ArticleCell calcium2013
The action of selective CRAC channel blockers is affected by the Orai pore geometry.
Article in Cell calcium, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 132 citations in OpenAlex.
- Research progress on the role and mechanism of STIM and Orai protein-mediated store-operated calcium entry in cardiovascular diseases.Channels (Austin, Tex.) · 2026Review
- Iron and Other Metal Ions in Human Health and Disease.MedComm · 2026Review
- Developing Optogenetic Approaches to Study CaCold Spring Harbor perspectives in biology · 2026Review
- CRAC channels as targets for immunotherapy.Current opinion in immunology · 2026Review
- STIM/Orai-Mediated Store-Operated CaCells · 2026Review
- Targeted therapeutics for pancreatitis.Frontiers in physiology · 2026Review
- Differential Sensitivity of TRPC- and ORAI-Mediated Calcium Entries to 1‑[2-(4-Methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl]imidazole Chloride (SKF-96365).ACS pharmacology & translational science · 2025Article
- Store-operated calcium entry-based targets for novel cancer therapeutic development.The Journal of pharmacology and experimental therapeutics · 2025Review
- Calcium Oscillations Within Juxtaglomerular Cell Clusters Control Renin Release.Circulation research · 2025Article
- Inhibition of Renin Release, a Crucial Event in Homeostasis, is Mediated by Coordinated Calcium Oscillations within Juxtaglomerular Cell Clusters.bioRxiv : the preprint server for biology · 2025Article
- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- Synthetic Biology Meets CaCells · 2024Review
- Article
- Side-by-side comparison of published small molecule inhibitors against thapsigargin-induced store-operated Ca2+ entry in HEK293 cells.PloS one · 2024Article
- Neuronal Store-Operated Calcium Channels.Molecular neurobiology · 2023Review
- Orai, RyR, and IPCommunications biology · 2023Article
- Exercise Reduces Airway Smooth Muscle Contraction in Asthmatic Rats via Inhibition of IL-4 Secretion and Store-Operated CaAllergy, asthma & immunology research · 2023Article
- STIM1 and ORAI1 form a novel cold transduction mechanism in sensory and sympathetic neurons.The EMBO journal · 2023Article
- ORAI Calcium Channels: Regulation, Function, Pharmacology, and Therapeutic Targets.Pharmaceuticals (Basel, Switzerland) · 2023Review
- The SOCE Machinery: An Unbalanced Knowledge between Left and Right Ventricular Pathophysiology.Cells · 2022Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As the molecular composition of calcium-release activated calcium (CRAC) channels has been unknown for two decades, elucidation of selective inhibitors has been considerably hampered. By the identification of the two key components of CRAC channels, STIM1 and Orai1 have emerged as promising targets for CRAC blockers. The aim of this study was to thoroughly characterize the effects of two selective CRAC channel blockers on currents derived from STIM1/Orai heterologoulsy expressed in HEK293 cells. The novel compounds GSK-7975A and GSK-5503A were tested for effects on STIM1 mediated Orai1 or Orai3 currents by whole-cell patch-clamp recordings and for the effects on STIM1 oligomerisation or STIM1/Orai coupling by FRET microscopy. To investigate their site of action, inhibitory effects of these molecules were explored using Orai pore mutants. The GSK blockers inhibited Orai1 and Orai3 currents with an IC(50) of approximately 4μM and exhibited a substantially slower rate of onset than the typical pore blocker La(3+), together with almost no current recovery upon wash-out over 4min. For the less Ca(2+)-selective Orai1 E106D pore mutant, I(CRAC) inhibition was significantly reduced. FRET experiments indicated that neither STIM1-STIM1 oligomerization nor STIM1-Orai1 coupling was affected by these compounds. These CRAC channel blockers are acting downstream of STIM1 oligomerization and STIM1/Orai1 interaction, potentially via an allosteric effect on the selectivity filter of Orai. The elucidation of these CRAC current blockers represents a significant step toward the identification of CRAC channel-selective drug compounds.
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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.