WO2017109709A3 - A high-throughput assay method for identifying allosteric nmda receptor modulators - Google Patents

A high-throughput assay method for identifying allosteric nmda receptor modulators Download PDF

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Publication number
WO2017109709A3
WO2017109709A3 PCT/IB2016/057843 IB2016057843W WO2017109709A3 WO 2017109709 A3 WO2017109709 A3 WO 2017109709A3 IB 2016057843 W IB2016057843 W IB 2016057843W WO 2017109709 A3 WO2017109709 A3 WO 2017109709A3
Authority
WO
WIPO (PCT)
Prior art keywords
throughput assay
binding
assay method
nmdars
nmda receptor
Prior art date
Application number
PCT/IB2016/057843
Other languages
French (fr)
Other versions
WO2017109709A2 (en
Inventor
Anke Bill
Luiz Miguel Quinn CAMARGO
Mary Ellen Digan
Hongqiu GUO
Hao-Ran RAO
Original Assignee
Novartis Ag
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 Novartis Ag filed Critical Novartis Ag
Publication of WO2017109709A2 publication Critical patent/WO2017109709A2/en
Publication of WO2017109709A3 publication Critical patent/WO2017109709A3/en

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Classifications

    • 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
    • G01N33/502—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 for testing non-proliferative effects
    • 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
    • G01N33/502—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 for testing non-proliferative effects
    • G01N33/5035—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 for testing non-proliferative effects on sub-cellular localization

Abstract

A novel, high-throughput assay and methods to study N-methyl-D-aspartate receptors (NMDARs). The method allows for rapid comparisons of different subunits, the ability to measure effects of agonists for both the glycine binding site and the glutamate binding 5 site. The methods leverage the use of weak glycine and glutamate sites binding antagonists rather than to ketamine or MK-801 to mitigate against cellular toxicity and to retain the ligand binding site in a ligand-free state. The method can use baculovirus vectors to introduce titratable amounts of different receptor subunits. The assay replicates the pharmacology of NMDARs in response to known antagonists and allosteric 10 modulators, as well as sensitivity to magnesium.
PCT/IB2016/057843 2015-12-22 2016-12-20 A high-throughput assay method for identifying allosteric nmda receptor modulators WO2017109709A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201562271034P 2015-12-22 2015-12-22
US62/271,034 2015-12-22

Publications (2)

Publication Number Publication Date
WO2017109709A2 WO2017109709A2 (en) 2017-06-29
WO2017109709A3 true WO2017109709A3 (en) 2017-08-17

Family

ID=57944459

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2016/057843 WO2017109709A2 (en) 2015-12-22 2016-12-20 A high-throughput assay method for identifying allosteric nmda receptor modulators

Country Status (1)

Country Link
WO (1) WO2017109709A2 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111982866B (en) * 2020-06-05 2022-05-20 中国科学院新疆理化技术研究所 Method for detecting ketamine by colorimetric fluorescence quenching dual-mode
WO2023021102A1 (en) * 2021-08-20 2023-02-23 Bayer Aktiengesellschaft Use of polypeptides with calcium indicator activity for identifying the activity of insecticidal proteins
CN114957445B (en) * 2022-05-31 2023-09-19 陕西脉元生物科技有限公司 NMDAR NR1 subunit, mutant of NMDAR, construction method and application thereof

Citations (4)

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EP0606734A1 (en) * 1992-12-11 1994-07-20 Allelix Biopharmaceuticals Inc. Human CNS receptors of the NMDA-R1 family
GB2291647A (en) * 1994-07-26 1996-01-31 Merck Sharp & Dohme Stable cell line expressing human NMDA R2B receptor submit
US5985586A (en) * 1993-04-20 1999-11-16 Sibia Neurosciences, Inc. Methods for identifying compounds that modulate the activity of human N-methyl-D-aspartate receptors
WO2015052226A1 (en) * 2013-10-11 2015-04-16 F. Hoffmann-La Roche Ag Thiazolopyrimidinones as modulators of nmda receptor activity

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US4399141A (en) 1977-09-19 1983-08-16 Merck & Co., Inc. 5-Alkyl or hydroxyalkyl substituted-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imines and anticonvulsant use thereof
US4477668A (en) 1982-04-07 1984-10-16 Merck & Co., Inc. Process for 5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine
AU5429794A (en) 1992-11-12 1994-06-08 Merck Sharp & Dohme Limited Cdnas encoding human nmda-22a receptor subunit and isoforms of the human nmda-r1 receptor subunit, transfected cell line expressing them
ATE346595T1 (en) 1994-02-08 2006-12-15 Nps Pharma Inc COMPOUNDS ACTING AT A NEW LOCATION OF RECEPTOR-DEPENDENT CALCIUM CHANNELS FOR THE TREATMENT OF NEUROLOGICAL DISEASES
US5871986A (en) 1994-09-23 1999-02-16 The General Hospital Corporation Use of a baculovirus to express and exogenous gene in a mammalian cell
US20060029546A1 (en) 2004-08-06 2006-02-09 Decode Genetics, Inc. Materials and methods for identifying anti-schizophrenic agents
US20110319416A1 (en) 2009-01-28 2011-12-29 Emory University Subunit Selective NMDA Receptor Antagonists For The Treatment Of Neurological Conditions

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0606734A1 (en) * 1992-12-11 1994-07-20 Allelix Biopharmaceuticals Inc. Human CNS receptors of the NMDA-R1 family
US5985586A (en) * 1993-04-20 1999-11-16 Sibia Neurosciences, Inc. Methods for identifying compounds that modulate the activity of human N-methyl-D-aspartate receptors
GB2291647A (en) * 1994-07-26 1996-01-31 Merck Sharp & Dohme Stable cell line expressing human NMDA R2B receptor submit
WO2015052226A1 (en) * 2013-10-11 2015-04-16 F. Hoffmann-La Roche Ag Thiazolopyrimidinones as modulators of nmda receptor activity

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
J. T. COYLE: "NMDA Receptor and Schizophrenia: A Brief History", SCHIZOPHRENIA BULLETIN, vol. 38, no. 5, 1 September 2012 (2012-09-01), pages 920 - 926, XP055370282, ISSN: 0586-7614, DOI: 10.1093/schbul/sbs076 *
K. B. HANSEN ET AL: "Implementation of a Fluorescence-Based Screening Assay Identifies Histamine H3 Receptor Antagonists Clobenpropit and Iodophenpropit as Subunit-Selective N-Methyl-D-Aspartate Receptor Antagonists", JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 333, no. 3, 2 March 2010 (2010-03-02), US, pages 650 - 662, XP055371146, ISSN: 0022-3565, DOI: 10.1124/jpet.110.166256 *

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