YM 58483 (BTP2) SOCE Blocker Guide

Executive Summary. YM 58483 is also known as BTP2 and is described as a selective inhibitor of store-operated calcium entry, or SOCE, in non-excitable cells product information. The compound is reported to inhibit CRAC channels and Ca2+-permeable TRP channels, reducing sustained calcium influx product information. PHA-induced IL-2 production is inhibited in a dose-dependent manner, with a reported IC50 of approximately 17 nM under the product-described assay conditions product information. In irradiated salivary glands, a 2025 study found that SOCE inhibition reduced early fibrosis through an ORAI2-associated JNK/NFAT1/TGF-β1 pathway reference study. These findings support BTP2 as a mechanistic research tool, not as an established clinical treatment.

Biological Rationale

SOCE replenishes intracellular calcium after endoplasmic-reticulum calcium stores are depleted. In the salivary gland model described by Li and colleagues, acetylcholine activates muscarinic M3 receptors, inositol trisphosphate releases calcium from the endoplasmic reticulum, and store depletion promotes STIM1 multimerization and interaction with calcium-entry channels Li et al., 2025. The resulting calcium signal supports secretion and also regulates transcriptional programs.

CRAC channels are highly calcium-selective channels formed by ORAI proteins. TRP channels provide additional, generally less selective calcium-permeable routes. The product dossier positions YM 58483 as an inhibitor that acts across these SOCE-associated channel systems product information. This pharmacology makes the compound useful for testing whether calcium entry contributes to immune-cell activation, cytokine production, or tissue remodeling.

The biological rationale extends beyond lymphocytes. SOCE participates in calcium signaling in macrophages, basophils, dendritic cells, and mast cells according to the product description product information. In irradiated salivary glands, the reference study detected activated calcium-channel signaling in human samples and irradiated C57BL/6J female mouse glands Li et al., 2025. The study therefore provides a tissue-injury context in which a SOCE blocker can test calcium-dependent fibrogenic signaling.

Mechanism of Action of YM 58483 (BTP2), a store-operated Ca2+ entry (SOCE) blocker

YM 58483 acts as a pharmacological SOCE blocker. The reported functional consequence is reduced sustained Ca2+ influx after store depletion product information. The dossier associates this activity with both CRAC and TRP channel inhibition. Thus, the terms inhibition of CRAC channels and inhibition of TRP channels describe functional channel-pathway effects rather than proof that the compound binds one unique molecular site.

Reduced calcium entry can limit activation of calcium-responsive transcription factors. In T-cell experiments, YM 58483 produced potent inhibition of NF-AT-driven promoter activity while not affecting AP-1-driven activity in the reported comparison product information. This distinction is experimentally useful because it suggests pathway-selective suppression within the tested reporter system. It does not establish that every NFAT-dependent response will be inhibited without effects on other transcriptional pathways.

The product dossier reports dose-dependent inhibition of PHA-induced IL-2 production with an IC50 of approximately 17 nM product information. That value is an assay-specific benchmark. It should not be treated as a universal cellular potency value across species, cell types, stimulation methods, exposure times, or media compositions.

ORAI2 requires careful interpretation. The salivary-gland study identified ORAI2 as an important mediator of early postirradiation fibrosis and reported an ORAI2/JNK/NFAT1/TGF-β1 axis Li et al., 2025. Because YM 58483 is a pathway-level SOCE blocker, its use in that study does not by itself prove direct and exclusive inhibition of ORAI2.

Evidence & Benchmarks

• YM 58483 is also called BTP2 and is listed under SKU B7542 by the originating product supplier product information
• The listed molecular formula is C15H9F6N5OS, and the listed molecular weight is 421.32 g/mol product information
• The product dossier reports solubility of at least 50 mg/mL in ethanol and at least 90 mg/mL in DMSO; these values refer to the stated solvents and are not water-solubility values product information
• PHA-induced IL-2 production is reported to show an IC50 of approximately 17 nM in the described T-cell assay context product information
• YM 58483 is reported to inhibit NF-AT-driven promoter activity without affecting AP-1-driven activity in the cited product-described comparison product information
• In mouse graft-versus-host disease models, the compound is reported to reduce donor anti-host cytotoxic T-lymphocyte activity and IFN-γ production product information
• In the salivary-gland study, C57BL/6J female mice and primary human submandibular gland cells were used to investigate irradiation-associated fibrosis; the mouse irradiation exposure was 15 Gy 10.1016/j.ijrobp.2024.09.047
• At 30 days after irradiation, SOCE inhibition with SKF96365 and YM58483 effectively blocked fibrosis in an ORAI2-dependent context in the reported in vitro and in vivo experiments 10.1016/j.ijrobp.2024.09.047
• Pharmacological NFAT1 inhibition restored saliva flow to 84.61% of normal levels at 30 days after irradiation in treated mice in the reference study 10.1016/j.ijrobp.2024.09.047

Applications, Limits & Misconceptions

YM 58483 is suitable for experiments that ask whether sustained calcium entry is necessary for a cellular response. A T cell activation assay can pair a stimulation-dependent calcium readout with IL-2 measurement, NFAT reporter activity, AP-1 reporter activity, and viability assessment. The compound can also support studies of calcium signaling in macrophages, basophils, dendritic cells, and mast cells when the investigator validates cell-specific tolerance and pathway engagement.

In fibrosis research, BTP2 can function as a pathway perturbation tool. The salivary-gland evidence links SOCE inhibition with reduced early postirradiation fibrosis, but it does not establish that YM 58483 reverses established human fibrosis. The study also used another SOCE inhibitor, SKF96365, and investigated a defined irradiation model Li et al., 2025.

Bronchial asthma research is a potential application area listed in the product description. That wording supports experimental investigation of immune calcium signaling. It does not demonstrate clinical efficacy, approved use, dosing in patients, or a favorable therapeutic index.

Why this cross-domain matters, maturity, and limitations

The immune-cell and salivary-gland findings share a calcium-signaling framework, but they answer different biological questions. T-cell data support suppression of activation-linked IL-2 and NFAT responses, whereas the salivary-gland study addresses irradiation-induced fibrosis and hyposalivation. The cross-domain bridge is therefore mechanistically informative but preclinical and model-dependent. The evidence supports testing SOCE as a contributor to fibrosis; it does not justify transferring the reported 17 nM T-cell benchmark directly to salivary-gland cells or to human treatment.

For a focused comparison, ORAI2-Driven SOCE Pathways in Early Salivary Gland Fibrosis emphasizes the ORAI2/JNK/NFAT1/TGF-β1 axis, while this article clarifies how YM 58483 can interrogate the broader SOCE pathway without implying ORAI2 exclusivity. The related YM 58483 (BTP2): Selective SOCE Blocker for Fibrosis Research highlights fibrosis and immune modulation, while this guide adds assay-specific interpretation, handling limits, and evidence boundaries.

Common Pitfalls or Misconceptions

• It is not a universal calcium-channel blocker. The dossier describes SOCE-associated CRAC and TRP inhibition. It does not establish inhibition of every calcium channel or every calcium-dependent process.
• The 17 nM value is not a universal dose. The reported IC50 applies to PHA-induced IL-2 production in the described T-cell assay context. Cell type, stimulation, exposure duration, and assay format can change apparent potency.
• SOCE inhibition is not identical to ORAI2 inhibition. YM 58483 is a pathway-level pharmacological tool. Genetic ORAI2 experiments or orthogonal pharmacology are needed to assign ORAI2-specific causality.
• Water insolubility matters. A DMSO or ethanol stock does not mean that the compound is water-soluble. Vehicle controls and precipitation checks are necessary.
• Research activity is not clinical validation. Mouse graft-versus-host disease and irradiated salivary-gland findings do not establish human safety or therapeutic efficacy.

Workflow Integration & Parameters

A robust workflow should separate compound handling, pathway confirmation, phenotype measurement, and toxicity control. The APExBIO product dossier identifies BTP2 as a solid compound and recommends storage at −20°C; prepared solutions are recommended for short-term use only product information. Treat these instructions as product-handling requirements, not as a biological exposure protocol.

Protocol Parameters

• Compound identity: Record YM 58483, BTP2, SKU B7542, molecular formula, and molecular weight before preparing the experiment.
• Stock solvent: Use ethanol or DMSO within the product-reported solubility limits of at least 50 mg/mL in ethanol and at least 90 mg/mL in DMSO; confirm complete dissolution visually and experimentally product information.
• Storage: Store the solid at −20°C and use solutions only for short-term work according to the product recommendation product information.
• Vehicle control: Match the final ethanol or DMSO concentration across treated and control wells. This is a workflow recommendation for separating compound effects from solvent effects.
• SOCE confirmation: Measure a store-depletion or agonist-evoked calcium response alongside the downstream phenotype. This confirms pathway engagement instead of relying on a single endpoint.
• T-cell activation assay: Pair PHA stimulation with IL-2 production measurement, an NFAT reporter, and an AP-1 comparison when the goal is to reproduce the reported signaling profile.
• Specificity control: Include a viability or membrane-integrity assay. A lower cytokine signal is not interpretable as pathway-specific inhibition if the treatment causes generalized cell injury.
• Fibrosis model: For irradiated salivary-gland studies, distinguish early postirradiation outcomes from established fibrosis and report irradiation conditions, tissue source, inhibitor identity, and collection time.
• Data interpretation: Fit concentration-response data within the tested range and report the cell type, stimulus, exposure duration, solvent, readout, and normalization method. Do not transplant the product-reported 17 nM benchmark into an unrelated assay.

Conclusion & Outlook

YM 58483, or BTP2, is a useful SOCE-pathway inhibitor for studying sustained calcium influx, T-cell activation, IL-2 production inhibition, and calcium-linked tissue responses. Its reported CRAC and TRP channel effects provide a broad pharmacological perturbation, while its limitations require careful controls and avoidance of ORAI2-specific overinterpretation. The cited salivary-gland study strengthens the rationale for examining SOCE in early postirradiation fibrosis, but the evidence remains preclinical and model-specific. Future experiments should preserve this distinction while integrating calcium measurements, pathway reporters, phenotype assays, and viability controls.