GS967 is a potent, and selective inhibitor of cardiac late sodium current (late INa ).

Late INa:0.13 μM

GS967（10、100、300纳摩尔）完全抑制了ATX-II（10纳摩尔）增加心室肌细胞动作电位持续时间（APD）及APD变异性的效果，表观IC50值约为10纳摩尔，且减少了APD的搏动间变异性[1]。

GS967能防止和逆转晚期INa增强剂ATX-II及IKr抑制剂E-4031的致心律失常效应，并显著减轻methoxamine 1 clofilium引起的致心律失常效应，抑制缺血引起的心律失常[1]。GS967以频率依赖的方式减少INaP，符合使用依赖性阻断(UDB)。GS967引发的INaP UDB(半抑制浓度IC50=0.07μM)比ranolazine(16μM)和lidocaine(17μM)更强。GS967对典型的长QT综合征突变（delKPQ）[2]也表现出相同效应。GS967能阻止缺血引起的左心房和左心室alternans增加，减少缺血引起的去极化异质性和复极化异质性增加。GS967不改变心率、动脉血压、PR间期和QT间期或QRS持续时间，但在缺血期间轻度降低了心脏收缩性，这与晚期INa抑制一致[3]。

The IC50 of LY-364947 at different enzyme concentrations are determined by the filter-binding assay. Typically, 40 μL reactions in 50 mM HEPES at pH 7.5, 1 mM NaF, 200 μM pKSmad3(-3), and 50 mM ATP containing a titration of each inhibitor with concentrations of 1600, 800, 400, 200, 100, 50, 25, and 0 nM are incubated at 30°C for 30 min. The IC50 is calculated using a nonlinear regression method with GraphPad Prism software. The binding type is determined by plotting the correlation between enzyme concentrations and IC50 values.