Billman G E
Ohio State University, Columbus 43210, USA.
Curr Opin Investig Drugs. 2001 Dec;2(12):1740-5.
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.
佳丽宝正在研究KB-R7943（一种钠/钙离子交换抑制剂）用于潜在治疗缺血再灌注损伤的可能性。在单向流动条件下，它对向外的钠/钙交换电流（iNCX）的抑制作用比向内电流更强；然而，在双向条件下，向内和向外电流受到同等程度的抑制。该药物是细胞外钙的竞争性抑制剂，抑制作用是可逆的，恢复半衰期约为30秒。哺乳动物的钠/钙交换蛋白形成一个由同源蛋白组成的多基因家族，包括三种亚型，即NCX1、NCX2和NCX3。通过检测在CCL39细胞中表达的NCX1和NCX3之间的嵌合构建体，已证明交换蛋白保守的内部重复区域（α-1和α-2）对该药物的作用至关重要。
