title: Chemical switch of a metabotropic glutamate receptor 2 silent allosteric modulator into dual metabotropic glutamate receptor 2/3 negative/positive allosteric modulators.
abstract: Using an mGluR2 FRET-based binding assay, binders of the transmembrane region devoid of functional activity were identified. It is reported that slight chemical modifications of these SAMs can dramatically change activity of the resulting analogues without altering their affinities. Starting from compound 1, three mGluR2 NAMs showing also mGluR3 PAM activities were obtained. SAMs therefore represent a useful approach to explore the chemical space for GPCR allosteric modulator identification.
authors.affiliation: Domain Therapeutics SA, Bioparc, Boulevard Sebastien Brant, F-67400 Strasbourg-Illkirch, France. sschann@domaintherapeutics
authors.forename: Stephan
authors.initials: S
authors.lastname: Schann
authors.forename: Stanislas
authors.initials: S
authors.lastname: Mayer
authors.forename: Christel
authors.initials: C
authors.lastname: Franchet
authors.forename: Mélanie
authors.initials: M
authors.lastname: Frauli
authors.forename: Edith
authors.initials: E
authors.lastname: Steinberg
authors.forename: Mireille
authors.initials: M
authors.lastname: Thomas
authors.forename: Luc
authors.initials: L
authors.lastname: Baron
authors.forename: Pascal
authors.initials: P
authors.lastname: Neuville
mesh_terms: D000494:Allosteric Regulation; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D018683:Excitatory Amino Acid Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D031541:Fluorescence Resonance Energy Transfer; D057166:High-Throughput Screening Assays; D006801:Humans; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship
chemical_list: D001578:Benzopyrans; D018683:Excitatory Amino Acid Agents; D018094:Receptors, Metabotropic Glutamate; D054852:Small Molecule Libraries; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D002118:Calcium