5.34351

CRAC Channel Inhibitor IV, GSK-7975A

• Synonym(s): CRAC Channel Inhibitor IV, GSK-7975A, 2,6-Difluoro-N-(1-(4-hydroxy-2-(trifluoromethyl)benzyl)-1H-pyrazol-3-yl)benzamide, CRAC Chanel Blocker, GSK-7975A, GSK7975A
• Empirical Formula (Hill Notation): C₁₈H₁₂F₅N₃O₂
• CAS Number: 1253186-56-9
• Molecular Weight: 397.30
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• Assay: ≥98% (HPLC)
• Quality Level: 100
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: off-white
• solubility: DMSO: 50 mg/mL
• storage temp.: −20°C

Description

General description

A cell permeable pyrazol derivative that acts as a specific CRAC (Ca²⁺ release-activated Ca²⁺ entry) channel blocker (IC₅₀ = 800 nM in RBL cells) possibly downstream of STIM1 oligomerization and STIM1/Orail interaction. Shown to fully block Orail1 and at 10 µM in HeK293 cells (t_1/2 = 75-100 s), but with 2.5-fold slower than La3+ kinetically. Also inhibits Orail3 currents with similar potency but with faster kinetics (t_1/2 = ~20s). Exhibits good selectivity against a panel of more than 16 ion channels, only with reduced effects on L-type Ca²⁺ (CaV1.2) and TRPV6 channels. Inhibits store-operated Ca2+ entry (IC₅₀ = 3.4 µM) at 10 µM in normal pancreatic acinar cells, but not in pancreatic acinar cell line AR42J which has a neuronal phenotype and hepatocytes, and does not affect acetylcholine or cholecystokinin induced Ca²⁺ spiking. Shown to block palmitoleic acid ethyl ester-induced trysin and protease activitiest and abolish necrosis. Additionally, reduces Fc?RI-dependent Ca²⁺ influx, at 3 µM and reduces the release of histamine, leukotriene C4, and cytokines (IL-5/-8/-13 and TNFα) by up to 50% in human lung mast cells (HLMC) and from rat, mouse and guinea-pig preparations.

A cell permeable pyrazol derivative that acts as a specific CRAC (Ca²⁺ release-activated Ca²⁺ entry) channel blocker (IC₅₀ = 800 nM in RBL cells) possibly downstream of STIM1 oligomerization and STIM1/Orail interaction. Shown to fully block Orail1 and at 10 µM in HeK293 cells (t_1/2 = 75-100 s), but with 2.5-fold slower than La3+ kinetically. Also inhibits Orail3 currents with similar potency but with faster kinetics (t_1/2 = ~20s). Exhibits good selectivity against a panel of more than 16 ion channels, only with reduced effects on L-type Ca²⁺ (CaV1.2) and TRPV6 channels. Inhibits store-operated Ca2+ entry (IC₅₀ = 3.4 µM) at 10 µM in normal pancreatic acinar cells, but not in pancreatic acinar cell line AR42J which has a neuronal phenotype and hepatocytes, and does not affect acetylcholine or cholecystokinin induced Ca²⁺ spiking. Shown to block palmitoleic acid ethyl ester-induced trysin and protease activitiest and abolish necrosis. Additionally, reduces Fc?RI-dependent Ca²⁺ influx, at 3 µM and reduces the release of histamine, leukotriene C4, and cytokines (IL-5/-8/-13 and TNFα) by up to 50% in human lung mast cells (HLMC) and from rat, mouse and guinea-pig preparations.

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
CRAC

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Other Notes

Voronina, S., et al. 2015. Biochem. J.465, 405.
Derler, I., et al. 2013. Cell Calcium.53, 139l.
Gerasimenko, J.V., et al. 2013. PNAS.110, 13186.
Louise, V., et al. 2013. Eur. J. Pharmacol.704, 49.

Ashmole, I., et al. 2012. J. Aller. Clin. Immun.129, 1628.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable