Eleclazine (Synonyms: Dihydrobenzoxazepinone, GS-6615)

Eleclazine is an inhibitor of the cardiac late sodium current (I_Na).¹ It inhibits I_Na in HEK293 cells expressing the α subunit of the voltage-gated sodium channel (Na_v) isoform Na_v1.5 (IC₅₀ = 0.88 µM). Eleclazine is selective for the cardiac late I_Na over a panel of 11 cardiac ion channels at 1 µM, as well as Na_v1.1-1.4 and Na_v1.6-1.8 (IC₅₀s = ≥5 µM for all). Eleclazine reverses anemone toxin-II-induced activation of the monophasic action potential duration at 90% repolarization (MAPD₉₀) in isolated rabbit hearts (EC₅₀ = 0.72 µM). It inhibits S-T segment elevation in a rabbit model of cardiac ischemia-reperfusion injury induced by occlusion of the left anterior descending artery (EC₅₀ = 0.19 µM). Eleclazine decreases the incidence of ventricular tachycardia-ventricular fibrillation and mortality in a rabbit model of ischemia-induced arrhythmia induced by left circumflex artery ligation in a dose-dependent manner.

1.Zablocki, J.A., Elzein, E., Li, X., et al.Discovery of dihydrobenzoxazepinone (GS-6615) late sodium current inhibitor (late INai), a phase II agent with demonstrated preclinical anti-ischemic and antiarrhythmic propertiesJ. Med. Chem.59(19)9005-9017(2016)