A Large-Scale High-Throughput Screen for Modulators of SERCA Activity.

ABSTRACT: The sarco/endoplasmic reticulum Ca-ATPase (SERCA) is a P-type ion pump that transports Ca²⁺ from the cytosol into the endoplasmic/sarcoplasmic reticulum (ER/SR) in most mammalian cells. It is critically important in muscle, facilitating relaxation and enabling subsequent contraction. Increasing SERCA expression or specific activity can alleviate muscle dysfunction, most notably in the heart, and we seek to develop small-molecule drug candidates that activate SERCA. Therefore, we adapted an NADH-coupled assay, measuring Ca-dependent ATPase activity of SERCA, to high-throughput screening (HTS) format, and screened a 46,000-compound library of diverse chemical scaffolds. This HTS platform yielded numerous hits that reproducibly alter SERCA Ca-ATPase activity, with few false positiv

SUBMITTER: Bidwell PA 

PROVIDER: S-EPMC9776381 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature