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 Biased mGlu5-Positive Allosteric Modulators Provide In Vivo Efficacy without Potentiating mGlu5 Modulation of NMDAR Currents
    Jerri M Rook
    Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA
    Neuron 86:1029-40. 2015
  8. 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
  9. doi 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
  10. 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

Collaborators

  • Shaun R Stauffer
  • Jens Meiler
  • Thomas M Bridges
  • Thomas Steckler
  • Kyle A Emmitte
  • Jesus Alcazar
  • Robert W Gould
  • Alice L Rodriguez
  • Craig W Lindsley
  • Jerri M Rook
  • P Jeffrey Conn
  • Colleen M Niswender
  • Paige N Vinson
  • J Scott Daniels
  • Zixiu Xiang
  • Meredith J Noetzel
  • Carrie K Jones
  • Ya Zhou
  • Jason T Manka
  • Kari A Johnson
  • Shen Yin
  • Hilde Lavreysen
  • Claire Mackie
  • Gregor J Macdonald
  • Mark Turlington
  • Rocco D Gogliotti
  • Douglas J Sheffler
  • Rebekah L Collier
  • Daniel J Foster
  • Analisa D Thompson
  • Ayan Ghoshal
  • Nellie Byun
  • Jonathan W Dickerson
  • Michael T Nedelcovych
  • Michael Bubser
  • José M Bartolomé-Nebreda
  • Xiaohui Lv
  • Susana Conde-Ceide
  • John C Talpos
  • Nidhi Jalan-Sakrikar
  • Rocio Zamorano
  • Kiran K Gogi
  • Aspen Chun
  • Elizabeth D Nguyen
  • Carrie Jones
  • Wendy A Pouliot
  • F Edward Dudek
  • Hyekyung P Cho
  • Satya Jadhav
  • Elizabeth J Herman
  • Richard Williams
  • José M Bartolomé
  • Emily Days
  • C David Weaver
  • Kiran Gogi

Detail Information

Publications12

  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 Biased mGlu5-Positive Allosteric Modulators Provide In Vivo Efficacy without Potentiating mGlu5 Modulation of NMDAR Currents
    Jerri M Rook
    Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA
    Neuron 86:1029-40. 2015
    ..These data provide surprising new mechanistic insights into the actions of mGlu5 PAMs and suggest that modulation of NMDAR currents is not critical for in vivo efficacy. VIDEO ABSTRACT. ..
  8. 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...
  9. doi 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
    ....
  10. 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...
  11. 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...
  12. pmc Molecular Insights into Metabotropic Glutamate Receptor Allosteric Modulation
    Karen J Gregory
    Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia K J G and Vanderbilt Center for Neuroscience Drug Discovery and Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee P J C
    Mol Pharmacol 88:188-202. 2015
    ..In recent years we have made significant progress in our understanding of this molecular complexity coupled with an increased understanding of the structural basis of mGlu allosteric modulation. ..