Kathrine J Smith

Summary

Affiliation: GlaxoSmithKline Research and Development
Country: USA

Publications

  1. doi request reprint BACE-1 inhibitors part 3: identification of hydroxy ethylamines (HEAs) with nanomolar potency in cells
    Paul Beswick
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R and D, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK
    Bioorg Med Chem Lett 18:1022-6. 2008
  2. ncbi request reprint The structure of MSK1 reveals a novel autoinhibitory conformation for a dual kinase protein
    Kathrine J Smith
    Discovery Research, GlaxoSmithKline, Third Ave, Harlow, Essex, CM19 5AW, United Kingdom
    Structure 12:1067-77. 2004
  3. doi request reprint BACE-1 hydroxyethylamine inhibitors using novel edge-to-face interaction with Arg-296
    Brian Clarke
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R and D, New Frontiers Science Park, Harlow, Essex, UK
    Bioorg Med Chem Lett 20:4639-44. 2010
  4. pmc Structural variation and inhibitor binding in polypeptide deformylase from four different bacterial species
    Kathrine J Smith
    GlaxoSmithKline, Harlow, Essex CM19 5AW, UK
    Protein Sci 12:349-60. 2003
  5. doi request reprint Discovery of N-[(2S)-5-(6-fluoro-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide, a novel clinical AMPA receptor positive modulator
    Simon E Ward
    Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK
    J Med Chem 53:5801-12. 2010
  6. doi request reprint Second generation of hydroxyethylamine BACE-1 inhibitors: optimizing potency and oral bioavailability
    Nicolas Charrier
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Park, Harlow, Essex, UK
    J Med Chem 51:3313-7. 2008
  7. doi request reprint BACE-1 inhibitors part 2: identification of hydroxy ethylamines (HEAs) with reduced peptidic character
    Brian Clarke
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R and D, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom
    Bioorg Med Chem Lett 18:1017-21. 2008
  8. doi request reprint Second generation of BACE-1 inhibitors part 3: Towards non hydroxyethylamine transition state mimetics
    Nicolas Charrier
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R and D, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom
    Bioorg Med Chem Lett 19:3674-8. 2009
  9. doi request reprint Second generation of BACE-1 inhibitors. Part 1: The need for improved pharmacokinetics
    Nicolas Charrier
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R and D, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom
    Bioorg Med Chem Lett 19:3664-8. 2009
  10. doi request reprint Second generation of BACE-1 inhibitors part 2: Optimisation of the non-prime side substituent
    Nicolas Charrier
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R and D, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom
    Bioorg Med Chem Lett 19:3669-73. 2009

Collaborators

Detail Information

Publications12

  1. doi request reprint BACE-1 inhibitors part 3: identification of hydroxy ethylamines (HEAs) with nanomolar potency in cells
    Paul Beswick
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R and D, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK
    Bioorg Med Chem Lett 18:1022-6. 2008
    ..Optimization of the non-prime side of our inhibitors and introduction of a 6-membered sultam substituent binding to Asn-294 as well as a fluorine in the C-2 position led to derivatives with nanomolar potency in cell-based assays...
  2. ncbi request reprint The structure of MSK1 reveals a novel autoinhibitory conformation for a dual kinase protein
    Kathrine J Smith
    Discovery Research, GlaxoSmithKline, Third Ave, Harlow, Essex, CM19 5AW, United Kingdom
    Structure 12:1067-77. 2004
    ..The new three-stranded beta sheet occupies a position equivalent to the N terminus of the alphaC helix in active protein kinases...
  3. doi request reprint BACE-1 hydroxyethylamine inhibitors using novel edge-to-face interaction with Arg-296
    Brian Clarke
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R and D, New Frontiers Science Park, Harlow, Essex, UK
    Bioorg Med Chem Lett 20:4639-44. 2010
    ..These inhibitors interact with the non prime side of the enzyme using a novel edge-to-face interaction with Arg-296...
  4. pmc Structural variation and inhibitor binding in polypeptide deformylase from four different bacterial species
    Kathrine J Smith
    GlaxoSmithKline, Harlow, Essex CM19 5AW, UK
    Protein Sci 12:349-60. 2003
    ..Understanding the similarities and subtle differences in active site structure between species will help to design broad-spectrum polypeptide deformylase inhibitor molecules...
  5. doi request reprint Discovery of N-[(2S)-5-(6-fluoro-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide, a novel clinical AMPA receptor positive modulator
    Simon E Ward
    Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK
    J Med Chem 53:5801-12. 2010
    ..These discoveries led to 17i, a potent, efficacious CNS penetrant molecule with an excellent pharmacokinetic profile across preclinical species, which is well tolerated and is also orally bioavailable in humans...
  6. doi request reprint Second generation of hydroxyethylamine BACE-1 inhibitors: optimizing potency and oral bioavailability
    Nicolas Charrier
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Park, Harlow, Essex, UK
    J Med Chem 51:3313-7. 2008
    ..Optimization of a first generation of BACE-1 inhibitors led to the discovery of novel hydroxyethylamines (HEAs) bearing a tricyclic nonprime side. These derivatives have nanomolar cell potency and are orally bioavailable...
  7. doi request reprint BACE-1 inhibitors part 2: identification of hydroxy ethylamines (HEAs) with reduced peptidic character
    Brian Clarke
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R and D, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom
    Bioorg Med Chem Lett 18:1017-21. 2008
    ..Inhibitors with nanosmolar potency and high selectivity were identified. Depending on the nature of the P(1)(') and P(2)(') substituents, two different binding modes were observed in X-ray co-crystal structures...
  8. doi request reprint Second generation of BACE-1 inhibitors part 3: Towards non hydroxyethylamine transition state mimetics
    Nicolas Charrier
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R and D, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom
    Bioorg Med Chem Lett 19:3674-8. 2009
    ..In this Letter, we describe our successful strategy for the optimization of oral bioavailability and also give insights into the design of compounds with the potential for improved brain penetration...
  9. doi request reprint Second generation of BACE-1 inhibitors. Part 1: The need for improved pharmacokinetics
    Nicolas Charrier
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R and D, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom
    Bioorg Med Chem Lett 19:3664-8. 2009
    ..In this Letter, we describe the reasons that led us to favor a second generation of inhibitors for further in vivo studies...
  10. doi request reprint Second generation of BACE-1 inhibitors part 2: Optimisation of the non-prime side substituent
    Nicolas Charrier
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R and D, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom
    Bioorg Med Chem Lett 19:3669-73. 2009
    ..This Letter describes the discovery of such inhibitors...
  11. doi request reprint BACE-1 inhibitors part 1: identification of novel hydroxy ethylamines (HEAs)
    Brian Clarke
    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R and D, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom
    Bioorg Med Chem Lett 18:1011-6. 2008
    ..These inhibitors were capable of lowering amyloid production in a cell-based assay...
  12. pmc Allelic variation of MHC structure alters peptide ligands to induce atypical partial agonistic CD8+ T cell function
    Dong Gyun Lim
    Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Institutes of Medicine, Boston, MA 02115 5817, USA
    J Exp Med 198:99-109. 2003
    ..These data indicate that MAPLs can induce atypical partial agonistic T cell function through structural and biochemical mechanisms similar to altered peptide ligands...