AM103

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

AM103 是一种有效的选择性 FLAP 抑制剂 (IC50 = 4.2 nM)。

AM103 is an effective and selective inhibitor of FLAP (IC50 = 4.2 nM).(In Vitro):AM103 is against the 5 most common CYP isoforms with IC50s >30 μM for CYP2D6 and >50 μM for CYP3A4, CYP2C9, CYP2C19, and CYP1A2. AM103 shows IC50s of 350, 113, and 117 nM against human, rat, and mouse whole-blood ionophore-stimulated LTB4 production, respectively.(In Vivo):AM103 has high bioavailability of 64%, low clearance of 2.9 mL/min/kg, low volume of distribution of 0.41 L/kg, and a long i.v. half-life of 5.2 h in dogs. AM103 (10 mg/kg) inhibits the increase in CysLTs and EPO by approximately 60% and reduces the level of IL-5. In a model of chronic lung inflammation using ovalbumin-primed and challenged BALB/c mice, AM103 reduces eosinophil peroxidase, CysLTs, and IL-5 in the bronchoalveolar lavage fluid. AM103 increases survival time in mice exposed to a lethal intravenous injection of platelet-activating factor. In the rat lung challenged in vivo with calcium ionophore, AM103 inhibits LTB4 and cysteinyl leukotriene production with ED50 values of 0.8 and 1 mg/kg, respectively.

AM 103 has an IC50 value 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 IC50 values greater than 30 μM for CYP2D6 and >50 μM for CYPs 3A4, 2C9 2C19, and 1A2. AM103 is a novel, potent, and selective FLAP inhibitor with IC50 values of 350, 113, and 117 nM against human, rat, and mouse whole-blood ionophore-stimulated LTB4 production, respectively.

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. AM103 (1 mg/kg, p.o.) displays >50% inhibition for up to 6 h with a calculated EC50 of 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 ED50 values of 0.8 and 1 mg/kg, respectively, when rat lung is challenged in vivo with calcium ionophore. In this model, the EC50 derived 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.

AM 103

Immunology/Inflammation

FLAP

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1147872-22-7

633.78

C36H40N3NaO4S

>98% (HPLC)

In Vitro:?DMSO : 200 mg/mL (316.58 mM)

[NaH].COc1ccc(cn1)-c1ccc(Cn2c(CC(C)(C)C(O)=O)c(SC(C)(C)C)c3cc(OCc4ccccn4)ccc23)cc1

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(-20℃)

With Ice Pack

≥ 2 years