WO2001002601A3 - Cell-based assay systems for examining hcv ns3 protease activity - Google Patents

Cell-based assay systems for examining hcv ns3 protease activity Download PDF

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Publication number
WO2001002601A3
WO2001002601A3 PCT/US2000/018590 US0018590W WO0102601A3 WO 2001002601 A3 WO2001002601 A3 WO 2001002601A3 US 0018590 W US0018590 W US 0018590W WO 0102601 A3 WO0102601 A3 WO 0102601A3
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WIPO (PCT)
Prior art keywords
activity
protease activity
assays
protease
inhibiting
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PCT/US2000/018590
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French (fr)
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WO2001002601A2 (en
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Anu Bansal
Claudio Pasquinelli
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Du Pont Pharm Co
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Publication date
Application filed by Du Pont Pharm Co filed Critical Du Pont Pharm Co
Priority to AU59204/00A priority Critical patent/AU5920400A/en
Publication of WO2001002601A2 publication Critical patent/WO2001002601A2/en
Publication of WO2001002601A3 publication Critical patent/WO2001002601A3/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/69—Boron compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • C07F5/025—Boronic and borinic acid compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0827—Tripeptides containing heteroatoms different from O, S, or N
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1027—Tetrapeptides containing heteroatoms different from O, S, or N
    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/503—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from viruses
    • C12N9/506—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from viruses derived from RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/24011—Flaviviridae
    • C12N2770/24211—Hepacivirus, e.g. hepatitis C virus, hepatitis G virus
    • C12N2770/24222—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Virology (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Oncology (AREA)
  • Epidemiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Biomedical Technology (AREA)
  • Communicable Diseases (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Enzymes And Modification Thereof (AREA)

Abstract

Assays for identifying levels of hepatitis C virus NS3 protease activity are provided herein, and involve the transfection into mammalian cells of cDNA corresponding to HCV nucleic acid sequences encoding both the viral NS3 protease activity and an NS3 polyprotein precursor substrate including an NS3 cleavage site. The presence of mature, processed substrate in lysates obtained from the transfected cells is indicative of the level of activity of the NS3 protease in the cells. These assays can thus also be used as a screen to examine the activity of a particular compound in inhibiting NS3 protease activity, by conducting the assays in the absence and presence of the compound. The degree to which NS3 protease activity is expressed in the former assays over the latter is indicative of the compound's activity in inhibiting the NS3 protein substrate cleavage, and thus also, of inhibiting HCV replication.
PCT/US2000/018590 1999-07-07 2000-07-07 Cell-based assay systems for examining hcv ns3 protease activity WO2001002601A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU59204/00A AU5920400A (en) 1999-07-07 2000-07-07 Cell-based assay systems for examining hcv ns3 protease activity

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US14256199P 1999-07-07 1999-07-07
US60/142,561 1999-07-07

Publications (2)

Publication Number Publication Date
WO2001002601A2 WO2001002601A2 (en) 2001-01-11
WO2001002601A3 true WO2001002601A3 (en) 2001-07-26

Family

ID=22500325

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/US2000/018590 WO2001002601A2 (en) 1999-07-07 2000-07-07 Cell-based assay systems for examining hcv ns3 protease activity
PCT/US2000/018655 WO2001002424A2 (en) 1999-07-07 2000-07-07 Peptide boronic acid inhibitors of hepatitis c virus protease

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/US2000/018655 WO2001002424A2 (en) 1999-07-07 2000-07-07 Peptide boronic acid inhibitors of hepatitis c virus protease

Country Status (4)

Country Link
EP (1) EP1196436A2 (en)
AU (2) AU5788800A (en)
CA (1) CA2376965A1 (en)
WO (2) WO2001002601A2 (en)

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US6713446B2 (en) 2001-01-25 2004-03-30 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Formulation of boronic acid compounds
US7119072B2 (en) 2002-01-30 2006-10-10 Boehringer Ingelheim (Canada) Ltd. Macrocyclic peptides active against the hepatitis C virus
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US7112572B2 (en) 2002-09-09 2006-09-26 Trigen Limited Multivalent metal salts of boronic acids
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Also Published As

Publication number Publication date
AU5788800A (en) 2001-01-22
EP1196436A2 (en) 2002-04-17
AU5920400A (en) 2001-01-22
CA2376965A1 (en) 2001-01-11
WO2001002424A3 (en) 2001-07-19
WO2001002601A2 (en) 2001-01-11
WO2001002424A2 (en) 2001-01-11

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