Development of Ryanodine Receptor (RyR) Inhibitors for Skeletal Muscle and Heart Diseases

Abstract

Ryanodine receptors (RyR) are intracellular calcium (Ca²⁺) release channels on the sarcoplasmic reticulum of skeletal and cardiac muscles that play a central role in excitation-contraction coupling. Genetic mutations or posttranslational modifications of RyR causes hyperactivation of the channel, leading to various skeletal muscle and heart diseases. Currently, no specific treatments exist for most RyR-associated diseases. Recently, high-throughput screening (HTS) assays have been developed to identify potential candidates for treating RyR-related muscle diseases. These assays have successfully identified several compounds as novel RyR inhibitors, which are effective in animal models. In this review, we will focus on recent progress in HTS assays and discuss future perspectives of these promising approaches.