Ruxolitinib as a CaMKII inhibitor for treatment of cardiac arrhythmias: Applications and prospects

Recent studies have highlighted the critical role of calcium/calmodulin-dependent protein kinase II (CaMKII) overactivation in the pathogenesis of various cardiac arrhythmias. Ruxolitinib, a Janus kinase inhibitor widely used for the treatment of myelofibrosis and acute graft-vs-host disease, has expanded its research horizons to include its potential as a CaMKII inhibitor in the treatment of cardiac arrhythmias. This article reviews the basic pharmacologic properties of ruxolitinib and delves into the role of CaMKII in cardiac arrhythmias, including its structural fundamentals, activation mechanisms, and association with arrhythmic conditions. Furthermore, the current state of CaMKII inhibitor research is discussed, with a special focus on the advances and clinical potential of ruxolitinib in this field. Studies indicate that ruxolitinib effectively inhibits CaMKII activity and has therapeutic potential against cardiac arrhythmias in animal models and at the cellular level. In addition, we address the critical issues that need to be resolved before the clinical application of ruxolitinib in arrhythmia treatment, including dosage concerns, long-term inhibitory effects, potential impacts on the nervous system, and efficacy across different types of arrhythmias. Future research directions involve further exploration of the clinical application potential of ruxolitinib, particularly in diseases such as heart failure, hypertrophic cardiomyopathy, dilated cardiomyopathy, and ischemic arrhythmias. In summary, the efficacy, low toxicity, and safety profile of ruxolitinib as a CaMKII inhibitor in the treatment of cardiac arrhythmias suggest a promising future for its development as a therapeutic drug in this domain.