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| 5mg |
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| 25mg |
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Purity: ≥98%
GSK-5498A is a novel, potent and selective small molecule blocker of Calcium-Release Activated Calcium (CRAC) channel with IC50 of 1 uM; It inhibits mediator release from mast cells, and pro-inflammatory cytokine release from T-cells in a variety of species. Loss of function mutations in the two key proteins which constitute Calcium-Release Activated Calcium (CRAC) channels demonstrate the critical role of this ion channel in immune cell function. GSK-5498A was tested to demonstrate their ability to inhibit mediator release from mast cells, and pro-inflammatory cytokine release from T-cells in a variety of species. GSK-5498A completely inhibited calcium influx through CRAC channels. This led to inhibition of the release of mast cell mediators and T-cell cytokines from multiple human and rat preparations. Mast cells from guinea-pig and mouse preparations were not inhibited by GSK-5498A; however cytokine release was fully blocked from T-cells in a mouse preparation. GSK-5498A confirmed the critical role of CRAC channels in human mast cell and T-cell function, and that inhibition can be achieved in vitro. The rat displays a similar pharmacology to human, promoting this species for future in vivo research with this series of molecules. Together these observations provide a critical forward step in the identification of CRAC blockers suitable for clinical development in the treatment of inflammatory disorders.
| ln Vitro |
In human embryonic kidney cells, GSK-5498A (1 and 10 μM) blocks calcium influx through CRAC channels [1]. Using the calcium-sensitive dye Fluo4-AM, GSK-5498A (1 nM-10 μM) suppresses the thapsigargin-induced fluorescence signal in Jurkat cells (pIC50: 6.3) [1]. Cytostim-induced production of interferon-γ and IL-5 in PBMC is inhibited in a concentration-dependent manner by GSK-5498A (1 nM-10 μM) [1]. Rat tissue-resident mast cell degranulation is inhibited by GSK-5498A (1 μM–10 μM) [1]. In mice and rats, GSK-5498A (10 nM–10 μM) suppresses the release of T cell cytokines (IL-2) [1]. CRAC channels are more selectively bound by GSK-5498A (0-10 μM) than by other ion channels, enzymes, or G protein-coupled receptors [1].
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| References |
[1]. Rice LV, et al. Characterization of selective Calcium-Release Activated Calcium channel blockers in mast cells and T-cells from human, rat, mouse and guinea-pig preparations. Eur J Pharmacol. 2013 Mar 15;704(1-3):49-57.
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| Molecular Formula |
C18H11F6N3O
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|---|---|
| Molecular Weight |
399.2899
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| CAS # |
1253186-49-0
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| SMILES |
O=C(NC1=NN(CC2=C(F)C=CC=C2C(F)(F)F)C=C1)C3=C(F)C=CC=C3F
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| Synonyms |
GSK-5498A; GSK 5498A; GSK5498A
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~250.44 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (7.51 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 3 mg/mL (7.51 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5044 mL | 12.5222 mL | 25.0445 mL | |
| 5 mM | 0.5009 mL | 2.5044 mL | 5.0089 mL | |
| 10 mM | 0.2504 mL | 1.2522 mL | 2.5044 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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