In vitro activity: GS967 (also known as GS-458967) is a novel, potent, and selective sodium channel inhibitor exhibiting potent antiarrhythmic effects in various in vitro and in vivo models. It inhibit cardiac late sodium current (late INa ) with IC50 values of 0.13 and 0.21 μM for ventricular myocytes and isolated hearts, respectively. The antiarrhythmic mechanism of GS967 has been attributed to preferential suppression of late sodium current. GS967 (10, 100, 300 nM) completely attenuates the effect of ATX-II (10 nM) to increase action potential duration (APD) and APD variability in ventricular myocytes, with an apparent IC50 value of ~10 nM and decreased the beat-to-beat variability of APD. GS967 selectively suppressed late I(Na) and prevented and/or reduced the incidence of experimentally induced arrhythmias in rabbit myocytes and hearts.

Kinase Assay:

Cell Assay: GS967 at10, 100, 300 nM completely attenuates the effect of ATX-II (10 nM) to increase action potential duration (APD) and APD variability in ventricular myocytes, with an apparent IC50 value of ~10 nM and decreased the beat-to-beat variability of APD