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Purity: ≥98%
GSK-7975A is a novel, potent and orally bioavailable inhibitor of CRAC (calcium release-activated calcium modulator). GSK-7975A prevents cytosolic calcium-associated injury of human pancreatic acinar cells and acute pancreatitis in 3 mouse models. GSK-7975A inhibited toxin-induced activation of ORAI1 and/or activation of Ca(2+) currents after Ca(2+) release, in a concentration-dependent manner, in mouse and human pancreatic acinar cells (inhibition >90% of the levels observed in control cells). ORAI1 inhibitors might be developed for the treatment of patients with pancreatitis.
| ln Vitro |
At 3 μM, GSK-7975A 50% lowers the release of histamine, leukotriene C4, and cytokines (TNFα, IL-5/-8/-13, and TNFα) while also reducing the FcεRI-consuming Ca2+ influx [1]. -7975A increases the full release of inflammatory cytokines from T cells and inhibits the release of media from mast cells in a variety of animal species. Calcium influx through CRAC channels is inhibited by GSK-7975A. This led to the inhibition of mast cells from different concentration preparations. GSK-7975A did not prevent the release of cytokines from mouse and guinea pig mast cells, but it totally stopped the release of cytokines from T cells in mouse preparations [2]. inhibits, in human pancreatic alveolar cells, toxin-induced ORAI1 activation subsequent to Ca2+ release and/or Ca2+ current activation as a concentration suspension (>90% inhibition level seen in control cells). In mice, GSK-7975A scissors stop necrosis from starting in human pancreatic alveolar cells [3].
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| ln Vivo |
In TLCS-AP, CER-AP, and FAEE-AP, GSK-7975A suppresses the systemic and local aspects of acute pancreatitis in a dose- and time-coupled manner. Only at low doses did GSK-7975A considerably reduce lung MPO; at elevated levels, it dramatically lowered pancreatic MPO levels, IL-6, and serum enzymes starch. The pancreatic histopathology of TLCS-AP, CER-AP, and FAEE-AP is considerably reduced by GSK-7975A [3].
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| References |
[1]. Ashmole I, et al. CRACM/Orai ion channel expression and function in human lung mast cells. J Allergy Clin Immunol. 2012 Jun;129(6):1628-35.e2.
[2]. 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. [3]. Wen L, et al. Inhibitors of ORAI1 Prevent Cytosolic Calcium-Associated Injury of Human Pancreatic Acinar Cells and Acute Pancreatitis in 3 Mouse Models. Gastroenterology. 2015 Aug;149(2):481-92.e7 |
| Molecular Formula |
C18H12F5N3O2
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|---|---|
| Molecular Weight |
397.298801422119
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| CAS # |
1253186-56-9
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| SMILES |
O=C(NC1=NN(CC2=CC=C(O)C=C2C(F)(F)F)C=C1)C3=C(F)C=CC=C3F
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| InChi Key |
CPYTVBALBFSXSH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H12F5N3O2/c19-13-2-1-3-14(20)16(13)17(28)24-15-6-7-26(25-15)9-10-4-5-11(27)8-12(10)18(21,22)23/h1-8,27H,9H2,(H,24,25,28)
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| Chemical Name |
2,6-difluoro-N-(1-(4-hydroxy-2-(trifluoromethyl)benzyl)-1H-pyrazol-3-yl)benzamide
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| Synonyms |
GSK-7975A; GSK 7975A; GSK7975A; GSK-7975; GSK 7975; GSK7975.
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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 : ≥ 90 mg/mL (~226.53 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.29 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 25.0 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: ≥ 2.5 mg/mL (6.29 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.29 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5170 mL | 12.5849 mL | 25.1699 mL | |
| 5 mM | 0.5034 mL | 2.5170 mL | 5.0340 mL | |
| 10 mM | 0.2517 mL | 1.2585 mL | 2.5170 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.
Products are for research use only; We do not sell to patients
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