WO2009064006A1 - γ-セクレターゼの新規基質EphA7を利用したスクリーニング方法 - Google Patents
γ-セクレターゼの新規基質EphA7を利用したスクリーニング方法 Download PDFInfo
- Publication number
- WO2009064006A1 WO2009064006A1 PCT/JP2008/070864 JP2008070864W WO2009064006A1 WO 2009064006 A1 WO2009064006 A1 WO 2009064006A1 JP 2008070864 W JP2008070864 W JP 2008070864W WO 2009064006 A1 WO2009064006 A1 WO 2009064006A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- epha7
- secretase
- screening method
- method utilizing
- novel substrate
- Prior art date
Links
- 108010055153 EphA7 Receptor Proteins 0.000 title abstract 6
- 102100021606 Ephrin type-A receptor 7 Human genes 0.000 title abstract 6
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 title abstract 5
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 title abstract 5
- 238000000034 method Methods 0.000 title abstract 2
- 238000012216 screening Methods 0.000 title abstract 2
- 239000000758 substrate Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 6
- 238000003776 cleavage reaction Methods 0.000 abstract 2
- 230000007017 scission Effects 0.000 abstract 2
- 239000012634 fragment Substances 0.000 abstract 1
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
- C12Q1/48—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase
- C12Q1/485—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase involving kinase
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/02—Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Enzymes And Modification Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
本発明は、γ-セクレターゼによるEphA7のプロセシングに影響を与える化合物をスクリーニングする方法であって、以下のステップ:
(i) 候補化合物の存在下および非存在下で、γ-セクレターゼまたはその生物学的に活性なその断片を含む第1の生物学的組成物を、EphA7を含む第2の生物学的組成物と接触させ;
(ii) 当該候補化合物の存在下と非存在下で、当該EphA7の開裂を測定し;
(iii) γ-セクレターゼによる当該EphA7の開裂に影響を与える当該候補化合物を選択し;そして
(iv) 前記(iii)で得られた候補化合物が、γ-セクレターゼによるEphA7のプロセシングに影響を与える化合物であると同定する、
ことを含む、上記方法を提供する。
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/742,312 US8530181B2 (en) | 2007-11-15 | 2008-11-17 | Method of screening for compounds which affect the cleavage of EphA7 byγ-secretase |
EP08849729A EP2219028B1 (en) | 2007-11-15 | 2008-11-17 | Screening method utilizing novel substrate epha7 for gamma-secretase |
JP2009541201A JP5580598B2 (ja) | 2007-11-15 | 2008-11-17 | γ−セクレターゼの新規基質EphA7を利用したスクリーニング方法 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US98820307P | 2007-11-15 | 2007-11-15 | |
US60/988,203 | 2007-11-15 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2009064006A1 true WO2009064006A1 (ja) | 2009-05-22 |
Family
ID=40638851
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2008/070864 WO2009064006A1 (ja) | 2007-11-15 | 2008-11-17 | γ-セクレターゼの新規基質EphA7を利用したスクリーニング方法 |
Country Status (4)
Country | Link |
---|---|
US (1) | US8530181B2 (ja) |
EP (1) | EP2219028B1 (ja) |
JP (1) | JP5580598B2 (ja) |
WO (1) | WO2009064006A1 (ja) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090191580A1 (en) * | 2007-07-19 | 2009-07-30 | Eisai R & D Management Co., Ltd. | METHOD OF SCREENING USING c-MET, A NOVEL SUBSTRATE FOR GAMMA-SECRETASE |
US20100190184A1 (en) * | 2007-08-01 | 2010-07-29 | Eisai R & D Management Co., Ltd. | Screening method utilizing novel substrate c-ret for gamma-secretase |
US8530181B2 (en) | 2007-11-15 | 2013-09-10 | Eisai R&D Management Co., Ltd. | Method of screening for compounds which affect the cleavage of EphA7 byγ-secretase |
EP2223999B1 (en) * | 2007-11-30 | 2017-10-18 | Eisai R&D Management Co., Ltd. | Epha4 polypeptide having novel activity and use thereof |
US8865426B2 (en) | 2010-12-17 | 2014-10-21 | Eisai R&D Management Co., Ltd. | Screening method using gelatinase-mediated EphA4 cleavage reaction as an indicator |
US9784751B2 (en) | 2011-04-25 | 2017-10-10 | Eisai R&D Management Co., Ltd. | Method for detecting neurological disease associated with cognitive impairment by measuring EphA4 extracellular domain |
MX2021015298A (es) | 2019-07-01 | 2022-01-18 | Eisai R&D Man Co Ltd | Anticuerpo anti-epha4 humano. |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006056467A1 (en) * | 2004-11-25 | 2006-06-01 | Cellzome Ag | Use of eph receptor inhibitors for the treatment of neurodegenerative diseases |
Family Cites Families (27)
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US255522A (en) * | 1882-03-28 | Valve for oil and water wells | ||
JP2824433B2 (ja) | 1988-12-09 | 1998-11-11 | 財団法人化学及血清療法研究所 | 新規なハイブリッドプロモーターおよびこれを組み込んだ外来遺伝子発現用ベクター |
CA1339413C (en) | 1988-06-24 | 1997-09-02 | Junichi Miyazaki | Exogenous gene expression vector containing chick .beta.-actin gene promoter |
JP3680114B2 (ja) | 1993-09-17 | 2005-08-10 | 敏一 中村 | 脳神経障害治療剤 |
US5902732A (en) * | 1995-10-04 | 1999-05-11 | Cytoscan Sciences Llc | Drug screening process measuring changes in cell volume |
AU6887698A (en) | 1997-04-08 | 1998-10-30 | Sugen, Inc. | Study and treatment of diseases related to specific cellular functions of receptor protein tyrosine kinases |
US20020068361A1 (en) * | 1997-04-08 | 2002-06-06 | Douglas Clary | Methods of evaluating specific cellular functions of receptor protein tyrosine kinases in a ligand independent manner |
US5876946A (en) * | 1997-06-03 | 1999-03-02 | Pharmacopeia, Inc. | High-throughput assay |
US20070026409A1 (en) * | 2001-08-14 | 2007-02-01 | The General Hospital Corporation | Nucleic acid and amino acid sequences involved in pain |
US20060241074A1 (en) * | 2001-08-14 | 2006-10-26 | The General Hospital Corporation | Methods for treatment of pain |
EP1478772A2 (en) | 2001-08-14 | 2004-11-24 | The General Hospital Corporation | Nucleic acid and amino acid sequences involved in pain |
JP2003169699A (ja) | 2001-12-10 | 2003-06-17 | Japan Science & Technology Corp | 特異的γプロテアーゼ阻害剤のスクリーニング方法 |
JP2004000060A (ja) | 2002-05-31 | 2004-01-08 | Otsuka Pharmaceut Co Ltd | アミロイドβ産生に影響を与える化合物のスクリーニング方法 |
CA2505764A1 (en) | 2002-11-26 | 2004-06-10 | Pharmacia & Upjohn Company Llc | Soluble notch-based substrates for gamma secretase and methods and compositions for using same |
JPWO2005045028A1 (ja) | 2003-11-10 | 2007-05-17 | 財団法人大阪産業振興機構 | セル・フリー・Notch切断分析方法及び薬剤スクリーニング方法 |
WO2005083086A2 (en) | 2004-02-27 | 2005-09-09 | Oncotherapy Science, Inc. | Epha4 as therapeutic target of prc and pdaca |
NZ553273A (en) | 2004-09-08 | 2009-11-27 | Univ Melbourne | Treating gliosis, glial scarring, inflammation or inhibition of a xonal growth in the nervous system with an antagonist of EphA4-mediated signalling |
GB0427023D0 (en) | 2004-12-09 | 2005-01-12 | Merck Sharp & Dohme | Assay method |
EP1947193A1 (en) | 2007-01-17 | 2008-07-23 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Screening method for anti-diabetic compounds |
WO2008150010A1 (ja) | 2007-06-08 | 2008-12-11 | Eisai R & D Management Co., Ltd. | γ-セクレターゼの新規基質EphA4を利用したスクリーニング方法 |
EP2183598A1 (en) * | 2007-07-13 | 2010-05-12 | Elan Pharmaceuticals Inc. | Compositions and methods for identifying substrate specificity of inhibitors of gamma secretase |
US20090191580A1 (en) * | 2007-07-19 | 2009-07-30 | Eisai R & D Management Co., Ltd. | METHOD OF SCREENING USING c-MET, A NOVEL SUBSTRATE FOR GAMMA-SECRETASE |
US20100190184A1 (en) * | 2007-08-01 | 2010-07-29 | Eisai R & D Management Co., Ltd. | Screening method utilizing novel substrate c-ret for gamma-secretase |
US20090163594A1 (en) * | 2007-10-31 | 2009-06-25 | Elan Pharmaceuticals, Inc. | Triple Assay System for Identifying Substrate Selectivity of Gamma Secretase Inhibitors |
US8530181B2 (en) | 2007-11-15 | 2013-09-10 | Eisai R&D Management Co., Ltd. | Method of screening for compounds which affect the cleavage of EphA7 byγ-secretase |
EP2223999B1 (en) * | 2007-11-30 | 2017-10-18 | Eisai R&D Management Co., Ltd. | Epha4 polypeptide having novel activity and use thereof |
US20100113415A1 (en) * | 2008-05-29 | 2010-05-06 | Rajapakse Hemaka A | Epha4 rtk inhibitors for treatment of neurological and neurodegenerative disorders and cancer |
-
2008
- 2008-11-17 US US12/742,312 patent/US8530181B2/en active Active
- 2008-11-17 EP EP08849729A patent/EP2219028B1/en not_active Not-in-force
- 2008-11-17 JP JP2009541201A patent/JP5580598B2/ja not_active Expired - Fee Related
- 2008-11-17 WO PCT/JP2008/070864 patent/WO2009064006A1/ja active Application Filing
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006056467A1 (en) * | 2004-11-25 | 2006-06-01 | Cellzome Ag | Use of eph receptor inhibitors for the treatment of neurodegenerative diseases |
Non-Patent Citations (4)
Title |
---|
GEORGAKOPOULOS A. ET AL.: "Metalloproteinase/ Presenilinl processing of ephrinB regulates EphB-induced Src phosphorylation and signaling", EMBO J, vol. 25, no. 6, 2006, pages 1242 - 1252, XP008129422 * |
HOLMBERG J ET AL.: "Regulation of repulsion versus adhesion by different splice forms of an Eph receptor", NATURE, vol. 408, no. 6809, 2000, pages 203 - 206, XP002547708 * |
MURPHY M.P. ET AL.: "g y-Secretase, Evidence for Multiple Proteolytic Activities and Influence of Membrane Positioning of Substrate on Generation of Amyloid Peptides of Varying Length", J BIOL CHEM, vol. 274, no. 17, 1999, pages 11914 - 11923, XP002254470 * |
NAKANISHI H. ET AL.: "ALL1 fusion proteins induce deregulation of EphA7 and ERK phosphorylation in human acute leukemias", PROC NATL ACAD SCI USA, vol. 104, no. 36, 4 September 2007 (2007-09-04), pages 14442 - 14447, XP008129901 * |
Also Published As
Publication number | Publication date |
---|---|
US20100255522A1 (en) | 2010-10-07 |
JPWO2009064006A1 (ja) | 2011-03-31 |
EP2219028A1 (en) | 2010-08-18 |
EP2219028B1 (en) | 2012-09-12 |
EP2219028A4 (en) | 2010-12-29 |
US8530181B2 (en) | 2013-09-10 |
JP5580598B2 (ja) | 2014-08-27 |
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