CRAC Channel Inhibitor IV, GSK-7975A-CAS 1253186-56-9-Calbiochem

C₁₈H₁₂F₅N₃O₂

397.30

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.
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.

Cell permeable: yes
Primary Target
CRAC
Reversible: yes

Toxicity: Standard Handling (A)

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

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.

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

100

≥98% (HPLC)

solid

Calbiochem^®

OK to freeze
protect from light

off-white

DMSO: 50 mg/mL

−20℃

Packaged under inert gas

11 - Combustible Solids

WGK 3