title: Discovery of novel adenylyl cyclase inhibitor by cell-based screening.
abstract: We screened 2400 compounds to find novel inhibitors of the adenylyl cyclase (AC)-protein kinase A (PKA)-cAMP response-element-binding protein (CREB) signaling pathway (AC/PKA/CREB pathway). Using a multistep cell-based screening system employing split luciferase technique, we narrowed down the candidates effectively from 2400 chemical compounds and identified a novel AC inhibitor (compound 1). Since dysregulation of the AC/PKA/CREB pathway is known to cause diseases not only in the nervous system but also in other organs, compound 1 is expected to be developed as a medicine for these diseases.
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Innovative Life Science, University of Toyama.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mano
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ishimoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Okada
authors.forename: Naoki
authors.initials: N
authors.lastname: Toyooka
authors.forename: Hisashi
authors.initials: H
authors.lastname: Mori
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D000262:Adenylyl Cyclases