title: Development and application of Na+/Ca2+ exchange inhibitors.
abstract: The Na+/Ca2+ exchanger (NCX) is an ion transporter that exchanges Na+ and Ca2+ in either Ca2+ efflux or Ca2+ influx mode, depending on the ion gradients across the plasma membrane and the membrane potential. In heart, smooth muscle cells, neurons, and nephron cells, the NCX is thought to play an important role in the regulation of intracellular Ca2+ concentration. Recently, a novel selective inhibitor (KB-R7943 and SEA0400) of the Ca2+ influx mode of the NCX has been developed. NCX inhibitor is expected to be a pharmaceutical agent that offers effective protection against ischemia/reperfusion injury in several organs such as heart and kidney. Here, we summarize pharmacological profiles of KB-R7943 and SEA0400, the molecular mechanism of its action, and its future prospect as a novel pharmaceutical agent.
authors.affiliation: Department of Pharmacology, School of Medicine, Fukuoka University, Fukuoka, Japan. tiwamoto@cis.fukuoka-u.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Satomi
authors.initials: S
authors.lastname: Kita
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D006801:Humans; D010647:Phenyl Ethers / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D011485:Protein Binding; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000814:Aniline Compounds; D010647:Phenyl Ethers; C430918:SEA 0400; D019831:Sodium-Calcium Exchanger; D013890:Thiourea; D002118:Calcium