title: Co-operative binding assay for the characterization of mGlu4 allosteric modulators.
abstract: The interest in the role of metabotropic glutamate receptor 4 (mGlu4) in CNS related disorders has increased the need for methods to investigate the binding of allosteric drug candidates. Our aim is to present the first fully characterized in vitro binding assay of mGlu4 positive allosteric modulators (PAMs). Results suggest that mGlu4 PAMs have characteristic co-operative binding with orthosteric glutamate, which offers a notable insight to the further development of mGlu4 targeted therapies.
authors.affiliation: Athinoula A. Martinos Biomedical Imaging Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Pekka
authors.initials: P
authors.lastname: Poutiainen
authors.affiliation: Athinoula A. Martinos Biomedical Imaging Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Kun-Eek
authors.initials: KE
authors.lastname: Kil
authors.affiliation: Athinoula A. Martinos Biomedical Imaging Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Zhaoda
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Darshini
authors.initials: D
authors.lastname: Kuruppu
authors.affiliation: Experimental Therapeutics and Molecular Imaging Laboratory, Neuroscience Center, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Program in Neuroscience, Harvard Medical School, Boston, MA, USA.
authors.forename: Bakhos
authors.initials: B
authors.lastname: Tannous
authors.affiliation: Athinoula A. Martinos Biomedical Imaging Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: abrownell@partners.org.
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Brownell
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D018683:Excitatory Amino Acid Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
chemical_list: D018683:Excitatory Amino Acid Agents; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; C108823:metabotropic glutamate receptor 4
keywords: Binding affinity; Metabotropic glutamate receptor; Parkinson disease; mGlu(4)