下载本文档
版权说明:本文档由用户提供并上传,收益归属内容提供方,若内容存在侵权,请进行举报或认领
文档简介
1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERoflumilast N-oxideCat. No.: HY-100639CAS No.: 292135-78-5分式: CHClFNO分量: 419.21作靶点: Phosphodiesterase (PDE)作通路: Metabolic Enzyme/Protease储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 320
2、mg/mL (763.34 mM; Need ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.3854 mL 11.9272 mL 23.8544 mL5 mM 0.4771 mL 2.3854 mL 4.7709 mL10 mM 0.2385 mL 1.1927 mL 2.3854 mL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,并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Roflumilast N-oxide个 PDE 4 型抑制剂。IC50
3、 & Target PDE type 4 1体外研究Roflumilast N-oxide at 2 nM partly mitigates the cigarette smoke extract (CSE)-induced epithelial tomesenchymal transition (EMT) in WD-HBEC in vitro. Roflumilast N-oxide (2 nM) reverses the compromisedexpression of E-cadherin transcripts following CSE by 45%. The expression
4、 of collagen type I is abrogated1/2 Master of Small Molecules 您边的抑制剂师www.MedChemEby Roflumilast N-oxide (2 nM). The epithelial cell phenotype appears protected when cells are co-incubatedwith Roflumilast N-oxide (2 nM). Pre-incubation with Roflumilast N-oxide (2 nM) also partly attenuates thenuclear
5、 translocation of -catenin 2.体内研究 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 ofdisease progression. Roflumilast-N-oxide abolishes the incr
6、ease in blood glucose, reduces the increment inHbA1c by 50% and doubles fasted serum insulin compare with vehicle, concomitants with preservation ofpancreatic islet morphology. Furthermore, Roflumilast-N-oxide amplifies forskolin-induced insulin release inprimary islets. Roflumilast-N-oxide also sho
7、ws stronger glucose-lowering effects than its parent compound3.PROTOCOLCell Assay 1 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),
8、 washed with PBS and then cultured in serum free F-12 K. After stimulation, cell supernatants arecollected at 24 h (for cytokine measurements) and cell pellets are collected after 2 h (for mRNA expressionanalysis). Alternatively, A549 cells are pre-incubated for 2 h with Roflumilast N-oxide (RNO) (a
9、t 0.1 M, 0.3 M and 1 M), vehicle (DMSO 0.01%) prior to the addition of NE. All experiments are performed in serum-freemedium in triplicate and are repeated at least three times. At the end of the incubation period, culturesupernatants are harvested and stored at -80C until further analysis 1.MCE has
10、 not independently confirmed the accuracy of these methods. They are for reference only.Animal At 7 weeks of age, 16 h fasting mice receive a single oral dose of vehicle (4% methocel) or 10 mg/kgAdministration 3 Roflumilast-N-oxide, and a glucose bolus of 2 g/kg body weight is co-administered as a p
11、hysiological initiatorfor glucagon-like peptide-1 (GLP-1) secretion. Plasma GLP-1 is analyzed 60 min before, and 10 and 60 minafter administration of Roflumilast-N-oxide and glucose. The effect of Roflumilast-N-oxide on plasma GLP-1is also investigated in the absence of the glucose bolus 3.MCE has n
12、ot independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Victoni T, et al. Roflumilast n-oxide associated with PGE2 prevents the neutrophil elastase-induced production of chemokines byepithelial cells. Int Immunopharmacol. 2016 Jan;30:1-8.2. Milara J,et al.
13、Simvastatin Increases the Ability of Roflumilast N-oxide to Inhibit Cigarette Smoke-Induced Epithelial to MesenchymalTransition in Well-differentiated Human Bronchial Epithelial Cells in vitro. COPD. 2015 Jun;12(3):320-31.3. Vollert S, et al. The glucose-lowering effects of the PDE4 inhibitors roflumilast and roflumilast-N-oxide in db/db mice. Diabetologia. 2012Oct;55(10):2779-2788.Mce
温馨提示
- 1. 本站所有资源如无特殊说明,都需要本地电脑安装OFFICE2007和PDF阅读器。图纸软件为CAD,CAXA,PROE,UG,SolidWorks等.压缩文件请下载最新的WinRAR软件解压。
- 2. 本站的文档不包含任何第三方提供的附件图纸等,如果需要附件,请联系上传者。文件的所有权益归上传用户所有。
- 3. 本站RAR压缩包中若带图纸,网页内容里面会有图纸预览,若没有图纸预览就没有图纸。
- 4. 未经权益所有人同意不得将文件中的内容挪作商业或盈利用途。
- 5. 人人文库网仅提供信息存储空间,仅对用户上传内容的表现方式做保护处理,对用户上传分享的文档内容本身不做任何修改或编辑,并不能对任何下载内容负责。
- 6. 下载文件中如有侵权或不适当内容,请与我们联系,我们立即纠正。
- 7. 本站不保证下载资源的准确性、安全性和完整性, 同时也不承担用户因使用这些下载资源对自己和他人造成任何形式的伤害或损失。
最新文档
- 纯化水设备技术参数
- 信息网会员协议
- 重症医学科感控相关知识考试试题
- 高中人工智能探究式教学模式研究
- (a)概率统计试题及部分答案
- 2024年T电梯修理复审模拟题及答案
- FZ∕T 98007-2011 电子单纱强力仪
- 病人监护仪相关行业投资方案范本
- 2023年驾照考试安全行车常识知识竞赛题库及答案(共180题)
- 厨房里的物质与变化科学 教科版 六年级 下册
- 长沙市初中毕业学业考试(生地会考)试卷地理真题含答案
- 捐赠设备协议书范本(5篇)
- 师德教育感悟-心中有爱眼中有光
- 2023年娄底市中医院医护人员招聘笔试题库及答案解析
- 17J927-1-车库建筑构造-高清版
- 泌尿系统疾病的药物治疗课件
- 绩效管理系统典型问题及解决方案
- 鼻-前颅底肿瘤课件
- 地下建筑结构-浅埋式矩形地下结构课程设计-计算书
- 餐饮管理 课程标准
- 课堂教学质量评估表(模板)
评论
0/150
提交评论