WO2004072646A1 - Agents de diagnostic et de traitement destines aux maladies associees au recepteur 5 couple a la proteine g (gpr5) - Google Patents

Agents de diagnostic et de traitement destines aux maladies associees au recepteur 5 couple a la proteine g (gpr5) Download PDF

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Publication number
WO2004072646A1
WO2004072646A1 PCT/EP2004/000881 EP2004000881W WO2004072646A1 WO 2004072646 A1 WO2004072646 A1 WO 2004072646A1 EP 2004000881 W EP2004000881 W EP 2004000881W WO 2004072646 A1 WO2004072646 A1 WO 2004072646A1
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WO
WIPO (PCT)
Prior art keywords
gpr5
diseases
disorders
polypeptide
inflammation
Prior art date
Application number
PCT/EP2004/000881
Other languages
English (en)
Inventor
Stefan Golz
Ulf Brüggemeier
Holger Summer
Original Assignee
Bayer Healthcare 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 Bayer Healthcare Ag filed Critical Bayer Healthcare Ag
Publication of WO2004072646A1 publication Critical patent/WO2004072646A1/fr

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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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors

Definitions

  • the ligand binding sites of GPCRs ' are believed to comprise hydrophilic sockets formed by several GPCR transmembrane domains.
  • the hydrophilic sockets are surrounded by hydrophobic residues of the GPCRs.
  • the hydrophilic side of each GPCR transmembrane helix is postulated to face inward and form a polar ligand binding site.
  • TM3 is being implicated with several GPCRs as having a ligand binding site, such as the TM3 aspartate residue.
  • TM5 serines, a TM6 asparagine, and TM6 or TM7 phenylalanines or tyrosines also are implicated in ligand binding.
  • Fig. 1 shows the nucleotide sequence of a GPR5 receptor polynucleotide (SEQ ID NO:l).
  • GPR5 polynucleotide within the meaning of the invention, shall be understood as being a nucleic acid molecule selected from a group consisting of
  • the invention relates to nucleic acid sequences that hybridize with such
  • a gene sequence contained in all samples at relatively constant quantity is typically utilized for sample amplification efficiency normalization.
  • This approach suffers from several drawbacks.
  • the method requires that each sample has equal input amounts of the nucleic acid and that the amplification efficiency between samples is identical until the time of analysis.
  • a number of diseases are associated with changes in the copy number of a certain gene.
  • the real-time PCR method can be used to determine if the patient has copy number alterations which are known to be linked with diseases that are associated with the symptoms the patient has.
  • Different host cells which have specific cellular machinery and characteristic mechanisms for post-translational activities (e.g., CHO, HeLa, MDCK, HEK293, and WI38), are available from the American Type Culture Collection (ATCC; 10801 University Boulevard, Manassas, VA 20110-2209) and can be chosen to ensure the correct modification and processing of the foreign protein.
  • ATCC American Type Culture Collection
  • Ribozymes are RNA molecules with catalytic activity [Uhlmann, (1987)]. Ribozymes can be used to inhibit gene function by cleaving an RNA sequence, as is known in the art. The mechanism of ribozyme action involves sequence-specific hybridization of the ribozyme molecule to complementary target RNA, followed by endonucleolytic cleavage. Examples include • engineered hammerhead motif ribozyme molecules that can specifically and efficiently catalyze endonucleolytic cleavage of specific nucleotide sequences.
  • the test compound can be labelled with 125 I, 35 S, 14 C, or 3 H, either directly or indirectly, and the radioisotope detected by direct counting of radioemmission or by scintillation counting.
  • the test compound can be enzymatically labelled with, for example, horseradish peroxidase, alkaline phosphatase, or luciferase, and the enzymatic label detected by determination of conversion of an appropriate substrate to product.
  • non-ionic detergents such as n-oct
  • GST-immobilized complexes include immunodetection of complexes using antibodies reactive with GPR5 or target molecule, as well as enzyme-linked assays which rely on detecting an enzymatic activity associated with GPR5 or target molecule.
  • candidate modulating compounds can be identified by searching databases containing compounds along with information on their molecular structure. Such a search seeks compounds having structures that match the determined active site structure and that interact with the groups defining the active site. Such a search can be manual, but is preferably computer assisted. These compounds found from this search are potential GPR5 modulating compounds.
  • CNS disorders such as mild cognitive impairment, age-associated memory impairment, age-related cognitive decline, vascular cognitive impairment, attention deficit disorders, attention deficit hyperactivity disorders, and memory disturbances in children with learning disabilities are also considered to be CNS disorders.
  • denatured protein from reverse phase HPLC separation is obtained in quantities up to 75 mg. This denatured protein is used to immunize mice or rabbits using standard protocols; about 100 ⁇ g are adequate for immunization of a mouse, while up to 1 mg might be used to immunize a rabbit.
  • the denatured protein is radioiodinated and used to screen potential murine B-cell hybridomas for those which produce antibody. This procedure requires only small quantities of protein, such that 20 mg is sufficient for labeling and screening of several thousand clones.
  • GPR5 e.g., high ionic strength buffers in the presence of detergent. Then, the column is eluted under conditions that disrupt antibody/protein binding (e.g., a buffer of pH 2-3 or a high concentration of a chaotrope such as urea or thiocyanate ion), and GPR5 is collected.
  • a chaotrope such as urea or thiocyanate ion

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Cell Biology (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne un GPR5 humain qui est associé aux maladies hématologiques, aux maladies cardio-vasculaires, aux troubles du système nerveux périphérique et central, à l'inflammation, aux maladies urologiques et aux troubles du système gastro-entérologique. La présente invention se rapporte également à des dosages qui permettent d'identifier des composés utiles dans le traitement ou dans la prévention des maladies hématologiques, des maladies cardio-vasculaires, des troubles du système nerveux périphérique et central, de l'inflammation, des maladies urologiques et des troubles du système gastro-entérologique. Cette invention concerne également des composés qui se lient à GPR5 et/ou qui activent ou qui inhibent l'activité de GPR5 ainsi que des compositions pharmaceutiques comprenant de tels composés.
PCT/EP2004/000881 2003-02-13 2004-01-31 Agents de diagnostic et de traitement destines aux maladies associees au recepteur 5 couple a la proteine g (gpr5) WO2004072646A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP03003111.6 2003-02-13
EP03003111 2003-02-13

Publications (1)

Publication Number Publication Date
WO2004072646A1 true WO2004072646A1 (fr) 2004-08-26

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2004/000881 WO2004072646A1 (fr) 2003-02-13 2004-01-31 Agents de diagnostic et de traitement destines aux maladies associees au recepteur 5 couple a la proteine g (gpr5)

Country Status (1)

Country Link
WO (1) WO2004072646A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2641915A1 (fr) * 2012-03-15 2013-09-25 Richard Kroczek Anticorps contre le récepteur de chimiokine XCR1
JP2014527396A (ja) * 2011-09-01 2014-10-16 エーザイ・アール・アンド・ディー・マネジメント株式会社 抗ヒトｘｃｒ１抗体
AU2013276993B2 (en) * 2007-08-13 2016-03-31 Takeda Pharmaceutical Company Limited IVIG Modulations of Chemokines for Treatment of Multiple Sclerosis, Alzheimer's Disease, and Parkinson's Disease

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001064754A1 (fr) * 2000-03-03 2001-09-07 Kyowa Hakko Kogyo Co., Ltd. Anticorps a recombinaison genique et son fragment

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001064754A1 (fr) * 2000-03-03 2001-09-07 Kyowa Hakko Kogyo Co., Ltd. Anticorps a recombinaison genique et son fragment

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CAIRNS C M ET AL: "Lymphotactin expression by engineered myeloma cells drives tumor regression: mediation by CD4+ and CD8+ T cells and neutrophils expressing XCR1 receptor.", JOURNAL OF IMMUNOLOGY (BALTIMORE, MD.: 1950) UNITED STATES 1 JUL 2001, vol. 167, no. 1, 1 July 2001 (2001-07-01), pages 57 - 65, XP002279610, ISSN: 0022-1767 *
HUANG HUI ET AL: "Neutrophils and B cells express XCR1 receptor and chemotactically respond to lymphotactin", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 281, no. 2, 23 February 2001 (2001-02-23), pages 378 - 382, XP002279608, ISSN: 0006-291X *
SHAN LIXIN ET AL: "Identification of viral macrophage inflammatory protein (vMIP)-II as a ligand for GPR5/XCR1", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 268, no. 3, 24 February 2000 (2000-02-24), pages 938 - 941, XP002279611, ISSN: 0006-291X *
YOSHIDA TETSUYA ET AL: "Identification of single C motif-1/lymphotactin receptor XCR1", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 273, no. 26, 26 June 1998 (1998-06-26), pages 16551 - 16554, XP002279609, ISSN: 0021-9258 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2013276993B2 (en) * 2007-08-13 2016-03-31 Takeda Pharmaceutical Company Limited IVIG Modulations of Chemokines for Treatment of Multiple Sclerosis, Alzheimer's Disease, and Parkinson's Disease
JP2014527396A (ja) * 2011-09-01 2014-10-16 エーザイ・アール・アンド・ディー・マネジメント株式会社 抗ヒトｘｃｒ１抗体
EP2641915A1 (fr) * 2012-03-15 2013-09-25 Richard Kroczek Anticorps contre le récepteur de chimiokine XCR1

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