ArticleJournal of biomolecular screening2013
High-throughput FRET assay yields allosteric SERCA activators.
Article in Journal of biomolecular screening, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
61 citing papers in PubMed, 100 citations in OpenAlex.
- Positive allosteric modulator of SERCA pump NDC-1171 attenuates cardiac functional decline in mouse model of Duchenne muscular dystrophy.Function (Oxford, England) · 2026Article
- Insulin-regulated actin dynamics is disrupted in a human keratinocyte model of Hailey-Hailey disease.American journal of physiology. Cell physiology · 2026Article
- Guardians of T-Cell CaCells · 2026Review
- Neuronal Calcium Signaling and Cytoskeletal Dynamics in Neurodegeneration.International journal of molecular sciences · 2026Review
- Positive allosteric modulator of SERCA pump NDC-1171 attenuates cardiac functional decline in mouse model of Duchenne muscular dystrophy.bioRxiv : the preprint server for biology · 2026Article
- Development of activators for SERCA2a for heart failure treatments.European journal of medicinal chemistry · 2026Article
- The Landscape of SERCA2 in Cardiovascular Diseases: Expression Regulation, Therapeutic Applications, and Emerging Roles.Biomolecules · 2026Review
- HUWE1 in Skeletal Muscle Prevents Muscle Fatigue via Maintaining Iron and Calcium Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Insulin-Regulated Actin Dynamics is Disrupted in a Human Keratinocyte Model of Hailey Hailey Disease.bioRxiv : the preprint server for biology · 2025Article
- Pharmacological activation of SERCA2 reverses ER calcium dysregulation and depression-like behaviors in hyperglycemic mice.Scientific reports · 2025Article
- Gene and drug-mediated SERCA2a activation restores cardiac function and metabolic balance in diabetic mice.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Allosteric Modulation of SERCA Pumps in Health and Disease: Structural Dynamics, Posttranslational Modifications, and Therapeutic Potential.Journal of molecular biology · 2025Review
- Article
- SAR-Guided Development of Small-Molecule SERCA2a Activators: Discovery of Potent Indoline, Benzofuran, and Benzodioxole Analogs for Cardiovascular Applications.Journal of medicinal chemistry · 2025Article
- Machine Learning-Driven Discovery of Structurally Related Natural Products as Activators of the Cardiac Calcium Pump SERCA2a.ChemMedChem · 2025Article
- Endoplasmic reticulum stress-related deficits in calcium clearance promote neuronal dysfunction that is prevented by SERCA2 gene augmentation.Cell reports. Medicine · 2024Article
- SERCA Modulators Reveal Distinct Signaling and Functional Roles of T Lymphocyte CaInternational journal of molecular sciences · 2024Article
- A dual-targeted drug inhibits cardiac ryanodine receptor CaLife science alliance · 2024Article
- Mechanisms for cardiac calcium pump activation by its substrate and a synthetic allosteric modulator using fluorescence lifetime imaging.PNAS nexus · 2024Article
- 1,4-Benzothiazepines with Cyclopropanol Groups and Their Structural Analogues Exhibit Both RyR2-Stabilizing and SERCA2a-Stimulating Activities.Journal of medicinal chemistry · 2023Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Using fluorescence resonance energy transfer (FRET), we performed a high-throughput screen (HTS) in a reconstituted membrane system, seeking compounds that reverse inhibition of sarcoplasmic reticulum Ca-ATPase (SERCA) by its cardiac regulator, phospholamban (PLB). Such compounds have long been sought to correct aberrant Ca(2+) regulation in heart failure. Donor-SERCA was reconstituted in phospholipid membranes with or without acceptor-PLB, and FRET was measured in a steady-state fluorescence microplate reader. A 20 000-compound library was tested in duplicate. Compounds that decreased FRET by more than three standard deviations were considered hits. From 43 hits (0.2%), 31 (72%) were found to be false-positives upon more thorough FRET testing. The remaining 12 hits were tested in assays of Ca-ATPase activity, and six of these activated SERCA significantly, by as much as 60%, and several also enhanced cardiomyocyte contractility. These compounds directly activated SERCA from heart and other tissues. These results validate our FRET approach and set the stage for medicinal chemistry and preclinical testing. We were concerned about the high rate of false-positives, resulting from the low precision of steady-state fluorescence. Preliminary studies with a novel fluorescence lifetime plate reader show 20-fold higher precision. This instrument can dramatically increase the quality of future HTS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.