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Updated: Jun 24, 2026

High-throughput Screening for Small-molecule Modulators of Inward Rectifier Potassium Channels

High-throughput Screening for Small-molecule Modulators of Inward Rectifier Potassium Channels

Published on: January 27, 2013

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

Philip A Bidwell¹, Samantha L Yuen², Ji Li²

¹Department of Medicine, Cardiovascular Division, University of Minnesota, Minneapolis, MN 55455, USA.

|December 23, 2022

Summary

Researchers screened 46,000 compounds to find small molecules that activate the sarco/endoplasmic reticulum Ca-ATPase (SERCA) pump, crucial for muscle function. Several compounds showed promise in enhancing SERCA activity and Ca2+ uptake.

Keywords:

calcium ATPase calcium transport cardiac muscle drug discovery heart failure membrane transport

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Purification of the Sarco-Endoplasmic Reticulum Ca2+-ATPase from Rabbit Muscle

Purification of the Sarco-Endoplasmic Reticulum Ca²⁺-ATPase from Rabbit Muscle

Published on: March 21, 2025

Area of Science:

Biochemistry
Molecular Biology
Pharmacology

Background:

The sarco/endoplasmic reticulum Ca-ATPase (SERCA) is vital for Ca2+ homeostasis and muscle function.
Dysfunctional SERCA contributes to muscle disorders, particularly in the heart.
Activating SERCA presents a therapeutic strategy for muscle dysfunction.

Purpose of the Study:

To identify small-molecule drug candidates that activate SERCA.
To develop and implement a high-throughput screening (HTS) assay for SERCA activators.

Main Methods:

Adapted an NADH-coupled assay for Ca-dependent SERCA ATPase activity into an HTS format.
Screened a library of 46,000 diverse chemical compounds.
Validated hits using secondary assays measuring both ATPase activity and Ca2+ transport in cardiac and skeletal SERCA isoforms.

Main Results:

Identified numerous compounds that reproducibly alter SERCA Ca-ATPase activity with low false positives.
Nearly all top hits enhanced Ca2+ uptake in both cardiac and skeletal SR, with some exhibiting isoform specificity.
Classified compounds based on their distinct effects on Ca2+ uptake and ATPase activity.

Conclusions:

The HTS platform successfully identified SERCA-activating compounds.
Dual analysis of ATPase activity and Ca2+ transport is crucial for compound selection.
Further research is needed to determine the therapeutic potential of identified compound classifications.