| 名稱 | Salmeterol Xinafoate |
| 描述 | Salmeterol Xinafoate (GR 33343X xinafoate) is a long-acting β2-adrenergic receptor agonist with anti-inflammatory effects, used in the treatment of asthma symptoms and chronic obstructive pulmonary disease (COPD) symptoms. |
| 激酶實驗 | The cells are rinsed twice with ice-cold phosphate-buffered saline and mechanically detached in ice-cold buffer containing 10 mM Tris·HCl, pH 7.4, 5 mM EDTA, 10 μg/mL benzamidine, 10 μg/mL soybean trypsin inhibitor (type II-S), and 5 μg/mL leupeptin (lysis buffer). The lysate is centrifuged at 45,000 ×g for 10 min at 4°C. The pellet is rehomogenized in lysis buffer, with a Potter-type homogenizer, and stored at ?80°C until use. The competition binding assays are performed in buffer containing 75 mM Tris·HCl, pH 7.4, 12.5 mM MgCl2, and 2 mM EDTA, using 1-5 μg of membrane protein, 50 pM 125I-CYP, and 0-100 μM unlabeled ligand in the presence of 100 μM GTP, for 60 min at 37°C. The binding reaction is terminated by dilution and rapid filtration through Whatman GF/C filters; the filters are washed three times with solution containing 25 mM Tris·HCl, pH 7.4, and 1 mM MgCl2. Nonspecific binding is determined in the presence of 5 μM (±)-propranolol. The radioactivity on the filters is counted with a γ-counte |
| 動物實驗 | Salmeterol is formulated in PBS.All mice are sensitized on days 0 and 14 by intraperitoneal injection of either PBS or 0.08 mg OVA and 0.1 mL aluminum hydroxide in 0.1 mL of PBS (pH 7.4). After sensitization, animals are exposed to aerosolized PBS-only (negative control), 1% OVS/PBS (acute exposure), 1% OVA/0.01% LPS/PBS (extra LPS exposure) or 1% OVA/0.01% LPS/salmeterol/PBS (sal treatment) for 40 min, once per day for 3 consecutive days (days 24-26). On day 27, the mice are killed and lungs are divided into two groups for analysis: the left lung lobes are lavaged three times with 1 mL of PBS with 1% fetal calf serum and 5 U/mL heparin, and the right halves are fixed by 4% paraformaldehyde for histological analysis. |
| 體外活性 | Salmeterol 顯著抑制RAW264.7和THP-1細胞產(chǎn)生的促炎介質(zhì)。Salmeterol 降低PgLPS介導(dǎo)的ERK1/2和JNK的磷酸化，但不影響p38 MAP激酶（MAP-K）。Salmeterol 通過抑制p65-NFκB的核內(nèi)轉(zhuǎn)移、NF-κB的轉(zhuǎn)錄活性及IκBα的磷酸化，減弱NF-κB的激活。Salmeterol 對WT β2AR（β1 Ki /β2 Ki比率約為1500）具有很高的選擇性，Ki值為1.5±0.4 nM。Salmeterol 阻止由腫瘤壞死因子-α引起的IRS-1Ser307的磷酸化水平。Salmeterol 單獨使用可以防止視網(wǎng)膜Müller細胞死亡（與25 mM葡萄糖相比，p<0.05）。與IRS-1 shRNA聯(lián)合使用時，相比于僅使用Salmeterol ，細胞死亡率顯著增加。此外，僅Salmeterol 處理顯著減少細胞色素C水平，當(dāng)與IRS-1 shRNA聯(lián)合使用時，此效果減弱。Salmeterol （100 μM）導(dǎo)致樹突細胞（DCs）凋亡，但在10 μM濃度下不影響DCs的分化和成熟。Salmeterol （10 μM）降低LPS激活的DCs中促炎細胞因子的mRNA和蛋白水平，抑制MAPK和NF-κB激活。 |
| 體內(nèi)活性 | OVA/LPS組合與salmeterol聯(lián)用可顯著且劑量依賴性地減少過敏小鼠增強的AHR。通過調(diào)節(jié)小鼠氣道炎癥，salmeterol有效對抗哮喘。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Ethanol : 12.1 mg/mL (20 mM)
DMSO : 60.4 mg/mL (100 mM)
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| 關(guān)鍵字 | corticosteroid | Salmeterol | Beta Receptor | therapy | inhibit | Adrenergic Receptor | Salmeterol Xinafoate | GR 33343X | combination | agonist | inflammatory | Inhibitor |
| 相關(guān)產(chǎn)品 | Tenofovir | Valproic Acid | Chloroquine phosphate | Emtricitabine | Dolutegravir intermediate-1 | Lamivudine | 5-Fluorouracil | Decanedioic acid | Dextran sulfate sodium salt (MW 4500-5500) | Stavudine | Kaempferol | Dimethyl fumarate |
| 相關(guān)庫 | 經(jīng)典已知活性庫 | 抗癌上市藥物庫 | EMA 上市藥物庫 | 抗病毒庫 | GPCR靶點分子庫 | 神經(jīng)退行性疾病化合物庫 | 膜蛋白靶向化合物庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |