Karen J Gregory

Summary

Affiliation: Vanderbilt University
Country: USA

Publications

  1. pmc Allosteric modulation of metabotropic glutamate receptors: structural insights and therapeutic potential
    Karen J Gregory
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232 0697, USA
    Neuropharmacology 60:66-81. 2011
  2. pmc Exploration of Allosteric Agonism Structure-Activity Relationships within an Acetylene Series of Metabotropic Glutamate Receptor 5 (mGlu5) Positive Allosteric Modulators (PAMs): Discovery of 5-((3-Fluorophenyl)ethynyl)-N-(3-methyloxetan-3-yl)picolinamide
    Mark Turlington
    Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Center for Structural Biology, and Vanderbilt Institute for Chemical Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States
    J Med Chem 56:7976-96. 2013
  3. pmc Unique signaling profiles of positive allosteric modulators of metabotropic glutamate receptor subtype 5 determine differences in in vivo activity
    Jerri M Rook
    Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232 0697, USA
    Biol Psychiatry 73:501-9. 2013
  4. pmc Probing the metabotropic glutamate receptor 5 (mGlu₅) positive allosteric modulator (PAM) binding pocket: discovery of point mutations that engender a "molecular switch" in PAM pharmacology
    Karen J Gregory
    Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232 0697, USA
    Mol Pharmacol 83:991-1006. 2013
  5. pmc Selective actions of novel allosteric modulators reveal functional heteromers of metabotropic glutamate receptors in the CNS
    Shen Yin
    Department of Pharmacology and the Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee 37232, and Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia
    J Neurosci 34:79-94. 2014
  6. pmc Investigating metabotropic glutamate receptor 5 allosteric modulator cooperativity, affinity, and agonism: enriching structure-function studies and structure-activity relationships
    Karen J Gregory
    Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Mol Pharmacol 82:860-75. 2012
  7. pmc Identification of specific ligand-receptor interactions that govern binding and cooperativity of diverse modulators to a common metabotropic glutamate receptor 5 allosteric site
    Karen J Gregory
    Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Center for Structural Biology, Department of Chemistry, and Institute for Chemical Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States
    ACS Chem Neurosci 5:282-95. 2014
  8. ncbi request reprint Pharmacology of metabotropic glutamate receptor allosteric modulators: structural basis and therapeutic potential for CNS disorders
    Karen J Gregory
    Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    Prog Mol Biol Transl Sci 115:61-121. 2013
  9. pmc Allosteric modulation of metabotropic glutamate receptors
    Douglas J Sheffler
    Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    Adv Pharmacol 62:37-77. 2011
  10. pmc Optimization of an ether series of mGlu5 positive allosteric modulators: molecular determinants of MPEP-site interaction crossover
    Jason T Manka
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 22:6481-5. 2012

Collaborators

  • Shaun R Stauffer
  • Jens Meiler
  • Kyle A Emmitte
  • Thomas M Bridges
  • Thomas Steckler
  • Alice L Rodriguez
  • Craig W Lindsley
  • P Jeffrey Conn
  • Colleen M Niswender
  • Jerri M Rook
  • Meredith J Noetzel
  • Paige N Vinson
  • Ya Zhou
  • J Scott Daniels
  • Jason T Manka
  • Shen Yin
  • Mark Turlington
  • Zixiu Xiang
  • Rocco D Gogliotti
  • Carrie K Jones
  • Douglas J Sheffler
  • Kari A Johnson
  • Nidhi Jalan-Sakrikar
  • Rocio Zamorano
  • Kiran K Gogi
  • Carrie Jones
  • Hyekyung P Cho
  • Aspen Chun
  • Elizabeth D Nguyen
  • F Edward Dudek
  • Wendy A Pouliot
  • Richard Williams
  • Satya Jadhav
  • Elizabeth J Herman
  • Claire Mackie
  • Gregor J Macdonald
  • José M Bartolomé
  • Hilde Lavreysen
  • C David Weaver
  • Kiran Gogi
  • Emily Days

Detail Information

Publications10

  1. pmc Allosteric modulation of metabotropic glutamate receptors: structural insights and therapeutic potential
    Karen J Gregory
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232 0697, USA
    Neuropharmacology 60:66-81. 2011
    ..In the absence of a class C GPCR crystal structure, this approach has shown promise with respect to the interpretation of mutagenesis data and understanding structure-activity relationships of allosteric modulator pharmacophores...
  2. pmc Exploration of Allosteric Agonism Structure-Activity Relationships within an Acetylene Series of Metabotropic Glutamate Receptor 5 (mGlu5) Positive Allosteric Modulators (PAMs): Discovery of 5-((3-Fluorophenyl)ethynyl)-N-(3-methyloxetan-3-yl)picolinamide
    Mark Turlington
    Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Center for Structural Biology, and Vanderbilt Institute for Chemical Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States
    J Med Chem 56:7976-96. 2013
    ..PAM 38t (ML254) will be useful to probe the relative contribution of cooperativity and allosteric agonism to the adverse effect liability and neurotoxicity associated with this class of mGlu5 PAMs. ..
  3. pmc Unique signaling profiles of positive allosteric modulators of metabotropic glutamate receptor subtype 5 determine differences in in vivo activity
    Jerri M Rook
    Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232 0697, USA
    Biol Psychiatry 73:501-9. 2013
    ..This mechanism may be critical to maintaining normal activity-dependence of mGlu5 activation and achieving optimal in vivo effects...
  4. pmc Probing the metabotropic glutamate receptor 5 (mGlu₅) positive allosteric modulator (PAM) binding pocket: discovery of point mutations that engender a "molecular switch" in PAM pharmacology
    Karen J Gregory
    Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232 0697, USA
    Mol Pharmacol 83:991-1006. 2013
    ..Interestingly, we identified two point mutations in TMs 6 and 7 that, when mutated, engender a mode switch in the pharmacology of certain PAMs...
  5. pmc Selective actions of novel allosteric modulators reveal functional heteromers of metabotropic glutamate receptors in the CNS
    Shen Yin
    Department of Pharmacology and the Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee 37232, and Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia
    J Neurosci 34:79-94. 2014
    ..These data greatly extend our current understanding of mGlu receptor interaction and function and provide compelling evidence that mGlu receptors can function as heteromers in intact brain circuits. ..
  6. pmc Investigating metabotropic glutamate receptor 5 allosteric modulator cooperativity, affinity, and agonism: enriching structure-function studies and structure-activity relationships
    Karen J Gregory
    Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Mol Pharmacol 82:860-75. 2012
    ..This model can be applied to PAM and NAM potency curves in combination with maximal fold-shift data to derive reliable estimates of modulator affinities...
  7. pmc Identification of specific ligand-receptor interactions that govern binding and cooperativity of diverse modulators to a common metabotropic glutamate receptor 5 allosteric site
    Karen J Gregory
    Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Center for Structural Biology, Department of Chemistry, and Institute for Chemical Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States
    ACS Chem Neurosci 5:282-95. 2014
    ..Our findings highlight the subtleties of allosteric modulator binding to mGlu5 and demonstrate the utility in incorporating SAR information to strengthen the interpretation and analyses of docking and mutational data...
  8. ncbi request reprint Pharmacology of metabotropic glutamate receptor allosteric modulators: structural basis and therapeutic potential for CNS disorders
    Karen J Gregory
    Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    Prog Mol Biol Transl Sci 115:61-121. 2013
    ....
  9. pmc Allosteric modulation of metabotropic glutamate receptors
    Douglas J Sheffler
    Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    Adv Pharmacol 62:37-77. 2011
    ..Studies continue to validate the therapeutic utility of mGlu allosteric modulators as a potential therapeutic approach for a number of disorders including anxiety, schizophrenia, Parkinson's disease, and Fragile X syndrome...
  10. pmc Optimization of an ether series of mGlu5 positive allosteric modulators: molecular determinants of MPEP-site interaction crossover
    Jason T Manka
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 22:6481-5. 2012
    ..These studies suggest that potent PAMs within topologically similar chemotypes can be developed to preferentially interact or not interact with the MPEP allosteric binding site...