5.34351

CRAC Channel Inhibitor IV, GSK-7975A

• 別名: 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
• 実験式（ヒル表記法）: C₁₈H₁₂F₅N₃O₂
• CAS番号: 1253186-56-9
• 分子量: 397.30
• MDL番号: MFCD28411366
• UNSPSCコード: 12352200
• NACRES: NA.77

特性

• アッセイ: ≥98% (HPLC)
• 品質水準: 100
• フォーム: solid
• メーカー／製品名: Calbiochem^®
• 保管条件: OK to freeze; protect from light
• 色: off-white
• 溶解性: DMSO: 50 mg/mL
• 保管温度: −20°C
• SMILES記法: FC(F)(F)c1c(ccc(c1)O)C[n]2nc(cc2)NC(=O)c3c(cccc3F)F
• 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)
• InChI Key: CPYTVBALBFSXSH-UHFFFAOYSA-N

詳細

詳細

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.

生物化学的／生理学的作用

Cell permeable: yes

Primary Target
CRAC

Reversible: yes

包装

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

再構成

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

その他情報

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.

法的情報

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

安全性情報

• 保管分類コード: 11 - Combustible Solids
• WGK: WGK 3
• 引火点(°F): Not applicable
• 引火点(℃): Not applicable