Dozens of commonly used drugs, including antibiotics, antinausea and anticancer medications, have a potential side effect of lengthening the electrical event that triggers contraction, creating an irregular heartbeat, or cardiac arrhythmia called acquired Long QT syndrome. While safe in their current dosages, some of these drugs may have a more therapeutic benefit at higher doses, but are limited by the risk of arrhythmia.

Through both computational and experimental validation, a multi-institutional team of researchers has identified a compound that prevents the lengthening of the heart's electrical event, or action potential, resulting in a major step toward safer use and expanded therapeutic efficacy of these medications when taken in combination. The team found that the compound, named C28, not only prevents or reverses the negative physiological effects on the action potential, but does not cause any change on the normal action potential when used alone at the same concentrations. The results, found through rational drug design, were published online Friday, May 14 in the Proceedings of the National Academy of Sciences.

The research team was led by Jianmin Cui, professor of biomedical engineering in the McKelvey School of Engineering at Washington University in St. Louis; Ira Cohen, MD, PhD, Distinguished Professor of Physiology and Biophysics, professor of medicine, and director of the Institute for Molecular Cardiology at the Renaissance School of Medicine at Stony Brook University; and Xiaoqin Zou, professor of physics, biochemistry, and a member of the Dalton Cardiovascular Research Center and Institute for Data Science and Informatics at the University of Missouri.