title: New ligands at the melatonin binding site MT(3).
abstract: The third melatonin binding site, MT3 is a non-classical one since it is not a seven transmembrane domains receptor, but an enzyme, quinone reductase 2. A major concern for the study of the physiological role of this site is the lack of specific ligands, permitting to more accurately dissect the pathways linked to the activation of MT3. Indeed, in the course of finding new ligands, we identified a new series of compounds with affinity to the binding site in the nM range, particularly 2,3-dimethoxy 7-hydroxy 10-methyl 5H 10H indeno(1,2-b)indol-10-one (DMHMIO), with a Ki of 190 pM. Based on slightly different and novel synthons compared to most of the compounds used in melatonin pharmacology studies, these compounds offer new perspective for the description of the melatonin pathways, so much more by not having any affinity towards the MT1 and MT2 'classical' melatonin receptors.
authors.affiliation: Division de Chimie médicinale E, Institut de Recherches SERVIER, Suresnes, France.
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Boussard
authors.forename: Sandrine
authors.initials: S
authors.lastname: Truche
authors.forename: Anne
authors.initials: A
authors.lastname: Rousseau-Rojas
authors.forename: Sylvie
authors.initials: S
authors.lastname: Briss
authors.forename: Sophie
authors.initials: S
authors.lastname: Descamps
authors.forename: Monique
authors.initials: M
authors.lastname: Droual
authors.forename: Michel
authors.initials: M
authors.lastname: Wierzbicki
authors.forename: Gilles
authors.initials: G
authors.lastname: Ferry
authors.forename: Valérie
authors.initials: V
authors.lastname: Audinot
authors.forename: Philippe
authors.initials: P
authors.lastname: Delagrange
authors.forename: Jean A
authors.initials: JA
authors.lastname: Boutin
mesh_terms: D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D006224:Cricetinae; D007192:Indenes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D008550:Melatonin / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D036103:Nanotechnology; D011808:Quinone Reductases / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D044094:Receptors, Melatonin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C513791:2,3-dimethoxy 7-hydroxy 10-methyl 5H 10H indeno(1,2-b)indol-10-one; D007192:Indenes; D007211:Indoles; D008024:Ligands; D044094:Receptors, Melatonin; C419642:NRH - quinone oxidoreductase2; D011808:Quinone Reductases; D008550:Melatonin