CRAC Channel Inhibitor IV, GSK-7975A

Описание:

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 (t1/2 = 75-100 s), but with 2.5-fold slower than La3+ kinetically. Also inhibits Orail3 currents with similar potency but with faster kinetics (t1/2 = ~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.