GSK-7975A - Calcium Channel 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGSK-7975ACat. No.: HY-12507CAS No.: 1253186-56-9分式: CHFNO分量: 397.3作靶点: Calcium Channel作通路: Membrane Transporter/Ion Channel; Neuronal Signaling储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO

2、: 90 mg/mL (226.53 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.5170 mL 12.5849 mL 25.1699 mL5 mM 0.5034 mL 2.5170 mL 5.0340 mL10 mM 0.2517 mL 1.2585 mL 2.5170 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次

3、添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 10 mg/mL (25.17 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 10 mg/mL (25.17 mM); Clear solution3. 请依序添加每种溶剂： 10%

4、 DMSO 90% corn oil1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 10 mg/mL (25.17 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 GSK-7975A效有服活性的 CRAC 通道抑制剂。体外研究 GSK-7975A reduces FcRI-dependent Ca2+ influx and 3 M GSK-7975A reduces the release of histamine,leukotriene C4, and cytokines (IL-5

5、/-8/-13 and TNF) by up to 50% 1. GSK-7975A inhibits mediator releasefrom mast cells, and pro-inflammatory cytokine release from T-cells in a variety species. GSK-7975Acompletely inhibits calcium influx through CRAC channels. This leads to inhibition of the release of mast cellmediators and T-cell cy

6、tokines from multiple human and rat preparations. Mast cells from guinea-pig andmouse preparations are not inhibited by GSK-7975A; however cytokine release is fully blocked from T-cellsin a mouse preparation 2. GSK-7975A inhibits toxin-induced activation of ORAI1 and/or activation of Ca2+currents af

7、ter Ca2+ release, in a concentration-dependent manner, in mouse and human pancreatic acinarcells (inhibition 90% of the levels observed in control cells). GSK-7975A also prevents activation of thenecrotic cell death pathway in mouse and human pancreatic acinar cells 3.体内研究 GSK-7975A inhibits local a

8、nd systemic features of acute pancreatitis in TLCS-AP, CER-AP, FAEE-AP, indose- and time-dependent manners. GSK-7975A significantly reduces increases in serum amylase, IL6, andpancreatic MPO levels; lung MPO is reduced significantly by low dose only. GSK-7975A markedly reducespancreatic histopatholo

9、gy in TLCS-AP, CER-AP, and FAEE-AP 3.PROTOCOLAnimal Mice: Acute pancreatitis is induced in C57BL/6J mice by ductal injection of taurolithocholic acid 3-sulfate orAdministration 3 intravenous administration of cerulein or ethanol and palmitoleic acid. Some mice then are given GSK-7975A, which inhibit

10、 ORAI1, at different time points to assess local and systemic effects. Sampling of GSK-7975A is at 1, 2, 4, 10, and 22 hours after osmotic minipump insertion from 3 mice/time point. Immediatelyafter humane killing, blood is collected into a heparinized tube, diluted 1:1 with sterile water, and thepa

11、ncreas is removed and homogenized. Standards and study samples (50 L from blood and 100 L frompancreas) are extracted by protein precipitation and centrifuged. Supernatants are dried under heatednitrogen (40C). Levels of GSK-7975A and GSK-6288B are determined 3.MCE has not independently confirmed th

12、e accuracy of these methods. They are for reference only.户使本产品发表的科研献 Biosci Rep. 2019 Jun 20. Science in Dentistry, University of Pennsylvania. 2019 Jun.See more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE1. Ashmole I, et al. CRACM/Orai

13、 ion channel expression and function in human lung mast cells. J Allergy Clin Immunol. 2012Jun;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 Pancreatitisin 3 Mouse Models. Gastroenterology. 2015 Aug;149(2):481-9