DK2904406T3 - Fremgangsmåde til bestemmelse af den ved atr-inhibition optrædende, forøgede dna-beskadigelse - Google Patents

Fremgangsmåde til bestemmelse af den ved atr-inhibition optrædende, forøgede dna-beskadigelse Download PDF

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Publication number
DK2904406T3
DK2904406T3 DK13779673.6T DK13779673T DK2904406T3 DK 2904406 T3 DK2904406 T3 DK 2904406T3 DK 13779673 T DK13779673 T DK 13779673T DK 2904406 T3 DK2904406 T3 DK 2904406T3
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blood
cells
compound
atr
pbs
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DK13779673.6T
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Susanna Falcon
Philip Reaper
John Pollard
Nicola Jane Curtin
Tao Chen
Fiona Kay Middleton
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Vertex Pharma
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    • 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
    • G01N33/6875—Nucleoproteins
    • 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
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5047—Cells of the immune system
    • 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
    • G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
    • G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
    • G01N2333/4701—Details
    • G01N2333/4703—Regulators; Modulating activity
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/91—Transferases (2.)
    • G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2440/00—Post-translational modifications [PTMs] in chemical analysis of biological material
    • G01N2440/14—Post-translational modifications [PTMs] in chemical analysis of biological material phosphorylation

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Cell Biology (AREA)
  • General Physics & Mathematics (AREA)
  • Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Biotechnology (AREA)
  • Analytical Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Toxicology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Claims (6)

1. Fremgangsmåde til monitering af ATR-hæmning (ATR-inhibition) i et individ ved måling af yII2AX-niveauer i blodet, idet fremgangsmåden omfatter: a) behandling af blodprøver med et DNA-beskadigende middel; idet blodprøverne hentes fra individet med forskellige tidsrum; og idet individet er blevet behandlet med en ATR-hæmmer; og idet blodprøverne fikseres mindre end 3 timer efter udsættelsen for det DNA-beskadigende middel; b) isolation af de hvide blodceller fra blodprøverne; og c) måling af γΗ2AX-n i vcaueme i de hvide blodlegemer ved anvendelse af antistof, der er specific for γΗ2ΑΧ.
2. Fremgangsmåde ifølge krav 1, hvor: a) det DNA-beskadigende middel er 4-nitroquinolin; eller b) det DNA-beskadigende middel er UV.
3. Fremgangsmåde ifølge krav 1, hvor de hvide blodlegemer isoleres med en samtidig fixering og lysering af røde blodlegemer i blodprøven, efterfulgt af centrifugering.
4. Fremgangsmåde ifølge krav 1, hvor målingen af yH2AX-niveauer tilvejebringes ved gennemstrømnings-cytometri; ved immunofluorescens; eller ved western-bloting.
5. Fremgangsmåde ifølge krav 1, hvor målingen af yH2AX-niveauer tilvejebringes i CD3+ hvide blodlegemer.
6. Fremgangsmåde ifølge krav 1, hvor ATR-inhibitoren er:
eller et pharmaceutisk accepterbart salt deraf.
DK13779673.6T 2012-10-04 2013-10-03 Fremgangsmåde til bestemmelse af den ved atr-inhibition optrædende, forøgede dna-beskadigelse DK2904406T3 (da)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201261709384P 2012-10-04 2012-10-04
PCT/US2013/063254 WO2014055756A1 (en) 2012-10-04 2013-10-03 Method for measuring atr inhibition mediated increases in dna damage

Publications (1)

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DK2904406T3 true DK2904406T3 (da) 2018-06-18

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US (2) US8999632B2 (da)
EP (1) EP2904406B1 (da)
DK (1) DK2904406T3 (da)
WO (1) WO2014055756A1 (da)

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ES2921576T3 (es) 2008-12-19 2022-08-29 Vertex Pharma Compuestos útiles como inhibidores de la quinasa ATR
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CN106496173A (zh) 2011-09-30 2017-03-15 沃泰克斯药物股份有限公司 用于制备可用作atr激酶抑制剂的化合物的方法
CN108478577A (zh) 2012-04-05 2018-09-04 沃泰克斯药物股份有限公司 可用作atr激酶抑制剂的化合物及其组合疗法
DK2904406T3 (da) 2012-10-04 2018-06-18 Vertex Pharma Fremgangsmåde til bestemmelse af den ved atr-inhibition optrædende, forøgede dna-beskadigelse
CN110579435B (zh) 2012-10-15 2023-09-26 纳诺赛莱克特生物医药股份有限公司 颗粒分选的系统、设备和方法
SI2941432T1 (en) 2012-12-07 2018-07-31 Vertex Pharmaceuticals Incorporated 2-AMINO-6-FLUORO-N- (5-FLUORO-4- (4- (4- (OXETHAN-3-YL) PIPERAZIN-1-CARBONYL) PIPERIDIN-1-YLIPRIDIN-3-YL) 1,5 ALFA) PYRIMIDINE-3-CARBOXAMIDE AS ATR KINAZE INHIBITOR
PT3077397T (pt) 2013-12-06 2020-01-22 Vertex Pharma Composto de 2-amino-6-fluoro-n-[5-fluoro-piridin-3-il]pirazolo[1,5-a]pirimidin-3-carboxamida útil como inibidor da atr quinase, a sua preparação, diferentes formas sólidas e derivados radiomarcados do mesmo
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MX2018008507A (es) * 2016-01-11 2019-07-04 Merrimack Pharmaceuticals Inc Inhibición de proteína relacionada con ataxia telangiectasia y rad3 (atr).
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WO2018029117A1 (en) * 2016-08-10 2018-02-15 Rheinisch-Westfälische Technische Hochschule Aachen (RWTH) New atr inhibitors for the use in cancer therapy
EA039513B1 (ru) * 2017-01-09 2022-02-04 Селатор Фармасьютикалз, Инк. Ингибитор атаксии-телеангиэкстазии и rad3-родственного белка (atr) и содержащие его липосомные композиции
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KR20210066837A (ko) 2018-09-26 2021-06-07 메르크 파텐트 게엠베하 암 치료를 위한 pd-1 안타고니스트, atr 억제제 및 백금화제의 조합
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