Fiboflapon-GSK2190915-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEFiboflaponCat. No.: HY-15874CAS No.: 936350-00-4Synonyms: GSK2190915; AM-803分式: CHNOS分量: 637.83作靶点: FLAP作通路: Immunology/Inflammation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 : 50 mg/mL

2、(78.39 mM; Need ultrasonic)H2O : 90% corn oilSolubility: 2.5 mg/mL (3.92 mM); Clear solution1/2 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 Fiboflapon (GSK2190915)FLAP 效选择性抑制剂，binding IC50值为 2.9 nM。IC50 & Target IC50: 76 nM (inhibition of LTB4 in human blood 5 h incubation) 1

3、.体外研究 Fiboflapon (AM-803) exhibits excellent preclinical toxicology and pharmacokinetics in rat and dog. Fiboflapon(AM-803) also demonstrated an extended pharmacodynamic effect in a rodent bronchoalveolar lavage (BAL)model 1.体内研究 Oral administration of Fiboflapon (AM-803: 1 mg/kg) results in sustain

4、ed inhibition of ex vivo ionophore-challenged whole blood LTB4 biosynthesis with 90% inhibition for up to 12 h and an EC50 of approximately7 nM. When rat lungs are challenged in vivo with calcium-ionophore, Fiboflapon (AM-803) inhibits LTB4 andcysteinyl leukotriene (CysLT) production with ED50s of 0

5、.12 mg/kg and 0.37 mg/kg, respectively. Theinhibition measured 16 h following a single oral dose of 3 mg/kg was 86% and 41% for LTB4 and CysLTs,respectively. In an acute inflammation setting, Fiboflapon dose-dependently reduced LTB4, CysLTs, plasmaprotein extravasation and neutrophil influx induced

6、by peritoneal zymosan injection. Finally, Fiboflaponincreases survival time in mice exposed to a lethal intravenous injection of platelet activating factor (PAF) 1.REFERENCES1. Stock NS, et al. 5-Lipoxygenase-activating protein (FLAP) inhibitors. Part 4: development of 3-3-tert-butylsulfanyl-1-4-(6-

7、ethoxypyridin-3-yl)benzyl-5-(5-methylpyridin-2-ylmethoxy)-1H-indol-2-yl-2,2-dimethylpropionic acid (AM803), a potent, oral, once daily FLAP inhibitor. JMed Chem. 2011 Dec 8;54(23):8013-29.2. Lorrain DS, et al. Pharmacology of AM803, a novel selective five-lipoxygenase-activating protein (FLAP) inhibitor in rodent models ofacute inflammation. Eur J Pharmacol. 2010 Aug 25;640(1-3):211-8.McePdfHeightCaution: Product has not been fully validated for medical applications.For resea