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Reduction of SR Ca2+ leak and arrhythmogenic cellular correlates by SMP-114, a novel CaMKII inhibitor with oral bioavailability

Neef, Stefan ; Mann, Christian ; Zwenger, Anne ; Dybkova, Nataliya ; Maier, Lars S.



Abstract

Sarcoplasmic reticulum (SR) Ca2+ leak induced by Ca2+/calmodulin-dependent protein kinase II (CaMKII) is centrally involved in atrial and ventricular arrhythmogenesis as well as heart failure remodeling. Consequently, treating SR Ca2+ leak has been proposed as a novel therapeutic paradigm, but compounds for use in humans are lacking. SMP-114 ("Rimacalib'') is a novel, orally available CaMKII ...

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