title: In vitro characterization of Ro 46-2005, a novel synthetic non-peptide endothelin antagonist of ETA and ETB receptors.
abstract: Ro 46-2005 is a new synthetic non-peptide endothelin (ET) receptor antagonist. In binding experiments, Ro 46-2005 proved to be equipotent (IC50 200-500 nM) for inhibition of [125]ET-1 binding on the two known ET receptor subtypes (ETA and ETB). Scatchard analysis was consistent with a competitive binding mode. Ro 46-2005 also inhibited the functional consequences of ET-1 stimulation: the ET-1 induced release of arachidonic acid from rat mesangial cells was inhibited with an IC50 of 1.8 microM.
authors.affiliation: Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Breu
authors.forename: B M
authors.initials: BM
authors.lastname: Löffler
authors.forename: M
authors.initials: M
authors.lastname: Clozel
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D001667:Binding, Competitive; D002460:Cell Line; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism*; D005260:Female; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D008861:Microsomes / Q000378:metabolism; D009036:Moths; D009130:Muscle, Smooth / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017466:Receptors, Endothelin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D013552:Swine; D014162:Transfection; D000096926:Benzenesulfonamides
chemical_list: D016718:Arachidonic Acid; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D011743:Pyrimidines; D017466:Receptors, Endothelin; D011994:Recombinant Proteins; D013449:Sulfonamides; C083751:Ro 46-2005; D000096926:Benzenesulfonamides