[go: up one dir, main page]

WO2023043271A1 - Procédé de caractérisation d'un répondeur à un inhibiteur de cage pour une thérapie contre le cancer - Google Patents

Procédé de caractérisation d'un répondeur à un inhibiteur de cage pour une thérapie contre le cancer Download PDF

Info

Publication number
WO2023043271A1
WO2023043271A1 PCT/KR2022/013904 KR2022013904W WO2023043271A1 WO 2023043271 A1 WO2023043271 A1 WO 2023043271A1 KR 2022013904 W KR2022013904 W KR 2022013904W WO 2023043271 A1 WO2023043271 A1 WO 2023043271A1
Authority
WO
WIPO (PCT)
Prior art keywords
cancer
cage
group
formula
inhibitor
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/KR2022/013904
Other languages
English (en)
Korean (ko)
Inventor
전도용
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.)
L Base Co Ltd
Original Assignee
L Base 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 L Base Co Ltd filed Critical L Base Co Ltd
Publication of WO2023043271A1 publication Critical patent/WO2023043271A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids

Definitions

  • Another object of the present invention is to provide a kit for determining a cancer patient requiring administration of a CAGE inhibitor.
  • the CAGE inhibitor is a compound represented by the general formula X-AQTGTGKT, wherein X is a compound represented by the following formula (1), or a pharmaceutically acceptable salt thereof:
  • the biological sample is blood, whole blood, plasma, urine, saliva, tissue, cell, organ, bone marrow, fine needle aspiration specimen, core needle biopsy specimen, and vacuum aspiration biopsy. It may be one or more selected from the group consisting of specimens, but is not limited thereto.
  • the composition may be used to determine a cancer patient whose expression level of CAGE is increased compared to a control group as a cancer patient requiring administration of a CAGE inhibitor, but is not limited thereto.
  • the present invention is a method for characterizing responders to CAGE inhibitors for anticancer treatment, and confirms that an amidated analog compound of AQTGTGKT peptide has excellent anticancer effect and increased half-life, and in particular, in cancer cell lines overexpressing CAGE, the AQTGTGKT analog compound It was completed by confirming that this excellent anti-cancer effect was shown.
  • A is alanine
  • Q is glutamine
  • T is threonine
  • G is glycine
  • K is lysine
  • R 3 is hydrogen, a C 1 to C 6 alkyl group, a phenyl group, a C 1 to C 3 alkoxy group, a morpholyl group, or CF 3 ;
  • the pharmaceutical composition according to the present invention may further include suitable carriers, excipients and/or diluents commonly used to prepare pharmaceutical compositions in addition to active ingredients.
  • suitable carriers excipients and/or diluents commonly used to prepare pharmaceutical compositions in addition to active ingredients.
  • it can be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories and sterile injection solutions according to conventional methods.
  • Thr(OBn)GlyThr(OBn)GlyLys(Cbz)Thr(OBn)OBn compound 12; 12.7 g, 12.0 mmol in ethyl acetate (150 mL) and N,N -dimethylformamide (25 mL) , 1.0 equiv) and BocGlnOH (3.25 g, 13.2 mmol, 1.1 equiv) was added N,N-diisopropylethylamine (4.60 mL, 26.4 mmol, 2.2 equiv). The mixture was stirred at room temperature under an inert atmosphere and HATU (5.47 g, 14.4 mmol, 1.20 equiv) was added.
  • reaction mixture was diluted with ethyl acetate then washed with NH 4 Cl (saturated aqueous), NaHCO 3 (saturated aqueous) and brine.
  • the organics were dried (Na 2 SO 4 ), filtered and concentrated under reduced pressure.
  • the residue was purified on a 25 g column with a 15-50% ethyl acetate in heptane gradient to give compound 16-2 as a colorless solid (360 mg, 70% yield).
  • the dried material was purified on a 30 g C18 column using a 5-30% acetonitrile (0.1% formic acid) gradient in water (0.1% formic acid) and lyophilized to give the compound as a colorless solid (7.0 mg, 10% yield). 19-2 was obtained.
  • Ph-AQTGTGKT (Compound 19-4) was synthesized by reacting Compound 14 and Compound 14 according to Reaction Scheme 15 with Compound 17-4 obtained according to Reaction Scheme 14 below to obtain Ph-AQTGTGKT as the final target compound.
  • the present invention is a CAGE inhibitor and an analog compound of the novel oligopeptide AQTGTGKT and a method for characterizing a responder to the compound, which was completed by confirming that the compound exhibits excellent anticancer effects in cancer overexpressing CAGE.
  • the compound has a small molecular weight compared to antibodies, so there is less concern about immune reactions, and in addition to being easy to penetrate into tissues, it has a more excellent inhibitory effect on cancer cell proliferation, and it can stably exist in human blood, so it is useful as an anticancer agent.
  • responders to the compound of the present invention can be selected through a companion diagnostic method based on the measurement of CAGE expression levels, thereby maximizing the anticancer effect of the compound and reducing medical costs. do.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Analytical Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pathology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Biochemistry (AREA)
  • Organic Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Cell Biology (AREA)
  • Zoology (AREA)
  • General Physics & Mathematics (AREA)
  • Genetics & Genomics (AREA)
  • Food Science & Technology (AREA)
  • Wood Science & Technology (AREA)
  • Oncology (AREA)
  • Biophysics (AREA)
  • Hospice & Palliative Care (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un nouveau composé analogue d'oligopeptide AQTGTGKT qui est un inhibiteur de CAGE et un procédé pour caractériser un répondeur au composé, et a été finalisée en confirmant que le composé présente un excellent effet anticancéreux sur un cancer surexprimant CAGE. Ayant un faible poids moléculaire par rapport aux anticorps, le composé est moins susceptible d'induire une réponse immunitaire et pénètre facilement dans les tissus. De plus, le composé a non seulement un excellent effet d'inhibition de la prolifération de cellules cancéreuses, mais peut également demeurer de manière stable dans le sang humain, et il pourrait donc être utilisé en tant qu'agent anticancéreux utile. En particulier, du fait que les répondeurs au composé de la présente invention peuvent être sélectionnés par l'intermédiaire d'un procédé de diagnostic associé basé sur la mesure du niveau d'expression de CAGE, l'effet anticancéreux du composé pourrait être maximisé tandis qu'un effet de réduction des coûts médicaux pouvant être obtenu simultanément.
PCT/KR2022/013904 2021-09-17 2022-09-16 Procédé de caractérisation d'un répondeur à un inhibiteur de cage pour une thérapie contre le cancer Ceased WO2023043271A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2021-0125268 2021-09-17
KR1020210125268A KR102494749B1 (ko) 2021-09-17 2021-09-17 암 치료용 cage 저해제에 대한 반응자 특성화 방법

Publications (1)

Publication Number Publication Date
WO2023043271A1 true WO2023043271A1 (fr) 2023-03-23

Family

ID=85224413

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2022/013904 Ceased WO2023043271A1 (fr) 2021-09-17 2022-09-16 Procédé de caractérisation d'un répondeur à un inhibiteur de cage pour une thérapie contre le cancer

Country Status (2)

Country Link
KR (1) KR102494749B1 (fr)
WO (1) WO2023043271A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20120099440A (ko) * 2009-10-22 2012-09-10 임페리얼 이노베이션스 리미티드 Ｇａｄｄ45β를 표적으로 하는 물질
WO2016099188A1 (fr) * 2014-12-18 2016-06-23 주식회사 엘베이스 Peptide ayant huit séquences d'acides aminés dérivées de cage et conservant une activité anticancéreuse et une activité visant à promouvoir la sensibilité à un médicament anticancéreux de cellules cancéreuses résistant à des médicaments anti-cancéreux
KR20210118764A (ko) * 2020-03-23 2021-10-01 주식회사 엘베이스 암의 예방 또는 치료용 약학적 조성물

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101311717B1 (ko) 2011-07-05 2013-09-25 한국과학기술연구원 대장암 진단용 단백질 마커 멜라노트랜스페린 및 이에 대한 항체를 포함하는 대장암 진단 키트

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20120099440A (ko) * 2009-10-22 2012-09-10 임페리얼 이노베이션스 리미티드 Ｇａｄｄ45β를 표적으로 하는 물질
WO2016099188A1 (fr) * 2014-12-18 2016-06-23 주식회사 엘베이스 Peptide ayant huit séquences d'acides aminés dérivées de cage et conservant une activité anticancéreuse et une activité visant à promouvoir la sensibilité à un médicament anticancéreux de cellules cancéreuses résistant à des médicaments anti-cancéreux
KR20210118764A (ko) * 2020-03-23 2021-10-01 주식회사 엘베이스 암의 예방 또는 치료용 약학적 조성물

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
MINJEONG YEON, JAEWHAN BYUN, HYUNA KIM, MISUN KIM, HYUN SUK JUNG, DOYONG JEON, YOUNGMI KIM, DOOIL JEOUNG: "CAGE Binds to Beclin1, Regulates Autophagic Flux and CAGE-Derived Peptide Confers Sensitivity to Anti-cancer Drugs in Non-small Cell Lung Cancer Cells", FRONTIERS IN ONCOLOGY, vol. 8, XP055756617, DOI: 10.3389/fonc.2018.00599 *
MINJEONG YEON, MISUN KIM, YOOJUNG KWON, SEUNGHEON LEE, HYE-IN JO, JEONGSEON YEO, DOOIL JEOUNG: "Interaction of CAGE with Beclin-1 regulates autophagic flux and confers drug-resistance in non-small lung cancer cells", KSBMB INTERNATIONAL CONFERENCE 2019; 2019.06.02~05, KOREA SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, KOREA, 1 January 2019 (2019-01-01) - 5 June 2019 (2019-06-05), Korea, pages 108 - 108, XP009544615 *
YOUNGMI KIM, HYUNA KIM, DEOKBUM PARK, HANSOO LEE, YUN SIL LEE, JONGSEON CHOE, YOUNG MYEONG KIM, DOYONG JEON, DOOIL JEOUNG: "The pentapeptide Gly-Thr-Gly-Lys-Thr confers sensitivity to anti-cancer drugs by inhibition of CAGE binding to GSK3β and decreasing the expression of cyclinD1", ONCOTARGET, vol. 8, no. 8, 21 February 2017 (2017-02-21), pages 13632 - 13651, XP055756625, DOI: 10.18632/oncotarget.14621 *

Also Published As

Publication number Publication date
KR102494749B1 (ko) 2023-02-06

Similar Documents

Publication Publication Date Title
WO2018194380A2 (fr) Molécule de liaison spécifique pour la protéine lrig-1 et son utilisation
WO2020080853A1 (fr) Molécule de liaison spécifique à la protéine lrig-1, et utilisation associée
WO2010047509A9 (fr) Anticorps dirigé contre le dr5 présentant une meilleure affinité et une meilleure stabilité, et composition destinée a prévenir ou traiter le cancer et contenant cet anticorps
WO2018004065A1 (fr) Nouveau dérivé d'aryléthane et composition pharmaceutique contenant ce dérivé comme principe actif
WO2022211537A1 (fr) Nouveau conjugué immunoactif d'analogue d'interleukine 2 et son procédé de préparation
WO2020263063A1 (fr) Utilisation thérapeutique, pour les maladies hépathiques, d'un triple agoniste ayant une activité par rapport à tous les récepteurs du glucagon, de glp-1 et de gip, ou conjugué de ceux-ci
WO2022035302A1 (fr) Composition pharmaceutique à effet hypotenseur comprenant un activateur triple présentant une activité pour tous les récepteurs du glucagon, de la glp-1, et de la gip
WO2024155094A1 (fr) Antigène de surface de lymphocyte t régulateur, et anticorps se liant de manière spécifique à celui-ci
WO2021194228A1 (fr) Composition pharmaceutique pour la prévention ou le traitement du cancer
WO2022197100A1 (fr) Composition pharmaceutique pour améliorer l'effet anticancéreux d'un médicament anticancéreux
WO2022139493A1 (fr) NOUVEAU PEPTIDE POUVANT INHIBER LA SIGNALISATION DU TGF-β ET SON UTILISATION
WO2023043271A1 (fr) Procédé de caractérisation d'un répondeur à un inhibiteur de cage pour une thérapie contre le cancer
WO2022035271A1 (fr) Composition pharmaceutique comprenant un conjugué persistant de triple activateur utilisé comme principe actif
WO2023043269A1 (fr) Composition pharmaceutique pour moduler une réponse immunitaire
WO2022015082A1 (fr) Utilisation thérapeutique d'un dérivé du glucagon ou d'un conjugué de celui-ci pour une maladie hépatique
WO2021006714A1 (fr) Composition pour la prévention, l'atténuation ou le traitement du cancer résistant aux inhibiteurs de point de contrôle immunitaire
WO2021066573A1 (fr) Nouveau composé et son utilisation dans le traitement de maladies auto-immunes
WO2013077618A1 (fr) Composition pharmaceutique contenant un anticorps anti-kiaa1114 en tant que principe actif pour la prévention ou le traitement du cancer induit par une surexpression de kiaa1114
WO2022139538A1 (fr) Nouveau triple activateur activant tous les récepteurs du glucagon, du glp-1 et du gip, et son utilisation
WO2022203219A1 (fr) Composition pharmaceutique pour la prévention ou le traitement du cancer
WO2022015115A1 (fr) Utilisation thérapeutique d'une combinaison contenant un conjugué à action prolongée triplement agoniste ou un triple agoniste
WO2022055168A1 (fr) Nouveau dérivé de prymidodiazépine et son utilisation
WO2019132610A1 (fr) Protéine de fusion baf57 recombinante et son utilisation
WO2024136573A1 (fr) Nouvel activateur triple ayant une activité sur tous les récepteurs glp-1, gip et glucagon, et composition pharmaceutique pour prévenir ou traiter l'obésité le comprenant
WO2025259060A1 (fr) Triple activateur ayant une activité sur tous les récepteurs du glp-1, du gip et du glucagon, et composition pharmaceutique pour la prévention ou le traitement de maladies métaboliques lipidiques le comprenant

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: 22870355

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 22870355

Country of ref document: EP

Kind code of ref document: A1