| 名稱 | Roflumilast |
| 描述 | Roflumilast (APTA 2217) is an orally available, long-acting inhibitor of phosphodiesterase (PDE) type 4 (PDE4), with anti-inflammatory and potential antineoplastic activities. Upon administration, roflumilast and its active metabolite roflumilast N-oxide selectively and competitively bind to and inhibit PDE4, which leads to an increase of both intracellular levels of cyclic-3', 5'-adenosine monophosphate (cAMP) and cAMP-mediated signaling. |
| 激酶實(shí)驗(yàn) | PDE activity is determined with some modifications. The assay mixture contain 50 mM Tris (pH 7.4), 5 mM MgCl2, 0.5 μM cAMP or cGMP, and [3H]cAMP or [3H]cGMP (about 30,000 cpm/assay), the indicated concentration of the inhibitor and an aliquot of the enzyme solution at a final assay volume of 200 μL. Stock solutions of the compounds are diluted 1:100 (v/v) in the Tris buffer mentioned above; appropriate dilutions are prepared in 1% (v/v) DMSO/Tris buffer, which are diluted 1:2 (v/v) in the assays to obtain the desired final concentrations of the inhibitors at a DMSO concentration of 0.5% (v/v). DMSO itself affected none of the PDE activities. After preincubation for 5 min at 37°C, the reaction is started by the addition of substrate (cAMP or cGMP) and the assays are incubated for further 15 min at 37°C. Then 50 μL of 0.2 N HCl is added to stop the reaction and the assays are left on ice for about 10 min. Following incubation with 25 μg of 5′-nucleotidase (Crotalus atrox snake venom) for 10 min at 37°C, the assays are loaded on QAE Sephadex A-25 (1 mL of bed volume in Poly-Prep chromatography columns). The columns are eluted with 2 mL of 30 mM ammonium formate (pH 6.0) and the eluate is counted for radioactivity. Results are corrected for blank values (measured in the presence of denatured protein) that are below 5% of total radioactivity. The amount of cyclic nucleotides hydrolyzed did not exceed 30% of the original substrate concentration[3]. |
| 體外活性 | 在體內(nèi)實(shí)驗(yàn)中,Roflumilast使氧化壓力下降.在動(dòng)物模型中,Roflumilast可一定程度抵抗肺炎（COPD相關(guān)）.在暴露于煙草7個(gè)月的小鼠肺中, Roflumilast（5 mg/kg/day ）誘導(dǎo)巨噬細(xì)胞,中性粒細(xì)胞,B細(xì)胞,樹突狀細(xì)胞,CD8+ T細(xì)胞,CD4+ T 細(xì)胞分別減少82%,78%,100%, 48%,88%和98%.博來霉素氣管內(nèi)給藥14天后,Roflumilast（5 mg/kg/day ）可適度降低小鼠BAL體液中過氧化氫脂質(zhì)的增高.在博來霉素處理以后,Roflumilast劑量依賴性降低肺部總羥脯氨酸含量,5 mg/kg/day可抑制47%,并降低肺部纖維化損傷和αI(I)膠原蛋白轉(zhuǎn)錄. |
| 體內(nèi)活性 | 在體外實(shí)驗(yàn)中,Roflumilast起免疫調(diào)節(jié)和抗炎活性作用。Rolfumilast對(duì)抗CD28和CD3抗體激活的CD4+ T細(xì)胞具有抑制作用（IC30：7 nM）,且分別對(duì)IL-2（IC20：1 nM）,IL-4（IC30：7 nM）,IL-5（IC25：13 nM）,以及 IFN-v（IC35：8 nM）的合成有抑制作用。在人類嗜中性粒細(xì)胞中,Roflumilast抑制LTB4合成（IC50：2 nM）。在酸性粒細(xì)胞和中性粒細(xì)胞中,Roflumilast對(duì)fMLP刺激的ROS形成有抑制作用,IC35 分別是7 nM和4 nM。在單核細(xì)胞中,Roflumilast對(duì)脂多糖誘導(dǎo)的TNF-α合成有抑制作用（IC40：21 nM）。在源于單核細(xì)胞的樹突狀細(xì)胞中,Roflumilast對(duì)脂多糖誘導(dǎo)的TNF-α合成有抑制效果（IC20： 5 nM）。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : 12 mg/mL (29.8 mM)
DMSO : 50 mg/mL (124 mM)
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| 關(guān)鍵字 | BY217 | Respiratory syncytial virus | BYK20869 | RSV | Phosphodiesterase (PDE) | BY-217 | inhibit | APTA2217 | Inhibitor | APTA-2217 | BYK-20869 | Roflumilast |
| 相關(guān)產(chǎn)品 | Icariin | Vardenafil hydrochloride | Apremilast | Indomethacin | Theophylline | Theobromine | Theophylline monohydrate | Isoprenaline hydrochloride | Ribavirin | Doxofylline |
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