Discovery of Novel Sphingosine-1-Phosphate-1 Receptor Agonists for the Treatment of Multiple Sclerosis

Park SJ, Yeon SK, Kim Y, Kim HJ, Kim S, Kim J, Choi JW, Kim B, Lee EH, Kim R, Seo SH, Lee J, Kim JW, Lee H-Y, Hwang H, Bahn Y-S, Cheong E, Park J-H, and Park KD.

Journal of Medicinal Chemistry, 2022

Scientists assess potential cardiotoxicity of potential multiple sclerosis drug candidates using Axion’s bioelectronic assay platform

Sphingosine-1-phosphate-1 (S1P1) receptor drugs are used for the treatment of relapsing-remitting forms of multiple sclerosis, but cardiovascular side effects associated with the immunomodulators have been reported. In this study, scientists developed and synthesized novel selective S1P1 receptor agonists and evaluated the activities, properties, and efficacy of the compounds using a multiplatform approach.

To assess the pro-arrhythmic potential of drug candidates, the researchers performed electrophysiological studies of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) on Axion’s noninvasive Maestro multielectrode array (MEA) platform. Based on the MEA results, as well as additional in vitro and in vivo testing, the authors identified a novel S1P1 receptor agonist for the treatment of multiple sclerosis.