产品说明书

Roflumilast N-oxide

Print
Chemical Structure| 292135-78-5 同义名 : 罗氟司特N-氧化物
CAS号 : 292135-78-5
货号 : A981483
分子式 : C17H14Cl2F2N2O4
纯度 : 99%+
分子量 : 419.21
MDL号 : MFCD04112984
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 250 mg/mL(596.36 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Roflumilast N-oxide is a PDE type 4 inhibitor. Co-administration of rifampicin and roflumilast led to a reduction in total PDE4 inhibitory activity of roflumilast by about 58%[2]. The PDE4 inhibitor roflumilast N-oxide acts (over) additively with simvastatin to prevent CSE-induced EMT (epithelial-mesenchymal transition) in WD-HBEC (well-differentiated human bronchial epithelial cells) in vitro[3]. Roflumilast-N-oxide fosters the expression of SPs (Surfactant proteins) in human AEC-II (alveolar epithelial cells type II) via increase of intracellular cAMP levels potentially contributing to improved alveolar host defence and enhanced resolution of inflammation[4]. Roflumilast N-oxide concentration-dependently triggered a rapid and persistent increase in ciliary beat frequency (CBF) and reversed the decrease in CBF following cigarette smoke extract (CSE). Roflumilast N-oxide protected differentiated human bronchial epithelial cells from reduced CBF and loss of ciliated cells following CSE[5]. Single treatment of db/db mice with 10 mg/kg Roflumilast N-oxide enhances plasma glucagon-like peptide-1 (GLP-1) 4-fold. Chronic treatment of db/db mice with Roflumilast N-oxide at 3 mg/kg shows prevention of disease progression. Furthermore, Roflumilast-N-oxide amplifies forskolin-induced insulin release in primary islets. Roflumilast-N-oxide also shows stronger glucose-lowering effects than its parent compound[6].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.39mL

0.48mL

0.24mL

11.93mL

2.39mL

1.19mL

23.85mL

4.77mL

2.39mL
参考文献

[2]Nassr N, Huennemeyer A, Herzog R, von Richter O, Hermann R, Koch M, Duffy K, Zech K, Lahu G. Effects of rifampicin on the pharmacokinetics of roflumilast and roflumilast N-oxide in healthy subjects. Br J Clin Pharmacol. 2009 Oct;68(4):580-7

[3]Milara J, Peiró T, Serrano A, Artigues E, Aparicio J, Tenor H, Sanz C, Cortijo J. Simvastatin Increases the Ability of Roflumilast N-oxide to Inhibit Cigarette Smoke-Induced Epithelial to Mesenchymal Transition in Well-differentiated Human Bronchial Epithelial Cells in vitro. COPD. 2015 Jun;12(3):320-31

[4]Höhne K, Schliessmann SJ, Kirschbaum A, Plönes T, Müller-Quernheim J, Tenor H, Zissel G. Roflumilast-N-oxide induces surfactant protein expression in human alveolar epithelial cells type II. PLoS One. 2012;7(7):e38369

[5]Milara J, Armengot M, Bañuls P, Tenor H, Beume R, Artigues E, Cortijo J. Roflumilast N-oxide, a PDE4 inhibitor, improves cilia motility and ciliated human bronchial epithelial cells compromised by cigarette smoke in vitro. Br J Pharmacol. 2012 Aug;166(8):2243-62

[6]Vollert S, Kaessner N, Heuser A, Hanauer G, Dieckmann A, Knaack D, Kley HP, Beume R, Weiss-Haljiti C. The glucose-lowering effects of the PDE4 inhibitors roflumilast and roflumilast-N-oxide in db/db mice. Diabetologia. 2012 Oct;55(10):2779-2788