"目录号: HY-14163
AM 103 是具有选择性的，有效的FLAP抑制剂，IC50值为 4.2 nM。
相关产品
MK-886-MK591-GSK2190915-AM679-MK-0591-
生物活性
Description
AM 103 is a potent and selectiveFLAPinhibitor, with anIC50value of 4.2 nM.
IC50& Target
IC50: 4.2 nM (FLAP)[1]
In Vitro
AM 103 has an IC50value of 349 nM in the human blood LTB4 inhibition assay. AM 103 has an excellent CYP profile against the 5 most common CYP isoforms with IC50values greater than 30 μM for CYP2D6 and >50 μM for CYPs 3A4, 2C9 2C19, and 1A2[1]. AM103 is a novel, potent, and selective FLAP inhibitor with IC50values of 350, 113, and 117 nM against human, rat, and mouse whole-blood ionophore-stimulated LTB4 production, respectively[2].
In Vivo
AM 103 has high bioavailability (64%), low clearance (2.9 mL/min/kg), low volume of distribution (0.41 L/kg), and a long i.v. half-life (5.2 h) in dogs. AM 103 (10 mg/kg q.i.d.) inhibits the increase in CysLTs and EPO by approximately 60%, and IL-5 levels are reduced to the concentrations obtained following saline treatment alone in mice[1]. AM103 (1 mg/kg, p.o.) displays >50% inhibition for up to 6 h with a calculated EC50of appr 60 nM, in a rat ex vivo whole-blood calcium ionophore-induced LTB4 assay. AM 103 inhibits LTB4 and cysteinyl leukotriene (CysLT) production with ED50values of 0.8 and 1 mg/kg, respectively, when rat lung is challenged in vivo with calcium ionophore. In this model, the EC50derived from plasma AM103 is appr 330 nM for inhibition of both LTB4 and CysLT. In a model of chronic lung inflammation using ovalbumin-primed and challenged BALB/c mice, AM103 reduces the concentrations of eosinophil peroxidase, CysLTs, and interleukin-5 in the bronchoalveolar lavage fluid. Finally, AM 103 increases survival time in mice exposed to a lethal intravenous injection of platelet-activating factor[2].
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