Fiboflapon  (Synonyms: GSK2190915; AM-803)

Fiboflapon (GSK2190915; AM-803) is a potent and orally bioavailable 5-lipoxygenase-activating protein (FLAP) inhibitor with a potency of 2.9 nM in FLAP binding, an IC₅₀ of 76 nM for inhibition of LTB4 in human blood^[1].

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Oral administration of Fiboflapon (AM-803: 1 mg/kg) results 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 are challenged in vivo with calcium-ionophore, Fiboflapon (AM-803) inhibits 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, Fiboflapon dose-dependently reduced LTB4, CysLTs, plasma protein extravasation and neutrophil influx induced by peritoneal zymosan injection. Finally, Fiboflapon increases survival time in mice exposed to a lethal intravenous injection of platelet activating factor (PAF)^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

637.83

Solid

C₃₈H₄₃N₃O₄S

936350-00-4

CC(C(O)=O)(C)CC1=C(SC(C)(C)C)C2=CC(OCC3=CC=C(C)C=N3)=CC=C2N1CC4=CC=C(C5=CN=C(OCC)C=C5)C=C4

Room temperature in continental US; may vary elsewhere.

• [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  [Content Brief]

  [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.  [Content Brief]