| 名稱 | Aclidinium bromide |
| 描述 | Aclidinium bromide (LAS-W 330) is a synthetic anticholinergic agent that is used as an inhalant for treatment of acute bronchospasm due to chronic bronchitis or emphysema. Aclidinium has not been implicated in causing liver enzyme elevations or clinically apparent acute liver injury. |
| 細(xì)胞實(shí)驗(yàn) | Human bronchial fibroblast proliferation is measured as previously outlined by colorimetric immunoassay based on BrdU incorporation during DNA synthesis using a cell proliferation enzyme-linked immunosorbent assay BrdU kit according to the manufacturer's protocol. Cells are seeded at a density of 3x103 cells/well on 96-well plates and incubated for 24 hours. Cells are then exposed to different experimental conditions. The 490 nm absorbance is quantified using a microplate spectrophotometer. Proliferation data refers to the absorbance values of BrdU-labeled cellular DNA content per well. Stimulation is expressed as x-fold proliferation over basal growth of the untreated control set as unity.(Only for Reference) |
| 激酶實(shí)驗(yàn) | Affinity assay: The affinity of Aclidinium for the different human muscarinic receptor subtypes at equilibrium is determined by measuring their ability to displace the binding of [3H]NMS to cell membrane preparations expressing one of the human muscarinic receptor subtypes. Protein concentrations are 8.1 μg/well, 10.0 μg/well, 4.9 μg/well, 4.5 μg/well, and 5.0 μg/well for M1, M2, M3, M4, and M5 receptor membrane preparations, respectively. The assays are conducted at [3H]NMS concentrations approximately equal to the radioligand equilibrium dissociation constant (Kd) for the different muscarinic receptors subtypes. The [3H]NMS concentration is 0.3 nM for the M1 and M4 assays and 1 nM for the M2, M3, and M5 assays. A range of antagonist concentrations (10?14 to 10?5 M) are tested in duplicate to generate competition curves. Nonspecific binding is determined in the presence of atropine (1 μM). Assay reagents are dissolved in assay binding buffer (phosphate-buffered saline with calcium and magnesium) to a total volume of 200 μL. After a 2 hours or 6 hours incubation period (M1–M4 and M5, respectively) at room temperature in 96-well microtiter plates to ensure that equilibrium is achieved for Aclidinium, 150 μL aliquots of the reaction are transferred to GF/C filter plates pretreated for 1 hour with wash buffer (50 mM Tris, 100 mM NaCl, pH 7.4) containing 0.05% polyethylenimine. Bound and free [3H]NMS are then separated by rapid vacuum filtration followed by four washes with ice-cold wash buffer. Filters are then dried for 30 min before addition of 30 μL of OptiPhase Supermix, and radioactivity is quantified using a MicroBeta Trilux microplate scintillation counter. |
| 體外活性 | Aclidinium在所研究的所有物種的血漿樣品中均被水解,37℃下,在大鼠,豚鼠,狗和人的血漿中,表觀半衰期分別為11.7分鐘,38.3分鐘,1.8分鐘和2.4分鐘。0.1 μM Aclidinium抑制人支氣管成纖維細(xì)胞中乙酰膽堿和TGF-β1誘導(dǎo)的Ⅰ型膠原上調(diào),并抑制α-SMA mRNA和蛋白質(zhì)表達(dá)。0.1 μM Aclidinium抑制碳酰膽堿和TGF-β1誘導(dǎo)的人支氣管成纖維細(xì)胞中ERK1/2磷酸化和RhoA-GTP形成的增加。0.1 μM Aclidinium抑制TGF-β1誘導(dǎo)的人支氣管成纖維細(xì)胞中ChAT表達(dá)的上調(diào)。0.1 μM Aclidinium在劑量依賴性地抑制人肺成纖維細(xì)胞的TGF-β1和卡巴膽堿誘導(dǎo)的細(xì)胞增殖。< 100 nM Aclidinium劑量依賴性抑制豚鼠離體豚鼠氣管中卡巴膽堿誘導(dǎo)的收縮。Aclidinium預(yù)處理可阻止人肺成纖維細(xì)胞中M1和M3的上調(diào),但不能抑制由碳酰膽堿或TGF-β1誘導(dǎo)的M2的下調(diào)。 |
| 體內(nèi)活性 | 500 μg/kg Aclidinium給藥1小時(shí)后誘導(dǎo)有意識(shí)的比格犬心率最大增加55%.1 mg/mL Aclidinium在超過(guò)120分鐘的研究期間,產(chǎn)生對(duì)麻醉的豚鼠有效持久的氣管保護(hù)作用(72%–88.4%).在麻醉的豚鼠的乙酰膽堿誘導(dǎo)的支氣管收縮模型中,[3H] AcliAclidinium顯示作用開始,IC50（95％CI）為140 μg/ mL,tmax為30分鐘. |
| 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 : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 104 mg/mL (184.2 mM)
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| 關(guān)鍵字 | inhibit | LAS-34273 | Muscarinic acetylcholine receptor | Aclidinium Bromide | mAChR | Inhibitor | Aclidinium bromide | LAS-W330 | LAS34273 | LAS-W-330 | Aclidinium |
| 相關(guān)產(chǎn)品 | Pilocarpine Hydrochloride | Levamisole hydrochloride | Choline chloride | Pilocarpine nitrate | CLOZAPINE N-OXIDE | Pempidine | Forskolin | (+)-Sparteine | Propoxur | Adiphenine hydrochloride | Ribavirin | Nanofin |
| 相關(guān)庫(kù) | 抑制劑庫(kù) | 經(jīng)典已知活性庫(kù) | 已知活性化合物庫(kù) | EMA 上市藥物庫(kù) | FDA 上市藥物庫(kù) | 臨床期小分子藥物庫(kù) | 膜蛋白靶向化合物庫(kù) | 神經(jīng)退行性疾病化合物庫(kù) | 藥物功能重定位化合物庫(kù) | 表型篩選靶點(diǎn)鑒定庫(kù) |