| 名稱 | Avibactam sodium |
| 描述 | Avibactam sodium (NXL-104) is a non-β-lactam β-lactamase inhibitor that inhibits TEM-1, P99, and KPC-2 β-lactamases (IC50=8/80/38 nM) covalently and reversibly. Avibactam sodium has antimicrobial activity and can be used to treat urinary tract infections. |
| 細(xì)胞實(shí)驗(yàn) | Avibactam is prepared in sterile water[2].Cells (~109 cfu) from overnight broth culture are spread on Mueller-Hinton agar supplemented with either (i) Ceftaroline plus Avibactam (1 or 4 mg/L) at 1-16× the MICs or (ii) Ceftaroline at 1 or 4 mg/L plus Avibactam at 1-8× the concentration needed to reduce the Ceftaroline MIC to 1 or 4 mg/L. Colonies are counted after overnight incubation and representatives are retained[2]. |
| 激酶實(shí)驗(yàn) | In a 200 μL reaction volume, 1 μM TEM-1 is incubated with and without 5 μM Avibactam for 5 min at 37°C and subjected to two ultrafiltration cartridge (UFC) steps to remove excess inhibitor (Ultrafree-0.5 with Biomax membrane, 5-kDa cutoff). Centrifugation at 10,600× g for 8 min is performed at 4°C. After each ultrafiltration step, 20 μL retentate is diluted with 180 μL assay buffer to restore the original enzyme concentration. After two UFC treatments, the amount of free Avibactam is quantified by LC/MS/MS and found to be <5% of the original concentration. Loss of protein during UFC is assessed by measuring TEM-1 activity (on 4,000-fold dilution) in the acyl-enzyme sample compare with a non-UFC-treated enzyme, and loss is found to be <5%[1]. |
| 動物實(shí)驗(yàn) | Avibactam is reconstituted in sterile water to a stock solution of 5,120 mg/L and the further solution is prepared in Mueller-Hinton broth. Outbred female CD-1 mice, 7 to 8 weeks old and weighing 20 to 25 g, are used in the experiments. Eight dose combinations are used. For the thigh-infected animals, the combinations of Ceftazidime and Avibactam are 16/4, 8/1, 64/32, and 2/128 mg/kg. For the Lung-infected mice, combinations of 32/16, 4/2, 128/8, and 1/64 mg/kg of the respective constituents are used. These combinations are chosen in order to detect possible pharmacokinetic interactions between the two compounds (Ceftazidime and Avibactam) and to cover a wide range of doses of each compound. |
| 體外活性 | 方法：產(chǎn) KPC 的肺炎克雷伯菌用 Avibactam sodium (1-64 mg/L) 和 Ceftazidime (0.0625-512 mg/L) 處理，通過 broth microdilution method 測定 MICs。
結(jié)果：CAZ-AVI 易感菌株和 CAZ-AVI 耐藥菌株的 Ceftazidime MIC 值與 Avibactam 濃度的增加幾乎呈對數(shù)線性下降。[1] |
| 體內(nèi)活性 | 方法：為檢測體內(nèi)抗感染活性，將 Avibactam sodium (4-24 mg/kg，每 2 h 到每 12 h) 和 Ceftazidime 皮下注射給綠膿桿菌感染的 CD-1 小鼠。
結(jié)果：給藥 Avibactam q2h 明顯更有效，將 Avibactam 靜效的日劑量降低了 2.7 和 10.1 倍，而兩種方案的給藥間隔中游離藥物濃度保持在 1 mg/L 閾值濃度以上產(chǎn)生抑菌作用的平均百分比相似，平均值為 21.6 (q2h) 和 18.5 (q8h)。[2] |
| 存儲條件 | keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 16.67 mg/mL (58.03 mM)
H2O : 52 mg/mL (181 mM)
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| 關(guān)鍵字 | inhibit | antibacterial | Avibactam | Avibactam sodium | NXL 104 | Antibiotic | Bacterial | TEM-1 | β-lactamase | Inhibitor | Klebsiella pneumonia | Pseudomonas aeruginosa | NXL104 |
| 相關(guān)產(chǎn)品 | Crystal Violet | Dehydroacetic acid sodium | G-418 disulfate | Doxycycline | Methyl anthranilate | Neomycin sulfate | Metronidazole | Dimethyl sulfoxide | EDTA copper(II) disodium salt | Ampicillin sodium | Sulfamethoxazole sodium | Kanamycin sulfate |
| 相關(guān)庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 藥物片段庫 | FDA上市及藥典收錄分子庫 | 高選擇性抑制劑庫 | 非甾體類抗炎化合物庫 | NO PAINS 化合物庫 | FDA 上市藥物庫 | 藥物功能重定位化合物庫 |