GS967 (GS-458967) is a highly selective late sodium channel current blocker.
In vitro: 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.
In vivo: GS967 causes a reduction of INaP in a frequency-dependent manner, consistent with use-dependent block (UDB). GS967 evokes more potent UDB of INaP (IC50=0.07 μM) than ranolazine (16 μM) and lidocaine (17 μM). GS967 is found to exert these same effects on a prototypical long QT syndromemutation (delKPQ). GS967 prevents ischemia-induced increases in alternans in the left atrium and left ventricle. GS967 reduces ischemia-induced increases in depolarization heterogeneity and repolarizationheterogeneity.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 40 mg/mL
Ethanol 40 mg/mL
Use-Dependent Block of Human Cardiac Sodium Channels by GS967.
Potet F, et al. Mol Pharmacol. 2016 Jul;90(1):52-60. PMID: 27136942.
Selective late sodium current blockade with GS-458967 markedly reduces ischemia-induced atrial and ventricular repolarization alternans and ECG heterogeneity.
Bonatti R, et al. Heart Rhythm. 2014 Oct;11(10):1827-35. PMID: 24953379.
A novel, potent, and selective inhibitor of cardiac late sodium current suppresses experimental arrhythmias.
Belardinelli L, et al. J Pharmacol Exp Ther. 2013 Jan;344(1):23-32. PMID: 23010360.
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