GSK2190915 sodium salt

• CAT Number: I000713
• CAS Number: 1196070-26-4
• Molecular Formula: C38H42N3NaO4S
• Molecular Weight: 659.81
• Purity: ≥95%
• Synonyms: sodium 3-(3-(tert-butylthio)-1-(4-(6-ethoxypyridin-3-yl)benzyl)-5-((5-methylpyridin-2-yl)methoxy)-1H-indol-2-yl)-2,2-dimethylpropanoate
• Target: FLAP
• Solubility: DMSO: ≥ 32 mg/mL
• Storage: Store at -20°C
• IC50: 76 nM (inhibition of LTB4 in human blood 5 h incubation) [1]

GSK2190915(AM-803; Fiboflapon) sodium salt is a potent FLAP(5-Lipoxygenase-activating protein) inhibitor with binding IC50 of 2.9 nM.IC50 value: 76 nM (inhibition of LTB4 in human blood 5 h incubation) [1]Target: FLAP inhibitorGSK2190915 exhibits excellent preclinical toxicology and pharmacokinetics in rat and dog. GSK2190915 also demonstrated an extended pharmacodynamic effect in a rodent bronchoalveolar lavage (BAL) model [1]. Oral administration of AM803 (1 mg/kg) resulted in sustained inhibition of ex vivo ionophore-challenged whole blood LTB4 biosynthesis with >90% inhibition for up to 12 h and an EC50 of approximately 7 nM. When rat lungs were challenged in vivo with calcium-ionophore, AM803 inhibited LTB4 and cysteinyl leukotriene (CysLT) production with ED50s of 0.12 mg/kg and 0.37 mg/kg, respectively. The inhibition 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, AM803 dose-dependently reduced LTB4, CysLTs, plasma protein extravasation and neutrophil influx induced by peritoneal zymosan injection. Finally, AM803 increased survival time in mice exposed to a lethal intravenous injection of platelet activating factor (PAF) [2].

Reference

[1]. Stock NS, et al. 5-Lipoxygenase-activating protein (FLAP) inhibitors. Part 4: development of 3-[3-tert-butylsulfanyl-1-[4-(6-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. J Med 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 of acute inflammation. Eur J Pharmacol. 2010 Aug 25;640(1-3):211-8.