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Arrhythmias

Ruxolitinib is a CaMKII inhibitor that can be repurposed to prevent arrhythmias

Nature Reviews Cardiology volume 20, page 580 (2023)Cite this article

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Ruxolitinib, an FDA-approved drug for the treatment of myelofibrosis, has now been identified via a drug repurposing screen as a Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor that prevents arrhythmias induced by CaMKII hyperactivity in mouse models without adverse effects on cognition. This discovery supports the use of drug repurposing screens to explore potential cardiac indications for clinically approved drugs.

“Our lab was the first (to our knowledge) to identify excessive myocardial CaMKII activity as a proarrhythmic signal and the first to show that CaMKII inhibition was antiarrhythmic,” comments Mark Anderson, senior investigator of the study. “Despite CaMKII being implicated in genetic arrhythmia syndromes, pharmaceutical and biotechnology companies have been reluctant to pursue development of CaMKII inhibitors for the understandable reason that CaMKII also has important roles in learning and memory,” he adds. To overcome this challenge, the investigators developed a genetically encoded CaMKII activity reporter that is suitable for high-throughput screening of thousands of FDA-approved drugs to identify those with CaMKII inhibitory properties.

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References

Original article

  • Reyes Gaido, O. E. et al. An improved reporter identifies ruxolitinib as a potent and cardioprotective CaMKII inhibitor. Sci. Transl. Med. 15, eabq7839 (2023)

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  1. Nature Reviews Cardiology http://www.nature.com/nrcardio/

    Karina Huynh

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  1. Karina Huynh
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Correspondence to Karina Huynh.

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Huynh, K. Ruxolitinib is a CaMKII inhibitor that can be repurposed to prevent arrhythmias. Nat Rev Cardiol 20, 580 (2023). https://doi.org/10.1038/s41569-023-00910-1

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