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WO2005103715A3 - Methods, compositions and compound assays for inhibiting amyloid-beta protein production - Google Patents

Methods, compositions and compound assays for inhibiting amyloid-beta protein production Download PDF

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Publication number
WO2005103715A3
WO2005103715A3 PCT/EP2005/051882 EP2005051882W WO2005103715A3 WO 2005103715 A3 WO2005103715 A3 WO 2005103715A3 EP 2005051882 W EP2005051882 W EP 2005051882W WO 2005103715 A3 WO2005103715 A3 WO 2005103715A3
Authority
WO
WIPO (PCT)
Prior art keywords
amyloid
beta
compositions
methods
protein production
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/EP2005/051882
Other languages
French (fr)
Other versions
WO2005103715A2 (en
Inventor
Koenraad Frederik Fl Spittaels
Marcel Hoffmann
Pascal Gerard Merchiers
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.)
Galapagos NV
Original Assignee
Galapagos NV
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
Priority claimed from PCT/EP2004/005624 external-priority patent/WO2005103689A1/en
Application filed by Galapagos NV filed Critical Galapagos NV
Publication of WO2005103715A2 publication Critical patent/WO2005103715A2/en
Publication of WO2005103715A3 publication Critical patent/WO2005103715A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C12N2310/111—Antisense spanning the whole gene, or a large part of it
    • 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
    • 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
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/50—Physical structure
    • C12N2310/53—Physical structure partially self-complementary or closed
    • 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
    • G01N2333/4709—Amyloid plaque core protein
    • 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)

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Neurology (AREA)
  • General Health & Medical Sciences (AREA)
  • Neurosurgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Psychiatry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Plant Pathology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

A method for identifying compounds that inhibit amyloid-beta precursor protein processing in cells, comprising contacting a test compound with a melanocortin receptor polypeptide, or fragment thereof, and measuring a compound-polypeptide property related to the production of amyloid-beta peptide. Cellular assays of the method measure indicators including second messenger and/or amyloid beta peptide levels. Therapeutic methods, and pharmaceutical compositions including effective amyloid-beta precursor processing-inhibiting amounts of melanocortin receptor inhibitors, are useful for treating conditions involving cognitive impairment such as Alzheimers Disease.
PCT/EP2005/051882 2004-04-27 2005-04-26 Methods, compositions and compound assays for inhibiting amyloid-beta protein production Ceased WO2005103715A2 (en)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
EP2004004521 2004-04-27
EPPCT/EP2004/004521 2004-04-27
EPPCT/EP2004/005624 2004-05-21
PCT/EP2004/005624 WO2005103689A1 (en) 2004-04-27 2004-05-21 Novel compounds for the treatment of alzheimer’s disease and methods for identifying same
EP2004011427 2004-10-08
EPPCT/EP2004/011427 2004-10-08

Publications (2)

Publication Number Publication Date
WO2005103715A2 WO2005103715A2 (en) 2005-11-03
WO2005103715A3 true WO2005103715A3 (en) 2006-08-03

Family

ID=35197591

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2005/051882 Ceased WO2005103715A2 (en) 2004-04-27 2005-04-26 Methods, compositions and compound assays for inhibiting amyloid-beta protein production

Country Status (1)

Country Link
WO (1) WO2005103715A2 (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001052880A1 (en) * 2000-01-18 2001-07-26 Merck & Co., Inc. Cyclic peptides as potent and selective melanocortin-4 receptor antagonists
US6287763B1 (en) * 1996-06-10 2001-09-11 Millennium Pharmaceuticals, Inc. Screening methods for compounds useful in the regulation of body weight

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6287763B1 (en) * 1996-06-10 2001-09-11 Millennium Pharmaceuticals, Inc. Screening methods for compounds useful in the regulation of body weight
WO2001052880A1 (en) * 2000-01-18 2001-07-26 Merck & Co., Inc. Cyclic peptides as potent and selective melanocortin-4 receptor antagonists

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
GALIMBERTI D ET AL: "ALPHA-MSH PEPTIDES INHIBIT PRODUCTION OF NITRIC OXIDE AND TUMOR NECROSIS FACTOR-ALPHA BY MICROGLIAL CELLS ACTIVATED WITH BETA-AMYLOID AND INTERFERON GAMMA", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, ACADEMIC PRESS INC. ORLANDO, FL, US, vol. 263, 16 September 1999 (1999-09-16), pages 251 - 256, XP000941934, ISSN: 0006-291X *
VOS T J ET AL: "Identification of 2-[2-[2-(5-Bromo-2-methoxyphenyl)-ethyl]-3-fluoro-p henyl]-4,5-dihydro-1H-imidazole (ML00253764) , a Small Molecule Melanocortin Receptor Antagonist That Effectively Reduces Tumor Induced Weight Loss in a Mouse Model", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 47, no. 7, 2004, pages 1602 - 1604, XP002312163, ISSN: 0022-2623 *

Also Published As

Publication number Publication date
WO2005103715A2 (en) 2005-11-03

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