AM 103

"目录号: HY-14163

Immunology/Inflammation-

AM 103 是具有选择性的，有效的FLAP抑制剂，IC50值为 4.2 nM。

FLAP

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].

References

[1].Hutchinson JH, et al. 5-lipoxygenase-activating protein inhibitors: development of 3-[3-tert-butylsulfanyl-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid (AM103). J Med Chem. 2009 Oct 8;52(19):5803-15.

[2].Lorrain DS, et al. Pharmacological characterization of 3-[3-tert-butylsulfanyl-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid (AM103), a novel selective 5-lipoxygenase-activating protein inhibitor that reduces acute and chronic inflammation. J Pharmacol Exp Ther. 2009 Dec;331(3):1042-50.