Biased Agonism at G Protein-Coupled Receptors: The Promise and the Challenges-A Medicinal Chemistry Perspective

Impact of Clinically Relevant Mutations on the Pharmacoregulation and Signaling Bias of the Calcium-Sensing Receptor by Positive and Negative Allosteric Modulators

(2013) Katie Leach et al.   ENDOCRINOLOGY

A Structure–Activity Analysis of Biased Agonism at the Dopamine D2 Receptor

(2013) Jeremy Shonberg et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure–Activity Relationships and Discovery of a G Protein Biased μ Opioid Receptor Ligand, [(3-Methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro-[4.5]decan-9-yl]ethyl})amine (TRV130), for the Treatment of Acute Severe Pain

(2013) Xiao-Tao Chen et al.   JOURNAL OF MEDICINAL CHEMISTRY

Activation and allosteric modulation of a muscarinic acetylcholine receptor

(2013) Andrew C. Kruse et al.   NATURE

Molecular signatures of G-protein-coupled receptors

(2013) A. J. Venkatakrishnan et al.   NATURE

Signalling bias in new drug discovery: detection, quantification and therapeutic impact

(2013) Terry Kenakin et al.   NATURE REVIEWS DRUG DISCOVERY

Measurements of ligand bias and functional affinity

(2013) Terry Kenakin et al.   NATURE REVIEWS DRUG DISCOVERY

Quantifying biased agonism: understanding the links between affinity and efficacy

(2013) Sudarshan Rajagopal   NATURE REVIEWS DRUG DISCOVERY

Structural Basis for Molecular Recognition at Serotonin Receptors

(2013) C. Wang et al.   SCIENCE

Structural Features for Functional Selectivity at Serotonin Receptors

(2013) D. Wacker et al.   SCIENCE

Structure-Function of the G Protein–Coupled Receptor Superfamily

(2012) Vsevolod Katritch et al.   Annual Review of Pharmacology and Toxicology

Functional efficacy of adenosine A2A receptor agonists is positively correlated to their receptor residence time

(2012) Dong Guo et al.   BRITISH JOURNAL OF PHARMACOLOGY

Probing Heterotrimeric G Protein Activation: Applications to Biased Ligands

(2012) Colette Denis et al.   CURRENT PHARMACEUTICAL DESIGN

Identification of Molecular Phenotypes and Biased Signaling Induced by Naturally Occurring Mutations of the Human Calcium-Sensing Receptor

(2012) Katie Leach et al.   ENDOCRINOLOGY

Stimulus Bias Provides Evidence for Conformational Constraints in the Structure of a G Protein-coupled Receptor

(2012) Karen J. Gregory et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Structure–Functional Selectivity Relationship Studies of β-Arrestin-Biased Dopamine D2 Receptor Agonists

(2012) Xin Chen et al.   JOURNAL OF MEDICINAL CHEMISTRY

Biased Agonism at the Parathyroid Hormone Receptor: A Demonstration of Functional Selectivity in Bone Metabolism

(2012) B. N. Bohinc et al.   MINI-REVIEWS IN MEDICINAL CHEMISTRY

Gonadotropin-Releasing Hormone Receptor Signaling: Biased and Unbiased

(2012) C. A. McArdle   MINI-REVIEWS IN MEDICINAL CHEMISTRY

Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist

(2012) Kazuko Haga et al.   NATURE

Structure of the human κ-opioid receptor in complex with JDTic

(2012) Huixian Wu et al.   NATURE

Structure of the agonist-bound neurotensin receptor

(2012) Jim F. White et al.   NATURE

Deciphering biased-agonism complexity reveals a new active AT1 receptor entity

(2012) Aude Saulière et al.   Nature Chemical Biology

Advancing schizophrenia drug discovery: optimizing rodent models to bridge the translational gap

(2012) Judith Pratt et al.   NATURE REVIEWS DRUG DISCOVERY

The GPCR Network: a large-scale collaboration to determine human GPCR structure and function

(2012) Raymond C. Stevens et al.   NATURE REVIEWS DRUG DISCOVERY

Impedance Responses Reveal β2-Adrenergic Receptor Signaling Pluridimensionality and Allow Classification of Ligands with Distinct Signaling Profiles

(2012) Wayne Stallaert et al.   PLoS One

Structural insights into biased G protein-coupled receptor signaling revealed by fluorescence spectroscopy

(2012) R. Rahmeh et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Functional selectivity of adenosine A1 receptor ligands?

(2012) Ellen V. Langemeijer et al.   Purinergic Signalling

Biased Signaling Pathways in  2-Adrenergic Receptor Characterized by 19F-NMR

(2012) J. J. Liu et al.   SCIENCE

Crystal Structures of a Stabilized β1-Adrenoceptor Bound to the Biased Agonists Bucindolol and Carvedilol

(2012) Tony Warne et al.   STRUCTURE

Bridging the gap: bitopic ligands of G-protein-coupled receptors

(2012) J. Robert Lane et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

A Simple Method for Quantifying Functional Selectivity and Agonist Bias

(2011) Terry Kenakin et al.   ACS Chemical Neuroscience

Strategies to Discover Unexpected Targets for Drugs Active at G Protein–Coupled Receptors

(2011) John A. Allen et al.   Annual Review of Pharmacology and Toxicology

The Best of Both Worlds? Bitopic Orthosteric/Allosteric Ligands of G Protein–Coupled Receptors

(2011) Celine Valant et al.   Annual Review of Pharmacology and Toxicology

Structural insights into agonist-induced activation of G-protein-coupled receptors

(2011) Xavier Deupi et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

Positive and Negative Allosteric Modulators Promote Biased Signaling at the Calcium-Sensing Receptor

(2011) Anna E. Davey et al.   ENDOCRINOLOGY

Ligand functional selectivity and quantitative pharmacology at G protein-coupled receptors

(2011) Wayne Stallaert et al.   Expert Opinion on Drug Discovery

Highly Potent 5-Aminotetrahydropyrazolopyridines: Enantioselective Dopamine D3Receptor Binding, Functional Selectivity, and Analysis of Receptor−Ligand Interactions

(2011) Nuska Tschammer et al.   JOURNAL OF MEDICINAL CHEMISTRY

Quantifying Ligand Bias at Seven-Transmembrane Receptors

(2011) S. Rajagopal et al.   MOLECULAR PHARMACOLOGY

Agonist-bound adenosine A2A receptor structures reveal common features of GPCR activation

(2011) Guillaume Lebon et al.   NATURE

Crystal structure of metarhodopsin II

(2011) Hui-Woog Choe et al.   NATURE

The structural basis of agonist-induced activation in constitutively active rhodopsin

(2011) Jörg Standfuss et al.   NATURE

The structural basis for agonist and partial agonist action on a β1-adrenergic receptor

(2011) Tony Warne et al.   NATURE

Structure of a nanobody-stabilized active state of the β2 adrenoceptor

(2011) Søren G. F. Rasmussen et al.   NATURE

Structure and function of an irreversible agonist-β2 adrenoceptor complex

(2011) Daniel M. Rosenbaum et al.   NATURE

Crystal structure of the β2 adrenergic receptor–Gs protein complex

(2011) Søren G. F. Rasmussen et al.   NATURE

Multiple ligand-specific conformations of the β2-adrenergic receptor

(2011) Alem W Kahsai et al.   Nature Chemical Biology

Inactive-state preassembly of Gq-coupled receptors and Gq heterotrimers

(2011) Kou Qin et al.   Nature Chemical Biology

Activation mechanism of the  2-adrenergic receptor

(2011) R. O. Dror et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Discovery of  -Arrestin-Biased Dopamine D2 Ligands for Probing Signal Transduction Pathways Essential for Antipsychotic Efficacy

(2011) J. A. Allen et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Structure of an Agonist-Bound Human A2A Adenosine Receptor

(2011) F. Xu et al.   SCIENCE

Distinct Phosphorylation Sites on the  2-Adrenergic Receptor Establish a Barcode That Encodes Differential Functions of  -Arrestin

(2011) K. N. Nobles et al.   Science Signaling

Structure of the Adenosine A2A Receptor in Complex with ZM241385 and the Xanthines XAC and Caffeine

(2011) Andrew S. Doré et al.   STRUCTURE

Ligand-Dependent Perturbation of the Conformational Ensemble for the GPCR β2 Adrenergic Receptor Revealed by HDX

(2011) Graham M. West et al.   STRUCTURE

Emerging paradigms of β-arrestin-dependent seven transmembrane receptor signaling

(2011) Arun K. Shukla et al.   TRENDS IN BIOCHEMICAL SCIENCES

Dynamics of the β2-Adrenergic G-Protein Coupled Receptor Revealed by Hydrogen−Deuterium Exchange

(2010) Xi Zhang et al.   ANALYTICAL CHEMISTRY

Conformational Changes in the G Protein-Coupled Receptor Rhodopsin Revealed by Histidine Hydrogen−Deuterium Exchange

(2010) David T. Lodowski et al.   BIOCHEMISTRY

An operational model of pharmacological agonism: the effect of E/[A] curve shape on agonist dissociation constant estimation

(2010) JW Black et al.   BRITISH JOURNAL OF PHARMACOLOGY

Rational design of dualsteric GPCR ligands: quests and promise

(2010) Klaus Mohr et al.   BRITISH JOURNAL OF PHARMACOLOGY

Differential G-protein-coupled Receptor Phosphorylation Provides Evidence for a Signaling Bar Code

(2010) Adrian J. Butcher et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Identification of Orthosteric and Allosteric Site Mutations in M2Muscarinic Acetylcholine Receptors That Contribute to Ligand-selective Signaling Bias

(2010) Karen J. Gregory et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Hybrid Ortho/Allosteric Ligands for the Adenosine A1Receptor

(2010) Rajeshwar Narlawar et al.   JOURNAL OF MEDICINAL CHEMISTRY

Functional Selectivity and Biased Receptor Signaling

(2010) T. Kenakin   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Selectively Engaging  -Arrestins at the Angiotensin II Type 1 Receptor Reduces Blood Pressure and Increases Cardiac Performance

(2010) J. D. Violin et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Agonist-Biased Signaling at the Histamine H4 Receptor: JNJ7777120 Recruits  -Arrestin without Activating G Proteins

(2010) E. M. Rosethorne et al.   MOLECULAR PHARMACOLOGY

Histidine 6.55 Is a Major Determinant of Ligand-Biased Signaling in Dopamine D2L Receptor

(2010) N. Tschammer et al.   MOLECULAR PHARMACOLOGY

H2 Relaxin Is a Biased Ligand Relative to H3 Relaxin at the Relaxin Family Peptide Receptor 3 (RXFP3)

(2010) E. T. van der Westhuizen et al.   MOLECULAR PHARMACOLOGY

Allosteric Ligands of the Glucagon-Like Peptide 1 Receptor (GLP-1R) Differentially Modulate Endogenous and Exogenous Peptide Responses in a Pathway-Selective Manner: Implications for Drug Screening

(2010) C. Koole et al.   MOLECULAR PHARMACOLOGY

Quantification of Functional Selectivity at the Human  1A-Adrenoceptor

(2010) B. A. Evans et al.   MOLECULAR PHARMACOLOGY

Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor

(2010) Michael P. Bokoch et al.   NATURE

Deconvolution of complex G protein–coupled receptor signaling in live cells using dynamic mass redistribution measurements

(2010) Ralf Schröder et al.   NATURE BIOTECHNOLOGY

Allosteric modulation of G protein-coupled receptors: A pharmacological perspective

(2010) Peter Keov et al.   NEUROPHARMACOLOGY

Energy Landscapes as a Tool to Integrate GPCR Structure, Dynamics, and Function

(2010) Xavier Deupi et al.   PHYSIOLOGY

Structures of the CXCR4 Chemokine GPCR with Small-Molecule and Cyclic Peptide Antagonists

(2010) B. Wu et al.   SCIENCE

Structure of the Human Dopamine D3 Receptor in Complex with a D2/D3 Selective Antagonist

(2010) E. Y. T. Chien et al.   SCIENCE

Signal transduction and functional selectivity of F15599, a preferential post-synaptic 5-HT1Areceptor agonist

(2009) A Newman-Tancredi et al.   BRITISH JOURNAL OF PHARMACOLOGY

The role of histamine H4 receptor in immune and inflammatory disorders

(2009) E Zampeli et al.   BRITISH JOURNAL OF PHARMACOLOGY

Location of the Retinal Chromophore in the Activated State of Rhodopsin*

(2009) Shivani Ahuja et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Independent β-Arrestin2 and Gq/Protein Kinase Cζ Pathways for ERK Stimulated by Angiotensin Type 1A Receptors in Vascular Smooth Muscle Cells Converge on Transactivation of the Epidermal Growth Factor Receptor

(2009) Jihee Kim et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

β-Arrestin1 mediates nicotinic acid–induced flushing, but not its antilipolytic effect, in mice

(2009) Robert W. Walters et al.   JOURNAL OF CLINICAL INVESTIGATION

An optical dynamic mass redistribution assay reveals biased signaling of dualsteric GPCR activators

(2009) Anna Kebig et al.   JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION

Orthosteric/Allosteric Bitopic Ligands: Going Hybrid at GPCRs

(2009) C. Valant et al.   MOLECULAR INTERVENTIONS

Exploring the Mechanism of Agonist Efficacy: A Relationship between Efficacy and Agonist Dissociation Rate at the Muscarinic M3 Receptor

(2009) D. A. Sykes et al.   MOLECULAR PHARMACOLOGY

The structure and function of G-protein-coupled receptors

(2009) Daniel M. Rosenbaum et al.   NATURE

Agonist binding, agonist affinity and agonist efficacy at G protein-coupled receptors

(2008) P G Strange   BRITISH JOURNAL OF PHARMACOLOGY

Dualsteric GPCR targeting: a novel route to binding and signaling pathway selectivity

(2008) Johannes Antony et al.   FASEB JOURNAL

A Novel Mechanism of G Protein-coupled Receptor Functional Selectivity

(2008) Celine Valant et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Structure of a β1-adrenergic G-protein-coupled receptor

(2008) Tony Warne et al.   NATURE

Structural diversity of G protein-coupled receptors and significance for drug discovery

(2008) Malin C. Lagerström et al.   NATURE REVIEWS DRUG DISCOVERY

On the analysis of ligand-directed signaling at G protein-coupled receptors

(2008) Frederick J. Ehlert   NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY

High-resolution distance mapping in rhodopsin reveals the pattern of helix movement due to activation

(2008) C. Altenbach et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Antagonism of dopamine D2 receptor/ -arrestin 2 interaction is a common property of clinically effective antipsychotics

(2008) B. Masri et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The 2.6 Angstrom Crystal Structure of a Human A2A Adenosine Receptor Bound to an Antagonist

(2008) V.-P. Jaakola et al.   SCIENCE

Location, location, location…site-specific GPCR phosphorylation offers a mechanism for cell-type-specific signalling

(2008) Andrew B. Tobin et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Activation of G Protein–Coupled Receptors: Beyond Two-State Models and Tertiary Conformational Changes

(2007) Paul S.-H. Park et al.   Annual Review of Pharmacology and Toxicology