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WO2007078034A1 - Composition pour inhiber des derives de benzimidazole amine contenant des proteines c-kit - Google Patents

Composition pour inhiber des derives de benzimidazole amine contenant des proteines c-kit Download PDF

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Publication number
WO2007078034A1
WO2007078034A1 PCT/KR2006/001988 KR2006001988W WO2007078034A1 WO 2007078034 A1 WO2007078034 A1 WO 2007078034A1 KR 2006001988 W KR2006001988 W KR 2006001988W WO 2007078034 A1 WO2007078034 A1 WO 2007078034A1
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WO
WIPO (PCT)
Prior art keywords
composition
kit protein
derivatives
inhibiting
kit
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/KR2006/001988
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English (en)
Inventor
Yong-Joo Na
Soo-Mi Ahn
Heung-Soo Baek
Hyun-Jung Shin
Jae-Sung Hwang
Ih-Seop Chang
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.)
Amorepacific Corp
Original Assignee
Amorepacific Corp
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 Amorepacific Corp filed Critical Amorepacific Corp
Publication of WO2007078034A1 publication Critical patent/WO2007078034A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4946—Imidazoles or their condensed derivatives, e.g. benzimidazoles

Definitions

  • the invention relates to a composition for inhibiting the c-kit protein or composition for the skin whitening containing at least one of benzimidazole amine derivatives and aminoquinoline derivatives, and more particularly to a composition of an external preparation formulation for skin containing the derivatives to inhibit the melanin synthesis and thus to ultimately accomplish the skin whitening effect, using the function of inhibiting the activity of the c-kit protein which is present on a surface of a melanocyte, in addition to the well-known functions of the compounds.
  • the c-kit is a cell surface protein belonging to a receptor tyrosine kinase type III family and is a receptor of a stem cell factor (SCF).
  • SCF stem cell factor
  • the c-kit protein undergoes the dimerization and has an activity of phosphorylating itself. It then undergoes the Ras-Raf-MAP kinase cascade in the intracellular signal transfer, and activates the Microphthalmia-Associated Transcription Factor (Mitf), thereby accelerating the tyrosinase synthesis and deriving the melanogenesis in the melanocyte.
  • Mitf Microphthalmia-Associated Transcription Factor
  • the SCF/c-kit signal transfer is also associated with the pigmentation that is derived by the ultraviolet B. It is thought that the mechanism thereof may be related to an increase of the SCF expression in the keratinocyte and an increase of the c-kit expression in the melanocyte. In fact, it can be seen that gene and protein expressions of the SCF and the c- kit are increased when the ultraviolet B stimulation is applied during the cell culture of the keratinocyte and melanocyte.
  • the inventors confirmed that the compounds such as benzimidazole amine derivatives, in particular l-(4-methoxyphenyl)-N-(l- naphthalenylmethyl)-lH-benzimidazole-5-amine (hereinafter, referred to as "SB-CK-111”), and aminoquinol ine derivatives, particularly 2-amino-3-(3,4- dimethoxyphenyO-quinoline (hereinafter, referred to as "SB-CK-141”) have an efficacy of inhibiting the c-kit protein activity.
  • benzimidazole amine derivatives in particular l-(4-methoxyphenyl)-N-(l- naphthalenylmethyl)-lH-benzimidazole-5-amine
  • aminoquinol ine derivatives particularly 2-amino-3-(3,4- dimethoxyphenyO-quinoline
  • an object of the invention is to provide a composition for inhibiting the c-kit protein or composition for the skin whitening containing such compounds as effective ingredients.
  • composition for inhibiting the c-kit protein containing at least one of the benzimidazole amine derivatives and the aminoquinol ine derivatives.
  • composition for the skin whitening containing at least one of the benzimidazole amine derivatives and the aminoquinol ine derivatives.
  • the benzimidazole amine derivative is l-(4- methoxyphenyl)-N-(l-naphthalenylmethyl)-lH-benzimidazole-5 ⁇ amine expressed by a following chemistry figure 1.
  • the aminoquinol ine derivative is 2-amino-3- (3,4-dimethoxyphenyl)-quinoline expressed by a following chemistry figure 2. [chemi stry f igure 2]
  • the composition inhibits an activity of the c-kit protein.
  • the composition for inhbiting the c-kit protein has a use of skin whitening.
  • At least one of the benzimidazole amine derivative and the aminoquinoline derivative inhibits a cell signaling in the melanocyte, in which the c-kit protein participates, thereby regulating a function of the melanocyte.
  • At least one of the benzimidazole amine derivative and the aminoquinol ine derivative is contained in an amount of 0.0001-10 wt% for a total weight of the composition.
  • the composition is a cosmetic composition or pharmaceutical composition.
  • the benzimidazole amine derivative SB-CK-I11 and the aminoquinol ine derivative SB-CK-141 have the effect of inhibiting the c-kit protein activity which is a cell surface protein of the melanocyte. Since it inhibits a cell signaling in the melanocyte, in which the c-kit protein participates, thereby regulating a function of the melanocyte and ultimately inhibiting the melanogenesis to exhibit the skin whitening effect, the composition for inhibiting the c-kit protein or composition for the skin whitening containing them can be usefully used as a cosmetic composition or pharmaceutical composition. [Description of Drawings]
  • FIG. 1 is a graph showing an inhibiting effect of SU11248 on the c-kit protein activity, which is dependent on the concentration
  • FIG. 2 is a graph showing an inhibiting effect of l-(4-methoxyphenyl)- N-(l-naphthalenylmethyl)-lH-benzimidazole-5-amine (hereinafter, referred to as "SB-CK-111”) and 2-amino-3-(3,4-dimethoxyphenyl)-quinoline (hereinafter, referred to as "SB-CK-141”) of the invention on the c-kit protein activity;
  • FIG. 3 is a photograph showing an induction of the c-kit protein activity (i.e. phosphorylation) by a stem cell factor (SCF) and an inhibition of the c-kit protein activity by SU11248 in a cell level;
  • SCF stem cell factor
  • FIG. 4 is a photograph showing an inhibiting effect of SB-CK-111 of the invention on the c-kit protein activity in a cell level.
  • FIG. 5 is a photograph showing an inhibiting effect of SB-CK-141 on the c-kit protein activity in a cell level. [Best Mode]
  • the benzimidazole amine derivatives and the aminoquinoline derivatives, having a skin whitening function, of the invention can be added to a composition of an external preparation formulation for skin, such as cosmetic composition or pharmaceutical composition.
  • the composition for inhibiting the c-kit protein or composition for the skin whitening according to the invention preferably contains at least one of the benzimidazole amine derivatives and the aminoquinoline derivatives in an amount of 0.0001-10 wt% for a total weight of the composition.
  • the content is less than 0.0001 wt%, the effects thereof cannot be expected, and when the content is more than 10 wt%, it can cause the safety or formulation stability problem. If the effective effects, the safety and the formulation stability are considered, the content is more preferably 0.01-1.0 wt%.
  • the cosmetic composition of the invention may further contain other ingredients preferably capable of providing a synergy effect to the main effect, within a range of not deteriorating the main effect of the invention, in addition to at least one of the benzimidazole amine derivatives and the aminoquinoline derivatives.
  • At least one of the benzimidazole amine derivatives and the aminoquino11ne derivatives of the invention is preferably prepared in a form of the cosmetic formulation and applied as it is However, they can be used as a typical external preparation
  • the cosmetic composition of the invention can be used in the cosmetics for inhibiting the c-kit protein or the skin whitening effect
  • the product to which the composition of the invention can be added includes, for example, the cosmetics such as various creams, lotions and the like, cleansing agent, washing agent, soap, cosmetic solution, etc
  • composition of the invention containing at least one of the benzimidazole amine derivatives and the aminoquinoline derivatives may take a form of solution, emulsion, viscous mixture
  • the cosmetics of the invention are not particularly limited with regard to the formulations thereof.
  • the formulations may include emulsion, cream, toilet water, essence, pack, gel, powder makeup base foundation, lotion, ointment, patch, cosmetic solution, cleansing foam, cleansing cream, cleansing water, body lotion, body cream, body oil, body essence, shampoo rinse, body cleansing agent, soap, hair-dye, spray and the like
  • the other ingredients except at the least of the benzimidazole amine derivatives and the aminoquinoline derivatives may be arbitrarily mixed by the one skilled in the art without any difficulty depending on the formulations or use of the cosmetic compositions
  • the above pharmaceutical preparation may contain a material of enhancing the absorption so as to improve the effect of inhibiting the c-kit protein and the skin whitening.
  • the cosmetics of the invention may contain any ingredient selected from a group consisting of water-soluble vitamin, oil-soluble vitamin, polymer peptide polymer polysaccharide, sphingolipid and seaweed extracts ⁇ 77>
  • the cosmetics of the invention may contain another ingredients, which are mixed in the typical cosmetics, as required, in addition to the essential ingredients,
  • the other ingredients which can be added may include oil and fat ingredient, moisturizing agent, emollient agent, surfactant, organic and inorganic pigments, organic powder, ultraviolet absorbent, antiseptic, fungicide, antioxidant, plant extract, pH adjuster, alcohol, colorant, flavour, blood circulation accelerant, frigidity agent, anhydrotics, purified water and the like.
  • ingredients that can be added are not limited to the above ingredients and any ingredient may be mixed within a range of not deteriorating the object and the effect of the invention.
  • the pharmaceutical composition of the invention may be administrated in oral, non-oral, rectal, local, percutaneous, intravenous, intramuscular, intraperitoneal, subcutaneous administrations.
  • the percutaneous administration is the most preferable.
  • the dosage of the active ingredient is different depending on ages, sexes and weights of the patient to be treated, specific diseases or pathological state to be treated, seriousness of the disease or pathological state, administration route, prescriber's decision and the like.
  • the dosage decision based on such factors is within a level of the one skilled in the art.
  • the dosage is about 0.001 mg/kg/day to 2000 mg/kg/day.
  • the preferred dosage is 0.5 mg/kg/day to 2,5 mg/kg/day.
  • 1.0 to 3.0 ml/day may be applied one to five times per day for one month or more.
  • the pharmaceutical composition may be administrated in a solid, semi-solid or liquid form depending on the intended administration types.
  • the administration types may include, but not limited to, tablet, pill, capsule, suppository, small bag, granule, powder, cream, lotion, ointment, gel, patch, spary, sticking plaster, liquid solution, suspensions, dispersions, emulsions, syrup and the like.
  • the active ingredient may be encapsulated in liposome, fine particles or microcapsules.
  • the most preferred formulation is the formulation for the percutaneous administration, such as cream, lotion, ointment, gel, patch, spray, liquid solution, suspensions, dispersions or emulsions.
  • the solid composition such as tablet, pill and granule may be conveniently coated.
  • the composition for the intravenous administration is the solution in sterilized isotonic aqueous buffer solution and includes the local anesthetic so as to alleviate the pain in the syringed portion.
  • the pharmaceutical preparation may contain a small amount of a non-toxic adjuvant material, such as wetting agent, emulsifying agent, pH buffer agent and the like.
  • a non-toxic adjuvant material such as wetting agent, emulsifying agent, pH buffer agent and the like.
  • the non-toxic adjuvant material may include, but not limited to, sodium acetate, sorbitan monolaurate, triethanolamine and triethanolamine oleate.
  • composition of the invention may further contain stabilizer, antioxidant, binding agent, colorant, flavouring, excipient such as antiseptic and thickening agent, carrier and diluent.
  • ⁇ i()8> First, 2X ATP was divided to the 384 well dishes for the fluorescent measurement by 5 ⁇ H.. Then, SU11248 prepared with 150 nM, 50 nM, 15 nM, 5 nM, 1.5 nM and 0.5 nM were treated with 96 pin dish. To eusure the correctness of the reaction, each sample was prepared with pairs and the control tests of a group having no SU11248/a group to which the c-kit protein was not added/a group of phospho-pept ide 0%/a group of phospho-peptide 100% were performed at the same time.
  • the solution in which the c-kit protein and the substrate peptide therefore were mixed was applied by 5 ⁇ l and then the reaction was carried out at 37 0 C for 45 minutes.
  • the development solution was applied by 5 ⁇ i, the reaction was conducted at room temperature for 40 minutes, and then the stop solution was applied by 5 ⁇ l, thereby completing the reaction.
  • the final concentrations of the respective materials used for the reaction were ATP 500 U M, the c-kit (kinase) protein 1.5 ng and the peptide 2 ⁇ M, and the final concentrations of SU11248 were 30 nM, 10 nM, 3 nM, 1 nM, 0.3 nM and 0.1 nM.
  • the reaction conditions used in this test were the same as those of the experimental example 1-1, the final concentrations of the benzimidazole derivative SB-CK-I11 and the aminoquinoline derivative SB-CK- 141, which were used to examine the activity inhibiting effect, were respectively 100 ⁇ M, 30 ⁇ M, 10 ⁇ M, 3 uM, 1 ⁇ M, 0.3 ⁇ M and 0.1 ⁇ M.
  • the inhibiting rate as described in the experimental example 1-1, the degree of the inhibition of the c-kit protein activity was shown in Fig. 2 based on the values obtained with the device for measuring the fluorescent after the reaction was completed.
  • the used cell lines were HM3K0 (which was supplied from Dr. Y Funasaka-Kobe University School of Medicine) which was derived from the human, and the culture was carried out in the MEM culture media to which 10% fetal bovine serum was added, under the conditions of 37°C and 5% C(V).
  • the cultured HM3K0 cells were separated with 0.25% trypsin-EDTA, again provided to the 6-well plates in the same amount (2.4X10 cells/well) and then left as they were for 24 hours. After that, all of the culture media were removed, and replaced with the MEM culture media to which 1% fetal bovine serum was added and then again cultured for 24 hours.
  • SU11248 was applied with the final concentration of 50 nM. Then, after 24 hours, the stem cell factor (SCF), which binds specifically to the c-kit protein and thus induces the activation thereof, was applied to the HM3K0 cells with the final concentration of 50 ng/mt for 15 minutes, thereby inducing the activation of the c-kit protein.
  • SCF stem cell factor
  • the nutrtional toilet water of the invention was prepared with the following composition shown in Table 1.
  • the nutrtional cream of the invention was prepared with the following composition shown in Table 2.
  • the massage cream of the invention was prepared with the following composition shown in Table 3.
  • the benzimidazole amine derivative SB-CK- 111 and the aminoquinoline derivative SB-CK-141 have the effect of inhibiting the c-kit protein activity which is a cell surface protein of the melanocyte. Since it inhibits a cell signaling in the melanocyte, in which the c-kit protein participates, thereby regulating a function of the melanocyte and ultimately inhibiting the melanogenesis to exhibit the skin whitening effect, the composition for inhibiting the c-kit protein or composition for the skin whitening containing them can be usefully used as a cosmetic composition or pharmaceutical composition.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Cosmetics (AREA)

Abstract

L'invention concerne une composition permettant d'inhiber la protéine c-kit ou une composition pour blanchir la peau contenant au moins un des dérivés de benzimidazole amine et des dérivés d'aminoquinoline. Ladite composition inhibe une signalisation cellulaire dans le mélanocyte, auquel participe la protéine c-kit, ce qui permet de réguler une fonction du mélanocyte et, en définitive, d'inhiber la mélanogenèse pour présenter l'effet de blanchiment de la peau.
PCT/KR2006/001988 2006-01-06 2006-05-25 Composition pour inhiber des derives de benzimidazole amine contenant des proteines c-kit Ceased WO2007078034A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020060001810A KR100788161B1 (ko) 2006-01-06 2006-01-06 벤즈이미다졸 아민 유도체 또는 아미노퀴놀린 유도체를 함유하는 피부 미백용 조성물
KR10-2006-0001810 2006-01-06

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Cited By (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
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
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
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
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
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
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
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
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

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WO2002096879A1 (fr) * 2001-05-31 2002-12-05 Sanofi-Synthelabo Derives d'aminoquinoline et d'aminopyrridine et leur utilisation comme ligands d'adenosine a3
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Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021130638A1 (fr) 2019-12-24 2021-07-01 Carna Biosciences, Inc. Composés modulant la diacylglycérol kinase
EP4445902A2 (fr) 2019-12-24 2024-10-16 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
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)
US11692038B2 (en) 2020-02-14 2023-07-04 Gilead Sciences, Inc. Antibodies that bind chemokine (C-C motif) receptor 8 (CCR8)
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
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
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
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
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
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
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
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
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
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

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