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WO2007109324A3 - Potent and selective nav 1.7 sodium channel blockers - Google Patents

Potent and selective nav 1.7 sodium channel blockers Download PDF

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Publication number
WO2007109324A3
WO2007109324A3 PCT/US2007/007025 US2007007025W WO2007109324A3 WO 2007109324 A3 WO2007109324 A3 WO 2007109324A3 US 2007007025 W US2007007025 W US 2007007025W WO 2007109324 A3 WO2007109324 A3 WO 2007109324A3
Authority
WO
WIPO (PCT)
Prior art keywords
potent
selective
relates
sodium channel
channel blockers
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/US2007/007025
Other languages
French (fr)
Other versions
WO2007109324A2 (en
Inventor
Robert A Fraser
Robin Sherrington
Marcia L Macdonald
Mark Samuels
Scott Newman
Jian-Min Fu
Rajender Kamboj
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.)
Xenon Pharmaceuticals Inc
Original Assignee
Xenon Pharmaceuticals Inc
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 Xenon Pharmaceuticals Inc filed Critical Xenon Pharmaceuticals Inc
Publication of WO2007109324A2 publication Critical patent/WO2007109324A2/en
Anticipated expiration legal-status Critical
Publication of WO2007109324A3 publication Critical patent/WO2007109324A3/en
Ceased legal-status Critical Current

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    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
    • 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
    • G01N33/5082—Supracellular entities, e.g. tissue, organisms
    • G01N33/5088—Supracellular entities, e.g. tissue, organisms of vertebrates
    • 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
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6872—Intracellular protein regulatory factors and their receptors, e.g. including ion channels
    • 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
    • G01N33/94—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors
    • G01N33/9486—Analgesics, e.g. opiates, aspirine
    • C—CHEMISTRY; METALLURGY
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
    • 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
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/136—Screening for pharmacological compounds
    • C—CHEMISTRY; METALLURGY
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    • C12Q2600/00—Oligonucleotides characterized by their use
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    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/172—Haplotypes
    • 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
    • G01N2500/04—Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/28—Neurological disorders
    • G01N2800/2842—Pain, e.g. neuropathic pain, psychogenic pain

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

Abstract

The present invention relates to the discovery that mutations in Nav1.7 are causative of Congenital Indifference to Pain (CIP) in humans. The invention also relates to methods of utilizing the Nav1.7 gene and expression products thereof for the screening and identification of therapeutic agents, including small organic compounds, which are selective for Nav1.7, and are useful in the treatment of pain and other Nav1.7-mediated disorders. The invention discloses potent and selective small molecule inhibitors of Nay1.7 and also relates to methods of using these compounds to treat or otherwise ameliorate such disorders.
PCT/US2007/007025 2006-03-21 2007-03-21 Potent and selective nav 1.7 sodium channel blockers Ceased WO2007109324A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US78453506P 2006-03-21 2006-03-21
US60/784,535 2006-03-21

Publications (2)

Publication Number Publication Date
WO2007109324A2 WO2007109324A2 (en) 2007-09-27
WO2007109324A3 true WO2007109324A3 (en) 2008-11-27

Family

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Family Applications (1)

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PCT/US2007/007025 Ceased WO2007109324A2 (en) 2006-03-21 2007-03-21 Potent and selective nav 1.7 sodium channel blockers

Country Status (1)

Country Link
WO (1) WO2007109324A2 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
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US9624280B2 (en) 2013-10-03 2017-04-18 Janssen Biotech, Inc. Protoxin-II variants and methods of use
US10463714B2 (en) 2015-04-02 2019-11-05 Janssen Biotech, Inc. Protoxin-II variants and methods of use
US10995125B2 (en) 2015-03-03 2021-05-04 Janssen Biotech, Inc. Protoxin-II variants and methods of use

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US9278088B2 (en) 2002-02-19 2016-03-08 Xenon Pharmaceuticals Inc. Methods for identifying analgesic agents
US7659082B2 (en) 2002-02-19 2010-02-09 Xenon Pharmaceuticals Inc. Methods for identifying analgesic agents
WO2008101029A2 (en) * 2007-02-13 2008-08-21 Xenon Pharmaceuticals Inc. Use of thiazole, oxazole and imidazole compounds for the treatment of sodium channel-mediated diseases or conditions
WO2008147864A2 (en) * 2007-05-22 2008-12-04 Xenon Pharmaceuticals Inc. Methods of using piperazine compounds in treating sodium channel-mediated diseases or conditions
WO2009033027A2 (en) * 2007-09-05 2009-03-12 Medtronic, Inc. Suppression of scn9a gene expression and/or function for the treatment of pain
WO2009143277A2 (en) * 2008-05-20 2009-11-26 Intradigm Corporation Compositions comprising hscn9a sirna and methods of use thereof
WO2010071983A1 (en) 2008-12-22 2010-07-01 Universite Laval Mutated voltage-gated sodium channel nav alpha subunit for identification of modulators
BRPI0924225A2 (en) * 2009-02-02 2016-10-11 Chromocell Corp nav-expressing cell lines and methods of use
CN102781963B (en) * 2009-10-27 2018-02-16 Ucb医药有限公司 Functionally modified NAv1.7 antibody
US9234037B2 (en) 2009-10-27 2016-01-12 Ucb Biopharma Sprl Method to generate antibodies to ion channels
GB0922435D0 (en) 2009-12-22 2010-02-03 Ucb Pharma Sa Method
GB0922434D0 (en) 2009-12-22 2010-02-03 Ucb Pharma Sa antibodies and fragments thereof
US8486647B2 (en) 2010-06-09 2013-07-16 Regeneron Pharmaceuticals, Inc. Neuropeptide release assay for sodium channels
US8871996B2 (en) 2010-06-09 2014-10-28 Regeneron Pharmaceuticals, Inc. Mice expressing human voltage-gated sodium channels
SG188438A1 (en) 2010-09-13 2013-05-31 Novartis Ag Triazine-oxadiazoles
WO2012049555A1 (en) 2010-10-13 2012-04-19 Lupin Limited Spirocyclic compounds as voltage-gated sodium channel modulators
SG191993A1 (en) 2011-01-18 2013-08-30 Amgen Inc Nav1.7 knockout mice and uses thereof
US9340590B2 (en) * 2011-03-16 2016-05-17 Amgen Inc. Potent and selective inhibitors of NaV1.3 and NaV1.7
ES2541535T3 (en) * 2011-05-12 2015-07-21 Regeneron Pharmaceuticals, Inc. Neuropeptide release test for sodium channels
WO2012162732A1 (en) * 2011-06-02 2012-12-06 The University Of Queensland Assays for sodium ion channel modulators and uses thereof
US10414808B2 (en) 2012-05-18 2019-09-17 Janssen Biotech, Inc. Huwentoxin-IV variants and methods of use
US9102751B2 (en) 2012-05-18 2015-08-11 Janssen Biotech, Inc. Huwentoxin-IV variants and methods of use
EP3973981A1 (en) * 2012-05-18 2022-03-30 Janssen Biotech, Inc. Huwentoxin-iv variants and methods of use
EP2970408B1 (en) 2013-03-12 2018-01-10 Amgen Inc. Potent and selective inhibitors of nav1.7
AR096927A1 (en) 2013-03-12 2016-02-10 Amgen Inc POWERFUL AND SELECTIVE INHIBITORS OF NaV1.7
KR20150127618A (en) 2013-03-14 2015-11-17 리제너론 파아마슈티컬스, 인크. Human antibodies to nav1.7
US8986694B1 (en) 2014-07-15 2015-03-24 Kymab Limited Targeting human nav1.7 variants for treatment of pain
US9067998B1 (en) 2014-07-15 2015-06-30 Kymab Limited Targeting PD-1 variants for treatment of cancer
US9914769B2 (en) 2014-07-15 2018-03-13 Kymab Limited Precision medicine for cholesterol treatment
US9045545B1 (en) 2014-07-15 2015-06-02 Kymab Limited Precision medicine by targeting PD-L1 variants for treatment of cancer
US8992927B1 (en) 2014-07-15 2015-03-31 Kymab Limited Targeting human NAV1.7 variants for treatment of pain
WO2015102929A1 (en) 2013-12-30 2015-07-09 Novartis Ag Tricyclic sulfonamide derivatives
GB201403775D0 (en) 2014-03-04 2014-04-16 Kymab Ltd Antibodies, uses & methods
WO2015151001A1 (en) 2014-03-29 2015-10-08 Lupin Limited Sulfonamide compounds as voltage gated sodium channel modulators
US9139648B1 (en) 2014-07-15 2015-09-22 Kymab Limited Precision medicine by targeting human NAV1.9 variants for treatment of pain
TW201722938A (en) 2015-09-04 2017-07-01 魯賓有限公司 Sulfonamide compounds as voltage-gated sodium channel modulators
KR102531889B1 (en) 2016-06-20 2023-05-17 키맵 리미티드 Anti-PD-L1 and IL-2 cytokines
WO2018083248A1 (en) 2016-11-03 2018-05-11 Kymab Limited Antibodies, combinations comprising antibodies, biomarkers, uses & methods
WO2018138585A1 (en) 2017-01-24 2018-08-02 Olipass Corporation Scn9a antisense pain killer
WO2018163077A1 (en) 2017-03-08 2018-09-13 Lupin Limited Indanyl compounds as voltage gated sodium channel modulators
GB201711208D0 (en) 2017-07-12 2017-08-23 Iontas Ltd Ion channel inhibitors

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Non-Patent Citations (3)

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Title
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9624280B2 (en) 2013-10-03 2017-04-18 Janssen Biotech, Inc. Protoxin-II variants and methods of use
US10975129B2 (en) 2013-10-03 2021-04-13 Janssen Biotech, Inc. Protoxin-II variants and methods of use
US10995125B2 (en) 2015-03-03 2021-05-04 Janssen Biotech, Inc. Protoxin-II variants and methods of use
US10463714B2 (en) 2015-04-02 2019-11-05 Janssen Biotech, Inc. Protoxin-II variants and methods of use
US11083776B2 (en) 2015-04-02 2021-08-10 Janssen Biotech, Inc. Protoxin-II variants and methods of use

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