title: International Union of Basic and Clinical Pharmacology. XC. multisite pharmacology: recommendations for the nomenclature of receptor allosterism and allosteric ligands.
abstract: Allosteric interactions play vital roles in metabolic processes and signal transduction and, more recently, have become the focus of numerous pharmacological studies because of the potential for discovering more target-selective chemical probes and therapeutic agents. In addition to classic early studies on enzymes, there are now examples of small molecule allosteric modulators for all superfamilies of receptors encoded by the genome, including ligand- and voltage-gated ion channels, G protein-coupled receptors, nuclear hormone receptors, and receptor tyrosine kinases. As a consequence, a vast array of pharmacologic behaviors has been ascribed to allosteric ligands that can vary in a target-, ligand-, and cell-/tissue-dependent manner. The current article presents an overview of allostery as applied to receptor families and approaches for detecting and validating allosteric interactions and gives recommendations for the nomenclature of allosteric ligands and their properties.
authors.affiliation: Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (A.C., P.M.S., C.J.L.); Collège de France and CNRS URA 2182, Institut Pasteur, Paris, France (J.-P.C.); Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington (W.A.C.); PIQUR Therapeutics AG, Basel, Switzerland (D.F.); Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, Louisiana (T.P.B.); Signal Transduction Laboratory, Molecular Endocrinology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina (J.A.C.); Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California (R.W.O.); Division of Neuroscience, School of Medicine, University of Dundee, Scotland, United Kingdom (J.A.P.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan (R.R.N.); Institut de Genomique Fonctionelle, CNRS, Montpellier, France (J.-P.P.); Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina (T.P.K.); Department of Pharmacology, University of California, Irvine, California (F.J.E.); and Research Solutions SARL, Paris, France (M.S.) arthur.christopoulos@monash.edu.
authors.forename: Arthur
authors.initials: A
authors.lastname: Christopoulos
authors.affiliation: Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (A.C., P.M.S., C.J.L.); Collège de France and CNRS URA 2182, Institut Pasteur, Paris, France (J.-P.C.); Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington (W.A.C.); PIQUR Therapeutics AG, Basel, Switzerland (D.F.); Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, Louisiana (T.P.B.); Signal Transduction Laboratory, Molecular Endocrinology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina (J.A.C.); Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California (R.W.O.); Division of Neuroscience, School of Medicine, University of Dundee, Scotland, United Kingdom (J.A.P.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan (R.R.N.); Institut de Genomique Fonctionelle, CNRS, Montpellier, France (J.-P.P.); Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina (T.P.K.); Department of Pharmacology, University of California, Irvine, California (F.J.E.); and Research Solutions SARL, Paris, France (M.S.).
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Changeux
authors.affiliation: Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (A.C., P.M.S., C.J.L.); Collège de France and CNRS URA 2182, Institut Pasteur, Paris, France (J.-P.C.); Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington (W.A.C.); PIQUR Therapeutics AG, Basel, Switzerland (D.F.); Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, Louisiana (T.P.B.); Signal Transduction Laboratory, Molecular Endocrinology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina (J.A.C.); Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California (R.W.O.); Division of Neuroscience, School of Medicine, University of Dundee, Scotland, United Kingdom (J.A.P.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan (R.R.N.); Institut de Genomique Fonctionelle, CNRS, Montpellier, France (J.-P.P.); Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina (T.P.K.); Department of Pharmacology, University of California, Irvine, California (F.J.E.); and Research Solutions SARL, Paris, France (M.S.).
authors.forename: William A
authors.initials: WA
authors.lastname: Catterall
authors.affiliation: Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (A.C., P.M.S., C.J.L.); Collège de France and CNRS URA 2182, Institut Pasteur, Paris, France (J.-P.C.); Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington (W.A.C.); PIQUR Therapeutics AG, Basel, Switzerland (D.F.); Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, Louisiana (T.P.B.); Signal Transduction Laboratory, Molecular Endocrinology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina (J.A.C.); Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California (R.W.O.); Division of Neuroscience, School of Medicine, University of Dundee, Scotland, United Kingdom (J.A.P.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan (R.R.N.); Institut de Genomique Fonctionelle, CNRS, Montpellier, France (J.-P.P.); Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina (T.P.K.); Department of Pharmacology, University of California, Irvine, California (F.J.E.); and Research Solutions SARL, Paris, France (M.S.).
authors.forename: Doriano
authors.initials: D
authors.lastname: Fabbro
authors.affiliation: Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (A.C., P.M.S., C.J.L.); Collège de France and CNRS URA 2182, Institut Pasteur, Paris, France (J.-P.C.); Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington (W.A.C.); PIQUR Therapeutics AG, Basel, Switzerland (D.F.); Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, Louisiana (T.P.B.); Signal Transduction Laboratory, Molecular Endocrinology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina (J.A.C.); Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California (R.W.O.); Division of Neuroscience, School of Medicine, University of Dundee, Scotland, United Kingdom (J.A.P.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan (R.R.N.); Institut de Genomique Fonctionelle, CNRS, Montpellier, France (J.-P.P.); Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina (T.P.K.); Department of Pharmacology, University of California, Irvine, California (F.J.E.); and Research Solutions SARL, Paris, France (M.S.).
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Burris
authors.affiliation: Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (A.C., P.M.S., C.J.L.); Collège de France and CNRS URA 2182, Institut Pasteur, Paris, France (J.-P.C.); Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington (W.A.C.); PIQUR Therapeutics AG, Basel, Switzerland (D.F.); Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, Louisiana (T.P.B.); Signal Transduction Laboratory, Molecular Endocrinology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina (J.A.C.); Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California (R.W.O.); Division of Neuroscience, School of Medicine, University of Dundee, Scotland, United Kingdom (J.A.P.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan (R.R.N.); Institut de Genomique Fonctionelle, CNRS, Montpellier, France (J.-P.P.); Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina (T.P.K.); Department of Pharmacology, University of California, Irvine, California (F.J.E.); and Research Solutions SARL, Paris, France (M.S.).
authors.forename: John A
authors.initials: JA
authors.lastname: Cidlowski
authors.affiliation: Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (A.C., P.M.S., C.J.L.); Collège de France and CNRS URA 2182, Institut Pasteur, Paris, France (J.-P.C.); Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington (W.A.C.); PIQUR Therapeutics AG, Basel, Switzerland (D.F.); Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, Louisiana (T.P.B.); Signal Transduction Laboratory, Molecular Endocrinology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina (J.A.C.); Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California (R.W.O.); Division of Neuroscience, School of Medicine, University of Dundee, Scotland, United Kingdom (J.A.P.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan (R.R.N.); Institut de Genomique Fonctionelle, CNRS, Montpellier, France (J.-P.P.); Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina (T.P.K.); Department of Pharmacology, University of California, Irvine, California (F.J.E.); and Research Solutions SARL, Paris, France (M.S.).
authors.forename: Richard W
authors.initials: RW
authors.lastname: Olsen
authors.affiliation: Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (A.C., P.M.S., C.J.L.); Collège de France and CNRS URA 2182, Institut Pasteur, Paris, France (J.-P.C.); Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington (W.A.C.); PIQUR Therapeutics AG, Basel, Switzerland (D.F.); Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, Louisiana (T.P.B.); Signal Transduction Laboratory, Molecular Endocrinology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina (J.A.C.); Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California (R.W.O.); Division of Neuroscience, School of Medicine, University of Dundee, Scotland, United Kingdom (J.A.P.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan (R.R.N.); Institut de Genomique Fonctionelle, CNRS, Montpellier, France (J.-P.P.); Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina (T.P.K.); Department of Pharmacology, University of California, Irvine, California (F.J.E.); and Research Solutions SARL, Paris, France (M.S.).
authors.forename: John A
authors.initials: JA
authors.lastname: Peters
authors.affiliation: Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (A.C., P.M.S., C.J.L.); Collège de France and CNRS URA 2182, Institut Pasteur, Paris, France (J.-P.C.); Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington (W.A.C.); PIQUR Therapeutics AG, Basel, Switzerland (D.F.); Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, Louisiana (T.P.B.); Signal Transduction Laboratory, Molecular Endocrinology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina (J.A.C.); Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California (R.W.O.); Division of Neuroscience, School of Medicine, University of Dundee, Scotland, United Kingdom (J.A.P.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan (R.R.N.); Institut de Genomique Fonctionelle, CNRS, Montpellier, France (J.-P.P.); Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina (T.P.K.); Department of Pharmacology, University of California, Irvine, California (F.J.E.); and Research Solutions SARL, Paris, France (M.S.).
authors.forename: Richard R
authors.initials: RR
authors.lastname: Neubig
authors.affiliation: Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (A.C., P.M.S., C.J.L.); Collège de France and CNRS URA 2182, Institut Pasteur, Paris, France (J.-P.C.); Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington (W.A.C.); PIQUR Therapeutics AG, Basel, Switzerland (D.F.); Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, Louisiana (T.P.B.); Signal Transduction Laboratory, Molecular Endocrinology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina (J.A.C.); Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California (R.W.O.); Division of Neuroscience, School of Medicine, University of Dundee, Scotland, United Kingdom (J.A.P.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan (R.R.N.); Institut de Genomique Fonctionelle, CNRS, Montpellier, France (J.-P.P.); Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina (T.P.K.); Department of Pharmacology, University of California, Irvine, California (F.J.E.); and Research Solutions SARL, Paris, France (M.S.).
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Pin
authors.affiliation: Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (A.C., P.M.S., C.J.L.); Collège de France and CNRS URA 2182, Institut Pasteur, Paris, France (J.-P.C.); Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington (W.A.C.); PIQUR Therapeutics AG, Basel, Switzerland (D.F.); Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, Louisiana (T.P.B.); Signal Transduction Laboratory, Molecular Endocrinology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina (J.A.C.); Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California (R.W.O.); Division of Neuroscience, School of Medicine, University of Dundee, Scotland, United Kingdom (J.A.P.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan (R.R.N.); Institut de Genomique Fonctionelle, CNRS, Montpellier, France (J.-P.P.); Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina (T.P.K.); Department of Pharmacology, University of California, Irvine, California (F.J.E.); and Research Solutions SARL, Paris, France (M.S.).
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Sexton
authors.affiliation: Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (A.C., P.M.S., C.J.L.); Collège de France and CNRS URA 2182, Institut Pasteur, Paris, France (J.-P.C.); Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington (W.A.C.); PIQUR Therapeutics AG, Basel, Switzerland (D.F.); Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, Louisiana (T.P.B.); Signal Transduction Laboratory, Molecular Endocrinology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina (J.A.C.); Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California (R.W.O.); Division of Neuroscience, School of Medicine, University of Dundee, Scotland, United Kingdom (J.A.P.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan (R.R.N.); Institut de Genomique Fonctionelle, CNRS, Montpellier, France (J.-P.P.); Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina (T.P.K.); Department of Pharmacology, University of California, Irvine, California (F.J.E.); and Research Solutions SARL, Paris, France (M.S.).
authors.forename: Terry P
authors.initials: TP
authors.lastname: Kenakin
authors.affiliation: Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (A.C., P.M.S., C.J.L.); Collège de France and CNRS URA 2182, Institut Pasteur, Paris, France (J.-P.C.); Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington (W.A.C.); PIQUR Therapeutics AG, Basel, Switzerland (D.F.); Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, Louisiana (T.P.B.); Signal Transduction Laboratory, Molecular Endocrinology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina (J.A.C.); Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California (R.W.O.); Division of Neuroscience, School of Medicine, University of Dundee, Scotland, United Kingdom (J.A.P.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan (R.R.N.); Institut de Genomique Fonctionelle, CNRS, Montpellier, France (J.-P.P.); Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina (T.P.K.); Department of Pharmacology, University of California, Irvine, California (F.J.E.); and Research Solutions SARL, Paris, France (M.S.).
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Ehlert
authors.affiliation: Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (A.C., P.M.S., C.J.L.); Collège de France and CNRS URA 2182, Institut Pasteur, Paris, France (J.-P.C.); Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington (W.A.C.); PIQUR Therapeutics AG, Basel, Switzerland (D.F.); Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, Louisiana (T.P.B.); Signal Transduction Laboratory, Molecular Endocrinology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina (J.A.C.); Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California (R.W.O.); Division of Neuroscience, School of Medicine, University of Dundee, Scotland, United Kingdom (J.A.P.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan (R.R.N.); Institut de Genomique Fonctionelle, CNRS, Montpellier, France (J.-P.P.); Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina (T.P.K.); Department of Pharmacology, University of California, Irvine, California (F.J.E.); and Research Solutions SARL, Paris, France (M.S.).
authors.forename: Michael
authors.initials: M
authors.lastname: Spedding
authors.affiliation: Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (A.C., P.M.S., C.J.L.); Collège de France and CNRS URA 2182, Institut Pasteur, Paris, France (J.-P.C.); Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington (W.A.C.); PIQUR Therapeutics AG, Basel, Switzerland (D.F.); Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, Louisiana (T.P.B.); Signal Transduction Laboratory, Molecular Endocrinology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina (J.A.C.); Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California (R.W.O.); Division of Neuroscience, School of Medicine, University of Dundee, Scotland, United Kingdom (J.A.P.); Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan (R.R.N.); Institut de Genomique Fonctionelle, CNRS, Montpellier, France (J.-P.P.); Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina (T.P.K.); Department of Pharmacology, University of California, Irvine, California (F.J.E.); and Research Solutions SARL, Paris, France (M.S.).
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Langmead
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008024:Ligands; D008956:Models, Chemical; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism; D009626:Terminology as Topic
chemical_list: D007473:Ion Channels; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D043562:Receptors, G-Protein-Coupled; D011505:Protein-Tyrosine Kinases