title: ORM-10103: a significant advance in sodium-calcium exchanger pharmacology?
abstract: The sodium-calcium exchanger (NCX) is an electrogenic transporter that is widely expressed in different tissues. In the heart, the NCX plays important roles in calcium ion homeostasis, excitation-contraction coupling and the electrophysiological properties of cardiac myocytes. Precise determination of the roles of the NCX has somewhat been hampered by a lack of selective small molecule inhibitors. In this issue of the BJP, Jost and colleagues present data on a new NCX inhibitor, ORM-10103, which has submicromolar EC50 values against cardiac forward and reverse exchange activity. The compound exhibits improved selectivity over existing small molecule NCX inhibitors and, in particular, appears to be without effect on L-type calcium channels at high concentrations. ORM-10103 could therefore have significant value for studies of the (patho)physiological roles of the NCX in the heart. Further pharmacological studies are required to investigate the actions of ORM-10103 on cardiac cells and tissues and to determine its effects on non-cardiac NCX isoforms.
authors.affiliation: National Heart and Lung Institute, Hammersmith Campus, Imperial College London, London, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: Terracciano
authors.forename: J C
authors.initials: JC
authors.lastname: Hancox
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*
chemical_list: C000590774:5-nitro-2-(2-phenylchroman-6-yloxy)pyridine; D000889:Anti-Arrhythmia Agents; D001578:Benzopyrans; D011725:Pyridines; D019831:Sodium-Calcium Exchanger
keywords: DAD; EAD; KB-R7943; NCX; Na+-Ca2+ exchange; ORM-10103; SEA0400; heart failure; sodium-calcium exchange