title: Discovery and characterization of a G protein-biased agonist that inhibits β-arrestin recruitment to the D2 dopamine receptor.
abstract: A high-throughput screening campaign was conducted to interrogate a 380,000+ small-molecule library for novel D2 dopamine receptor modulators using a calcium mobilization assay. Active agonist compounds from the primary screen were examined for orthogonal D2 dopamine receptor signaling activities including cAMP modulation and β-arrestin recruitment. Although the majority of the subsequently confirmed hits activated all signaling pathways tested, several compounds showed a diminished ability to stimulate β-arrestin recruitment. One such compound (MLS1547; 5-chloro-7-[(4-pyridin-2-ylpiperazin-1-yl)methyl]quinolin-8-ol) is a highly efficacious agonist at D2 receptor-mediated G protein-linked signaling, but does not recruit β-arrestin as demonstrated using two different assays. This compound does, however, antagonize dopamine-stimulated β-arrestin recruitment to the D2 receptor. In an effort to investigate the chemical scaffold of MLS1547 further, we characterized a set of 24 analogs of MLS1547 with respect to their ability to inhibit cAMP accumulation or stimulate β-arrestin recruitment. A number of the analogs were similar to MLS1547 in that they displayed agonist activity for inhibiting cAMP accumulation, but did not stimulate β-arrestin recruitment (i.e., they were highly biased). In contrast, other analogs displayed various degrees of G protein signaling bias. These results provided the basis to use pharmacophore modeling and molecular docking analyses to build a preliminary structure-activity relationship of the functionally selective properties of this series of compounds. In summary, we have identified and characterized a novel G protein-biased agonist of the D2 dopamine receptor and identified structural features that may contribute to its biased signaling properties.
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.) freeb@ninds.nih.gov.
authors.forename: R Benjamin
authors.initials: RB
authors.lastname: Free
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Lani S
authors.initials: LS
authors.lastname: Chun
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Amy E
authors.initials: AE
authors.lastname: Moritz
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Brittney N
authors.initials: BN
authors.lastname: Miller
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Trevor B
authors.initials: TB
authors.lastname: Doyle
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Jennie L
authors.initials: JL
authors.lastname: Conroy
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Adrian
authors.initials: A
authors.lastname: Padron
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Julie A
authors.initials: JA
authors.lastname: Meade
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Jingbo
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Andrés E
authors.initials: AE
authors.lastname: Dulcey
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Yang
authors.initials: Y
authors.lastname: Han
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Lihua
authors.initials: L
authors.lastname: Duan
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Steve
authors.initials: S
authors.lastname: Titus
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Melanie
authors.initials: M
authors.lastname: Bryant-Genevier
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Elena
authors.initials: E
authors.lastname: Barnaeva
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Marc
authors.initials: M
authors.lastname: Ferrer
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Javitch
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Thijs
authors.initials: T
authors.lastname: Beuming
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Noel T
authors.initials: NT
authors.lastname: Southall
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Marugan
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., L.S.C., A.E.M., B.N.M., T.B.D., J.L.C., A.P., J.A.M., D.R.S.); National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (J.X., X.H., A.E.D., S.T., M.B.-G., E.B., M.F., N.T.S., J.J.M.); Cellular, Molecular, Developmental Biology & Biophysics Program, Johns Hopkins University, Baltimore, Maryland (L.S.C.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, and Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York (Y.H., L.D., J.A.J.); Schrödinger Inc., New York, New York (T.B.); and Department of Physiology and Biophysics and Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, New York (L.S.).
authors.forename: David R
authors.initials: DR
authors.lastname: Sibley
mesh_terms: D000818:Animals; D019390:Arrestins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016466:CHO Cells; D002460:Cell Line; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D011485:Protein Binding / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D017448:Receptors, Dopamine D2; D054852:Small Molecule Libraries; D000071557:beta-Arrestins; D000242:Cyclic AMP; D019204:GTP-Binding Proteins
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