title: KB-R7943. Kanebo.
abstract: Kanebo is investigating KB-R7943, a Na+/Ca2+ ion exchange inhibitor, for the potential treatment of ischemia and reperfusion injury. It inhibited the outward Na+/Ca2+ exchange current (iNCX) more potently than the inward current under unidirectional flow conditions; however, inward and outward current were inhibited equally under bidirectional conditions. The drug was a competitive inhibitor to external calcium, and the inhibition was reversible with a recovery t1/2 of about 30 s. The mammalian Na+/Ca2+ exchanger forms a multigene family of homologous proteins comprising three isoforms, NCX1, NCX2 and NCX3. By examining chimeric constructs between NCX1 and NCX3 expressed in CCL39 cells, it has been demonstrated that it is the conserved internal repeat regions (alpha-1 and alpha-2) of the exchanger that are critical for the drug's action.
authors.affiliation: Ohio State University, Columbus 43210, USA. billman.1@pop.service.ohio-state.edu
authors.forename: G E
authors.initials: GE
authors.lastname: Billman
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000889:Anti-Arrhythmia Agents; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D013890:Thiourea