Roflumilast N-oxide
(Synonyms: 罗氟司特N-氧化物) 目录号 : GC37554
A PDE4 inhibitor and active metabolite of roflumilast
Cas No.:292135-78-5
Sample solution is provided at 25 µL, 10mM.
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Roflumilast N-oxide is an inhibitor of phosphodiesterase 4 (PDE4; IC50 = 2 nM) and an active metabolite of the PDE4 inhibitor roflumilast .1 It is selective for PDE4 over PDE1-3 and PDE5 (IC50s = >10,000 nM for all). It reduces TNF-α-induced ICAM-1 and eotaxin levels when used in combination with prostaglandin E2 in GM06114 human fetal lung fibroblasts (IC50s = 0.9 and 0.5 nM, respectively).2 It also reduces bFGF-induced and IL-1β augmented proliferation in the same cells. Roflumilast N-oxide (2 nM) reverses cigarette smoke extract-induced reductions in ciliary beat frequency in isolated human bronchial epithelial cells.3 Roflumilast N-oxide also increases plasma glucagon-like peptide 1 (GLP-1) levels in a glucose challenge in diabetic db/db mice when administered at a dose of 10 mg/kg, as well as prevents increases in blood glucose in db/db mice at 3 mg/kg per day.4
1.Hatzelmann, A., and Schudt, C.Anti-inflammatory and immunomodulatory potential of the novel PDE4 inhibitor roflumilast in vitroJ. Pharmacol. Exp. Ther.297(1)267-279(2001) 2.Sabatini, F., Petecchia, L., Boero, S., et al.A phosphodiesterase 4 inhibitor, roflumilast N-oxide, inhibits human lung fibroblast functions in vitroPulm. Pharmacol. Ther.23(4)283-291(2010) 3.Milara, J., Armengot, M., Ba?uls, P., et al.Roflumilast N-oxide, a PDE4 inhibitor, improves cilia motility and ciliated human bronchial epithelial cells compromised by cigarette smoke in vitroBr. J. Pharmacol.166(8)2243-2262(2012) 4.Vollert, S., Kaessner, N., Heuser, A., et al.The glucose-lowering effects of the PDE4 inhibitors roflumilast and roflumilast-N-oxide in db/db miceDiabetologia55(10)2779-2788(2012)
Cell experiment: | A549 cells are washed and cultured overnight in serum-free F-12 K medium supplemented with antibiotics, L-glutamine and HEPES. The starved cells are incubated with Neutrophil elastase (NE) for 30 min or vehicle (PBS), washed with PBS and then cultured in serum free F-12 K. After stimulation, cell supernatants are collected at 24 h (for cytokine measurements) and cell pellets are collected after 2 h (for mRNA expression analysis). Alternatively, A549 cells are pre-incubated for 2 h with Roflumilast N-oxide (RNO) (at 0.1 μM, 0.3 μM and 1 μM), vehicle (DMSO 0.01%) prior to the addition of NE. All experiments are performed in serum-free medium in triplicate and are repeated at least three times. At the end of the incubation period, culture supernatants are harvested and stored at -80°C until further analysis[1]. |
Animal experiment: | At 7 weeks of age, 16 h fasting mice receive a single oral dose of vehicle (4% methocel) or 10 mg/kg Roflumilast-N-oxide, and a glucose bolus of 2 g/kg body weight is co-administered as a physiological initiator for glucagon-like peptide-1 (GLP-1) secretion. Plasma GLP-1 is analyzed 60 min before, and 10 and 60 min after administration of Roflumilast-N-oxide and glucose. The effect of Roflumilast-N-oxide on plasma GLP-1 is also investigated in the absence of the glucose bolus[3]. |
References: [1]. Victoni T, et al. Roflumilast n-oxide associated with PGE2 prevents the neutrophil elastase-induced production of chemokines by epithelial cells. Int Immunopharmacol. 2016 Jan;30:1-8. | |
| Cas No. | 292135-78-5 | SDF | |
| 别名 | 罗氟司特N-氧化物 | ||
| Canonical SMILES | O=C(NC1=C(Cl)C=N(C=C1Cl)=O)C2=CC=C(OC(F)F)C(OCC3CC3)=C2 | ||
| 分子式 | C17H14Cl2F2N2O4 | 分子量 | 419.21 |
| 溶解度 | DMSO: 320 mg/mL (763.34 mM and warming) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3854 mL | 11.9272 mL | 23.8544 mL |
| 5 mM | 0.4771 mL | 2.3854 mL | 4.7709 mL |
| 10 mM | 0.2385 mL | 1.1927 mL | 2.3854 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet