title: Discovery of Narrow Spectrum Kinase Inhibitors: New Therapeutic Agents for the Treatment of COPD and Steroid-Resistant Asthma.
abstract: The discovery of a novel series of therapeutic agents that has been designed and optimized for treating chronic obstructive pulmonary disease is reported. The pharmacological strategy was based on the identification of compounds that inhibit a defined subset of kinase enzymes modulating inflammatory processes that would be effective against steroid refractory disease and exhibit a sustained duration of action after inhaled delivery.
authors.affiliation: Sygnature Discovery Limited, Biocity , Nottingham NG1 1GF, United Kingdom.
authors.forename: Stuart T
authors.initials: ST
authors.lastname: Onions
authors.affiliation: RespiVert Limited , 2 Royal College Street, The London Bioscience Innovation Centre, London NW1 0NH, United Kingdom.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ito
authors.affiliation: RespiVert Limited , 2 Royal College Street, The London Bioscience Innovation Centre, London NW1 0NH, United Kingdom.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Charron
authors.affiliation: Sygnature Discovery Limited, Biocity , Nottingham NG1 1GF, United Kingdom.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Brown
authors.affiliation: Sygnature Discovery Limited, Biocity , Nottingham NG1 1GF, United Kingdom.
authors.forename: Marie
authors.initials: M
authors.lastname: Colucci
authors.affiliation: RespiVert Limited , 2 Royal College Street, The London Bioscience Innovation Centre, London NW1 0NH, United Kingdom.
authors.forename: Fritz
authors.initials: F
authors.lastname: Frickel
authors.affiliation: RespiVert Limited , 2 Royal College Street, The London Bioscience Innovation Centre, London NW1 0NH, United Kingdom.
authors.forename: George
authors.initials: G
authors.lastname: Hardy
authors.affiliation: Sygnature Discovery Limited, Biocity , Nottingham NG1 1GF, United Kingdom.
authors.forename: Kevin
authors.initials: K
authors.lastname: Joly
authors.affiliation: CompChem Resource , Old Cottage Hospital, Homend, Ledbury, Herefordshire HR8 1ED, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: King-Underwood
authors.affiliation: Department of Physiology and Anatomy, Nihon University School of Pharmacy , 7-7-1, Narashinodai, Funabashi, Chiba 274-8555, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kizawa
authors.affiliation: Pneumolabs UK Limited , Harrow, Middlesex HA1 3UJ, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Knowles
authors.affiliation: RespiVert Limited , 2 Royal College Street, The London Bioscience Innovation Centre, London NW1 0NH, United Kingdom.
authors.forename: P John
authors.initials: PJ
authors.lastname: Murray
authors.affiliation: Sygnature Discovery Limited, Biocity , Nottingham NG1 1GF, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Novak
authors.affiliation: Sygnature Discovery Limited, Biocity , Nottingham NG1 1GF, United Kingdom.
authors.forename: Anjna
authors.initials: A
authors.lastname: Rani
authors.affiliation: RespiVert Limited , 2 Royal College Street, The London Bioscience Innovation Centre, London NW1 0NH, United Kingdom.
authors.forename: Garth
authors.initials: G
authors.lastname: Rapeport
authors.affiliation: Sygnature Discovery Limited, Biocity , Nottingham NG1 1GF, United Kingdom.
authors.forename: Alun
authors.initials: A
authors.lastname: Smith
authors.affiliation: RespiVert Limited , 2 Royal College Street, The London Bioscience Innovation Centre, London NW1 0NH, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Strong
authors.affiliation: Sygnature Discovery Limited, Biocity , Nottingham NG1 1GF, United Kingdom.
authors.forename: David M
authors.initials: DM
authors.lastname: Taddei
authors.affiliation: Sygnature Discovery Limited, Biocity , Nottingham NG1 1GF, United Kingdom.
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Williams
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004351:Drug Resistance / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology; D013329:Structure-Activity Relationship; D020298:U937 Cells
chemical_list: D047428:Protein Kinase Inhibitors; D013256:Steroids; D011494:Protein Kinases