Structure-Based and Fragment-Based GPCR Drug Discovery

Conformation Guides Molecular Efficacy in Docking Screens of Activated β-2 Adrenergic G Protein Coupled Receptor

(2013) Dahlia R. Weiss et al.   ACS Chemical Biology

A Brief History of G-Protein Coupled Receptors (Nobel Lecture)

(2013) Robert J. Lefkowitz   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The Structural Basis of G-Protein-Coupled Receptor Signaling (Nobel Lecture)

(2013) Brian Kobilka   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Unlocking the secrets of the gatekeeper: Methods for stabilizing and crystallizing GPCRs

(2013) Nicolas Bertheleme et al.   BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

Surface plasmon resonance spectroscopy for characterisation of membrane protein–ligand interactions and its potential for drug discovery

(2013) Simon G. Patching   BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

Complementarity between in Silico and Biophysical Screening Approaches in Fragment-Based Lead Discovery against the A2A Adenosine Receptor

(2013) Dan Chen et al.   Journal of Chemical Information and Modeling

Biophysical Fragment Screening of the β1-Adrenergic Receptor: Identification of High Affinity Arylpiperazine Leads Using Structure-Based Drug Design

(2013) John A. Christopher et al.   JOURNAL OF MEDICINAL CHEMISTRY

Rational Design of Sulfonated A3 Adenosine Receptor-Selective Nucleosides as Pharmacological Tools To Study Chronic Neuropathic Pain

(2013) Silvia Paoletta et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure of class B GPCR corticotropin-releasing factor receptor 1

(2013) Kaspar Hollenstein et al.   NATURE

Structure of the human smoothened receptor bound to an antitumour agent

(2013) Chong Wang et al.   NATURE

Structure of the human glucagon class B G-protein-coupled receptor

(2013) Fai Yiu Siu et al.   NATURE

Molecular signatures of G-protein-coupled receptors

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

Adenosine receptors as drug targets — what are the challenges?

(2013) Jiang-Fan Chen et al.   NATURE REVIEWS DRUG DISCOVERY

Structure of the CCR5 Chemokine Receptor-HIV Entry Inhibitor Maraviroc Complex

(2013) Q. Tan et al.   SCIENCE

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

Discovery of β2 Adrenergic Receptor Ligands Using Biosensor Fragment Screening of Tagged Wild-Type Receptor

(2013) Tonia Aristotelous et al.   ACS Medicinal Chemistry Letters

Fragment Screening of GPCRs Using Biophysical Methods: Identification of Ligands of the Adenosine A2A Receptor with Novel Biological Activity

(2012) Dan Chen et al.   ACS Chemical Biology

Pyrazolo[1,5-c]quinazoline derivatives and their simplified analogues as adenosine receptor antagonists: Synthesis, structure–affinity relationships and molecular modeling studies

(2012) Daniela Catarzi et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Molecular modeling study of cyclic pentapeptide CXCR4 antagonists: New insight into CXCR4–FC131 interactions

(2012) Yasushi Yoshikawa et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Fragment Screening at Adenosine-A3 Receptors in Living Cells Using a Fluorescence-Based Binding Assay

(2012) Leigh A. Stoddart et al.   CHEMISTRY & BIOLOGY

Subtleties in GPCR drug discovery: a medicinal chemistry perspective

(2012) Masahiko Fujioka et al.   DRUG DISCOVERY TODAY

New chromene scaffolds for adenosine A2A receptors: Synthesis, pharmacology and structure–activity relationships

(2012) Filipe Areias et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Virtual Fragment Screening: Discovery of Histamine H3 Receptor Ligands Using Ligand-Based and Protein-Based Molecular Fingerprints

(2012) Francesco Sirci et al.   Journal of Chemical Information and Modeling

Ligand-, structure- and pharmacophore-based molecular fingerprints: a case study on adenosine A1, A2A, A2B, and A3 receptor antagonists

(2012) Francesco Sirci et al.   JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN

Rational Design of Conformationally Constrained Cyclopentapeptide Antagonists for C-X-C Chemokine Receptor 4 (CXCR4)

(2012) Jignesh Mungalpara et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Prospective Cross-Screening Study on G-Protein-Coupled Receptors: Lessons Learned in Virtual Compound Library Design

(2012) Marijn P. A. Sanders et al.   JOURNAL OF MEDICINAL CHEMISTRY

Design and Characterization of Optimized Adenosine A2A/A1 Receptor Antagonists for the Treatment of Parkinson's Disease

(2012) Brian C. Shook et al.   JOURNAL OF MEDICINAL CHEMISTRY

Optimization of Adenosine 5′-Carboxamide Derivatives as Adenosine Receptor Agonists Using Structure-Based Ligand Design and Fragment Screening

(2012) Dilip K. Tosh et al.   JOURNAL OF MEDICINAL CHEMISTRY

Identification of Novel Adenosine A2A Receptor Antagonists by Virtual Screening

(2012) Christopher J. Langmead et al.   JOURNAL OF MEDICINAL CHEMISTRY

Exploring the Directionality of 5-Substitutions in a New Series of 5-Alkylaminopyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine as a Strategy To Design Novel Human A3 Adenosine Receptor Antagonists.

(2012) Stephanie Federico et al.   JOURNAL OF MEDICINAL CHEMISTRY

Design of a Novel Cyclotide-Based CXCR4 Antagonist with Anti-Human Immunodeficiency Virus (HIV)-1 Activity

(2012) Teshome L. Aboye et al.   JOURNAL OF MEDICINAL CHEMISTRY

Molecular Determinants of Selectivity and Efficacy at the Dopamine D3 Receptor

(2012) Amy Hauck Newman et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of 1,2,4-Triazine Derivatives as Adenosine A2A Antagonists using Structure Based Drug Design

(2012) Miles Congreve et al.   JOURNAL OF MEDICINAL CHEMISTRY

Identifying Novel Adenosine Receptor Ligands by Simultaneous Proteochemometric Modeling of Rat and Human Bioactivity Data

(2012) Gerard J. P. van Westen et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Guided Design of A3 Adenosine Receptor-Selective Nucleosides: Combination of 2-Arylethynyl and Bicyclo[3.1.0]hexane Substitutions

(2012) Dilip K. Tosh et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure of the δ-opioid receptor bound to naltrindole

(2012) Sébastien Granier et al.   NATURE

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 nociceptin/orphanin FQ receptor in complex with a peptide mimetic

(2012) Aaron A. Thompson et al.   NATURE

Structure of the agonist-bound neurotensin receptor

(2012) Jim F. White et al.   NATURE

Crystal structure of the µ-opioid receptor bound to a morphinan antagonist

(2012) Aashish Manglik et al.   NATURE

Structure and dynamics of the M3 muscarinic acetylcholine receptor

(2012) Andrew C. Kruse et al.   NATURE

High-resolution crystal structure of human protease-activated receptor 1

(2012) Cheng Zhang et al.   NATURE

Vemurafenib: the first drug approved for BRAF-mutant cancer

(2012) Gideon Bollag et al.   NATURE REVIEWS DRUG DISCOVERY

Structure-based ligand discovery for the protein-protein interface of chemokine receptor CXCR4

(2012) M. M. Mysinger et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Crystal Structure of a Lipid G Protein-Coupled Receptor

(2012) M. A. Hanson et al.   SCIENCE

Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions

(2012) W. Liu et al.   SCIENCE

Fusion Partner Toolchest for the Stabilization and Crystallization of G Protein-Coupled Receptors

(2012) Eugene Chun et al.   STRUCTURE

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

(2012) Tony Warne et al.   STRUCTURE

A crystal clear solution for determining G-protein-coupled receptor structures

(2012) Christopher G. Tate   TRENDS IN BIOCHEMICAL SCIENCES

New insights from structural biology into the druggability of G protein-coupled receptors

(2012) Jonathan S. Mason et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

GPCR activation: a mutagenic spotlight on crystal structures

(2012) Edward C. Hulme   TRENDS IN PHARMACOLOGICAL SCIENCES

Stabilised G protein-coupled receptors in structure-based drug design: a case study with adenosine A2Areceptor

(2012) Stephen P. Andrews et al.   MedChemComm

Structure–Activity Relationships and Molecular Modeling of 1,2,4-Triazoles as Adenosine Receptor Antagonists

(2012) Jens Carlsson et al.   ACS Medicinal Chemistry Letters

Adenosine A2A Receptor Antagonists and Parkinson’s Disease

(2011) Brian C. Shook et al.   ACS Chemical Neuroscience

Fragment library screening reveals remarkable similarities between the G protein-coupled receptor histamine H4 and the ion channel serotonin 5-HT3A

(2011) Mark H.P. Verheij et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Biased signalling and allosteric machines: new vistas and challenges for drug discovery

(2011) Terry P Kenakin   BRITISH JOURNAL OF PHARMACOLOGY

Substructure-Based Virtual Screening for Adenosine A2A Receptor Ligands

(2011) Eelke van der Horst et al.   ChemMedChem

New 2-Heterocyclyl-imidazo[2,1-i]purin-5-one Derivatives as Potent and Selective Human A3Adenosine Receptor Antagonists

(2011) Pier Giovanni Baraldi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Evaluation of Molecular Modeling of Agonist Binding in Light of the Crystallographic Structure of an Agonist-Bound A2A Adenosine Receptor

(2011) Francesca Deflorian et al.   JOURNAL OF MEDICINAL CHEMISTRY

Biophysical Mapping of the Adenosine A2AReceptor

(2011) Andrei Zhukov et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Phosphoric Acid Mono-{2-[(E/Z)-4-(3,3-dimethyl-butyrylamino)-3,5-difluoro-benzoylimino]-thiazol-3-ylmethyl} Ester (Lu AA47070): A Phosphonooxymethylene Prodrug of a Potent and Selective hA2AReceptor Antagonist

(2011) Anette G. Sams et al.   JOURNAL OF MEDICINAL CHEMISTRY

Molecular Determinants of Ligand Binding Modes in the Histamine H4Receptor: Linking Ligand-Based Three-Dimensional Quantitative Structure–Activity Relationship (3D-QSAR) Models to in Silico Guided Receptor Mutagenesis Studies

(2011) Enade P. Istyastono et al.   JOURNAL OF MEDICINAL CHEMISTRY

Progress in Structure Based Drug Design for G Protein-Coupled Receptors

(2011) Miles Congreve et al.   JOURNAL OF MEDICINAL CHEMISTRY

Crystal Structure-Based Virtual Screening for Fragment-like Ligands of the Human Histamine H1Receptor

(2011) Chris de Graaf et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

(2011) Guillaume Lebon et al.   NATURE

Structure of the human histamine H1 receptor complex with doxepin

(2011) Tatsuro Shimamura 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

Crystal structure of the β2 adrenergic receptor–Gs protein complex

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

Ligand discovery from a dopamine D3 receptor homology model and crystal structure

(2011) Jens Carlsson et al.   Nature Chemical Biology

The Significance of G Protein-Coupled Receptor Crystallography for Drug Discovery

(2011) J. A. Salon et al.   PHARMACOLOGICAL REVIEWS

International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and Classification of Adenosine Receptors--An Update

(2011) B. B. Fredholm et al.   PHARMACOLOGICAL REVIEWS

The novel adenosine A2A antagonist Lu AA47070 reverses the motor and motivational effects produced by dopamine D2 receptor blockade

(2011) Lyndsey E. Collins et al.   PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR

Two distinct conformations of helix 6 observed in antagonist-bound structures of a  1-adrenergic receptor

(2011) R. Moukhametzianov 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

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

(2011) Andrew S. Doré et al.   STRUCTURE

Status of GPCR Modeling and Docking as Reflected by Community-wide GPCR Dock 2010 Assessment

(2011) Irina Kufareva et al.   STRUCTURE

Diversity and modularity of G protein-coupled receptor structures

(2011) Vsevolod Katritch et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Screening for GPCR Ligands Using Surface Plasmon Resonance

(2011) Iva Navratilova et al.   ACS Medicinal Chemistry Letters

Current perspectives on selective dopamine D3 receptor antagonists as pharmacotherapeutics for addictions and related disorders

(2010) Christian A. Heidbreder et al.   Annals of the New York Academy of Sciences

Recent developments in adenosine receptor ligands and their potential as novel drugs

(2010) Christa E. Müller et al.   BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

Molecular modeling study on potent and selective adenosine A3 receptor agonists

(2010) Diego Dal Ben et al.   BIOORGANIC & MEDICINAL CHEMISTRY

In silico directed chemical probing of the adenosine receptor family

(2010) Filipe M. Areias et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Adenosine Receptor Modeling: What Does the A2A Crystal Structure Tell Us?

(2010) D. Dal Ben et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

Preladenant, a selective A2A receptor antagonist, is active in primate models of movement disorders

(2010) Robert A. Hodgson et al.   EXPERIMENTAL NEUROLOGY

The Significance of 2-Furyl Ring Substitution with a 2-(para-substituted) Aryl Group in a New Series of Pyrazolo-triazolo-pyrimidines as Potent and Highly Selective hA3Adenosine Receptors Antagonists: New Insights into Structure−Affinity Relationship and Receptor−Antagonist Recognition

(2010) Siew Lee Cheong et al.   JOURNAL OF MEDICINAL CHEMISTRY

In Vivo Characterization of a Dual Adenosine A2A/A1Receptor Antagonist in Animal Models of Parkinson’s Disease

(2010) Brian C. Shook et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Based Discovery of Novel Chemotypes for Adenosine A2AReceptor Antagonists

(2010) Vsevolod Katritch et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Based Discovery of A2AAdenosine Receptor Ligands

(2010) Jens Carlsson et al.   JOURNAL OF MEDICINAL CHEMISTRY

Pyrimidine Derivatives as Potent and Selective A3Adenosine Receptor Antagonists

(2010) Vicente Yaziji et al.   JOURNAL OF MEDICINAL CHEMISTRY

Predicted 3D structures for adenosine receptors bound to ligands: Comparison to the crystal structure

(2010) William A. Goddard et al.   JOURNAL OF STRUCTURAL BIOLOGY

Conserved Binding Mode of Human β2Adrenergic Receptor Inverse Agonists and Antagonist Revealed by X-ray Crystallography

(2010) Daniel Wacker et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

The properties of thermostabilised G protein-coupled receptors (StaRs) and their use in drug discovery

(2010) Nathan Robertson et al.   NEUROPHARMACOLOGY

Structure based prediction of subtype-selectivity for adenosine receptor antagonists

(2010) Vsevolod Katritch et al.   NEUROPHARMACOLOGY

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

Discovery of highly potent and selective biphenylacylsulfonamide-based β3-adrenergic receptor agonists and molecular modeling based on the solved X-ray structure of the β2-adrenergic receptor: Part 6

(2009) Kouji Hattori et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Engineering G protein-coupled receptors to facilitate their structure determination

(2009) Christopher G Tate et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

Evaluation of Homology Modeling of G-Protein-Coupled Receptors in Light of the A2AAdenosine Receptor Crystallographic Structure

(2009) Andrei A. Ivanov et al.   JOURNAL OF MEDICINAL CHEMISTRY

2-Phenylpyrazolo[4,3-d]pyrimidin-7-one as a New Scaffold To Obtain Potent and Selective Human A3Adenosine Receptor Antagonists: New Insights into the Receptor−Antagonist Recognition†

(2009) Ombretta Lenzi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Modern Homology Modeling of G-Protein Coupled Receptors: Which Structural Template to Use?

(2009) Juan Carlos Mobarec et al.   JOURNAL OF MEDICINAL CHEMISTRY

Thermostabilization of the Neurotensin Receptor NTS1

(2009) Yoko Shibata et al.   JOURNAL OF MOLECULAR BIOLOGY

The structure and function of G-protein-coupled receptors

(2009) Daniel M. Rosenbaum et al.   NATURE

Community-wide assessment of GPCR structure modelling and ligand docking: GPCR Dock 2008

(2009) Mayako Michino et al.   NATURE REVIEWS DRUG DISCOVERY

Adenosine, adenosine A2A antagonists, and Parkinson's disease

(2009) P. Jenner et al.   PARKINSONISM & RELATED DISORDERS

Structure-based discovery of  2-adrenergic receptor ligands

(2009) P. Kolb et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

GPCR 3D homology models for ligand screening: Lessons learned from blind predictions of adenosine A2a receptor complex

(2009) Vsevolod Katritch et al.   PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS

Use of the X-ray structure of the Beta2-adrenergic receptor for drug discovery

(2008) Sid Topiol et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Use of the X-ray structure of the β2-adrenergic receptor for drug discovery. Part 2: Identification of active compounds

(2008) Michael Sabio et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Recent Developments in Fragment-Based Drug Discovery

(2008) Miles Congreve et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Novel Human Histamine H4 Receptor Ligands by Large-Scale Structure-Based Virtual Screening

(2008) Róbert Kiss et al.   JOURNAL OF MEDICINAL CHEMISTRY

Selective Structure-Based Virtual Screening for Full and Partial Agonists of the β2 Adrenergic Receptor

(2008) Chris de Graaf et al.   JOURNAL OF MEDICINAL 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

Co-evolving stability and conformational homogeneity of the human adenosine A2a receptor

(2008) F. Magnani et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Conformational thermostabilization of the  1-adrenergic receptor in a detergent-resistant form

(2008) M. J. Serrano-Vega et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity

(2008) J. Tsai 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

A Specific Cholesterol Binding Site Is Established by the 2.8 Å Structure of the Human β2-Adrenergic Receptor

(2008) Michael A. Hanson et al.   STRUCTURE