-13 Gilead Sciences, Inc. Composés de modulation de kras g12d
WO2025096589A1 (fr) 2023-11-03 2025-05-08 Gilead Sciences, Inc. Inhibiteurs de prmt5 et leurs utilisations
WO2025137640A1 (fr) 2023-12-22 2025-06-26 Gilead Sciences, Inc. Inhibiteurs azaspiro de wrn
WO2025245003A1 (fr) 2024-05-21 2025-11-27 Gilead Sciences, Inc. Inhibiteurs de prmt5 et leurs utilisations

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20100061677A (ko) * 2007-09-11 2010-06-08 몬도바이오테크 래보래토리즈 아게 치료제로서의 ｔｙｒ-ｗ-ｍｉｆ-1 및 유로코르틴 2의 용도
WO2017116138A1 (fr) * 2015-12-28 2017-07-06 주식회사 젬백스앤카엘 Peptide inhibiteur de la mélanine et composition le contenant

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20100061677A (ko) * 2007-09-11 2010-06-08 몬도바이오테크 래보래토리즈 아게 치료제로서의 ｔｙｒ-ｗ-ｍｉｆ-1 및 유로코르틴 2의 용도
WO2017116138A1 (fr) * 2015-12-28 2017-07-06 주식회사 젬백스앤카엘 Peptide inhibiteur de la mélanine et composition le contenant

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DATABASE Protein 2 November 2016 (2016-11-02), "MarR family transcriptional regulator [Microbacterium testaceum", XP055618782, retrieved from NCBI Database accession no. WP_058623598.1 *
DATABASE Protein 22 December 2015 (2015-12-22), "transcriptional regulator [Microbacterium testaceum", XP055618786, retrieved from NCBI Database accession no. KTR94653.1 *
TRAVIS, TARYN E.: "A multimodal assessment of melanin and melanocyte activity in abnormally pigmented hypertrophic scar", JOURNAL OF BURN CARE & RESEARCH, 2015, pages 77 - 86, XP055618791 *

Cited By (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020263830A1 (fr) 2019-06-25 2020-12-30 Gilead Sciences, Inc. Protéines de fusion flt3l-fc et procédés d'utilisation
EP4349413A2 (fr) 2019-10-18 2024-04-10 Forty Seven, Inc. Polythérapies pour le traitement de syndromes myélodysplasiques et de leucémie myéloïde aiguë
WO2021072724A1 (fr) * 2019-10-18 2021-04-22 沛尔生技医药股份有限公司 Peptide et son utilisation dans la préparation d'un médicament pour le traitement de maladies inflammatoires et de la douleur
WO2021087064A1 (fr) 2019-10-31 2021-05-06 Forty Seven, Inc. Traitement d'un cancer du sang basé sur une thérapie anti-cd47 et anti-cd20
WO2021096860A1 (fr) 2019-11-12 2021-05-20 Gilead Sciences, Inc. Inhibiteurs de mcl1
EP4445902A2 (fr) 2019-12-24 2024-10-16 Carna Biosciences, Inc. Composés modulant la diacylglycérol kinase
WO2021130638A1 (fr) 2019-12-24 2021-07-01 Carna Biosciences, Inc. Composés modulant la diacylglycérol kinase
US11692038B2 (en) 2020-02-14 2023-07-04 Gilead Sciences, Inc. Antibodies that bind chemokine (C-C motif) receptor 8 (CCR8)
WO2021163064A2 (fr) 2020-02-14 2021-08-19 Jounce Therapeutics, Inc. Anticorps et protéines de fusion se liant à ccr8, et leurs utilisations
US12297282B2 (en) 2020-02-14 2025-05-13 Gilead Sciences, Inc. Nucleic acids encoding, and methods of producing, antibodies that bind human chemokine (C—C motif) receptor 8 (CCR8)
WO2021222522A1 (fr) 2020-05-01 2021-11-04 Gilead Sciences, Inc. Composés de 2,4-dioxopyrimidine inhibant cd73
WO2022221304A1 (fr) 2021-04-14 2022-10-20 Gilead Sciences, Inc. CO-INHIBITION DE LA LIAISON CD47/SIRPα ET DE LA SOUS-UNITÉ RÉGULATRICE DE L'ENZYME E1 ACTIVANT NEDD8 POUR LE TRAITEMENT DU CANCER
WO2022245671A1 (fr) 2021-05-18 2022-11-24 Gilead Sciences, Inc. Méthodes d'utilisation de protéines de fusion flt3l-fc
WO2022271684A1 (fr) 2021-06-23 2022-12-29 Gilead Sciences, Inc. Composés modulant les diacylglycérol kinases
WO2022271659A1 (fr) 2021-06-23 2022-12-29 Gilead Sciences, Inc. Composés modulant les diacylglycérol kinases
WO2022271677A1 (fr) 2021-06-23 2022-12-29 Gilead Sciences, Inc. Composés de modulation de la diacylglycérol kinase
WO2022271650A1 (fr) 2021-06-23 2022-12-29 Gilead Sciences, Inc. Composés de modulation de la diacylglycérol kinase
WO2023076983A1 (fr) 2021-10-28 2023-05-04 Gilead Sciences, Inc. Dérivés de pyridine-3(2h)-one
WO2023077030A1 (fr) 2021-10-29 2023-05-04 Gilead Sciences, Inc. Composés cd73
WO2023122615A1 (fr) 2021-12-22 2023-06-29 Gilead Sciences, Inc. Agents de dégradation des doigts de zinc de la famille ikaros et leurs utilisations
WO2023122581A2 (fr) 2021-12-22 2023-06-29 Gilead Sciences, Inc. Agents de dégradation de doigt de zinc de la famille ikaros et utilisations associées
WO2023147418A1 (fr) 2022-01-28 2023-08-03 Gilead Sciences, Inc. Inhibiteurs de parp7
WO2023178181A1 (fr) 2022-03-17 2023-09-21 Gilead Sciences, Inc. Agents de dégradation des doigts de zinc de la famille ikaros et leurs utilisations
EP4464703A2 (fr) 2022-03-17 2024-11-20 Gilead Sciences, Inc. Agents de dégradation de la famille des doigts de zinc de l'ikaros et leurs utilisations
EP4245756A1 (fr) 2022-03-17 2023-09-20 Gilead Sciences, Inc. Agents de dégradation de la famille des doigts de zinc de l'ikaros et leurs utilisations
WO2023183817A1 (fr) 2022-03-24 2023-09-28 Gilead Sciences, Inc. Polythérapie pour le traitement de cancers exprimant trop -2
WO2023196784A1 (fr) 2022-04-05 2023-10-12 Gilead Sciences, Inc. Combinaisons de thérapies par anticorps pour traiter le cancer colorectal
WO2023205719A1 (fr) 2022-04-21 2023-10-26 Gilead Sciences, Inc. Composés modulateurs de kras g12d
WO2024006929A1 (fr) 2022-07-01 2024-01-04 Gilead Sciences, Inc. Composés cd73
WO2024064668A1 (fr) 2022-09-21 2024-03-28 Gilead Sciences, Inc. POLYTHÉRAPIE ANTICANCÉREUSE PAR RAYONNEMENT IONISANT FOCAL ET PERTURBATION CD47/SIRPα
WO2024137852A1 (fr) 2022-12-22 2024-06-27 Gilead Sciences, Inc. Inhibiteurs de prmt5 et leurs utilisations
WO2024215754A1 (fr) 2023-04-11 2024-10-17 Gilead Sciences, Inc. Composés modulateurs de kras
WO2024220917A1 (fr) 2023-04-21 2024-10-24 Gilead Sciences, Inc. Inhibiteurs de prmt5 et leurs utilisations
WO2025006720A1 (fr) 2023-06-30 2025-01-02 Gilead Sciences, Inc. Composés modulateurs de kras
WO2025024663A1 (fr) 2023-07-26 2025-01-30 Gilead Sciences, Inc. Inhibiteurs de parp7
WO2025024811A1 (fr) 2023-07-26 2025-01-30 Gilead Sciences, Inc. Inhibiteurs de parp7
WO2025054530A1 (fr) 2023-09-08 2025-03-13 Gilead Sciences, Inc. Dérivés polycycliques contenant une pyrimidine utilisés comme composés de modulation de kras g12d
WO2025054347A1 (fr) 2023-09-08 2025-03-13 Gilead Sciences, Inc. Composés de modulation de kras g12d
WO2025096589A1 (fr) 2023-11-03 2025-05-08 Gilead Sciences, Inc. Inhibiteurs de prmt5 et leurs utilisations
WO2025137640A1 (fr) 2023-12-22 2025-06-26 Gilead Sciences, Inc. Inhibiteurs azaspiro de wrn
WO2025245003A1 (fr) 2024-05-21 2025-11-27 Gilead Sciences, Inc. Inhibiteurs de prmt5 et leurs utilisations

Also Published As

Publication number Publication date
KR102436084B1 (ko) 2022-08-25
KR20200044969A (ko) 2020-04-29

Similar Documents

Publication Publication Date Title
WO2019103203A1 (fr) Nouveau peptide et composition le comprenant
WO2016190660A1 (fr) Nouveau peptide et composition le contenant
EP3061459B1 (fr) Composition de traitement et de prévention de l'hypertrophie bénigne de la prostate
WO2013169060A1 (fr) Composition pour la prévention ou le traitement d'une sepsie
WO2015156649A1 (fr) Peptide présentant une activité inhibitrice contre la fibrose, et composition le contenant
WO2022050634A1 (fr) Peptide, composition cosmétique et composition pharmaceutique le comprenant
WO2015093854A1 (fr) Composition pour traiter un cancer de la prostate
WO2017155232A2 (fr) Peptide présentant une activité favorisant la croissance des cheveux et/ou une activité favorisant la production de mélanine et son utilisation
WO2019045248A2 (fr) Peptide présentant une activité d'atténuation des rides et utilisations associées
KR102077983B1 (ko) 피부 주름 개선 및 미백용 조성물
WO2013137569A1 (fr) Tétrapeptide, et composition cosmétique contre le vieillissement et l'inflammation de la peau qui en comprend
WO2021251790A1 (fr) Conjugué acide désoxycholique-peptide à activité anti-obésité et son utilisation
KR102093093B1 (ko) 피부 노화 개선용 조성물
KR20180089440A (ko) 멜라닌 억제 기능성 펩티드 및 이를 포함하는 조성물
WO2018034453A1 (fr) Conjugué de minoxidil et d'un peptide
WO2017119756A1 (fr) Nouveau peptide fonctionnel anti-inflammatoire, blanchissant la peau, anti-âge et atténuant les rides, et composition contenant le peptide
WO2019231175A1 (fr) Peptide à terminaison carboxy amidée ayant une activité inhibitrice de la mélanogenèse et composition le comprenant
WO2024122713A1 (fr) Peptide présentant une activité d'amélioration de l'état de la peau et son utilisation
WO2025037902A1 (fr) Nouveau peptide ayant une activité d'amélioration de l'état de la peau et ses utilisations
WO2025023694A1 (fr) Composition pour améliorer l'état de la peau comprenant un complexe peptidique en tant que principe actif
WO2017111388A1 (fr) Composition comprenant un peptide dérivé de périostine en tant que substance active pour stimuler l'angiogenèse
WO2024122718A1 (fr) Peptide pour régénérer le cartilage et ses utilisations
WO2024106822A1 (fr) Peptide ayant une activité de blanchiment de la peau et son utilisation
WO2024122722A1 (fr) Peptide pour régénérer le cartilage et ses utilisations
WO2024106823A1 (fr) Peptide ayant une activité de blanchiment de la peau et son utilisation

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: 17932671

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 20207010376

Country of ref document: KR

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 17932671

Country of ref document: EP

Kind code of ref document: A1