Synergistic FRET assays for drug discovery targeting RyR2 channels

A key therapeutic target for heart failure and arrhythmia is the deleterious leak through sarcoplasmic reticulum (SR) ryanodine receptor 2 (RyR2) calcium release channels. We have previously developed methods to detect the pathologically leaky state of RyR2 in adult cardiomyocytes by monitoring RyR2 binding to either calmodulin (CaM) or a biosensor peptide (DPc10). Here, we test whether these complementary binding measurements are effective as high-throughput screening (HTS) assays to discover small molecules that target leaky RyR2.

Source: Journal of Molecular and Cellular Cardiology - April 8, 2022 Category: Cytology Authors: RobynT. Rebbeck, Kenneth S. Ginsburg, Christopher Y. Ko, Anna Fasoli, Katherine Rusch, George F. Cai, Xiaoqiong Dong, David D. Thomas, Donald M. Bers, Razvan L. Cornea Source Type: research