Avibactam (sodium salt)
(Synonyms: 阿维巴坦钠; NXL-104) 目录号 : GC42883
Avibactam (sodium salt)(NXL104, AVE1330A)是一种共价且可逆的非β-内酰胺类β-内酰胺酶抑制剂，有效抑制β-内酰胺酶TEM-1和CTX-M-15，IC50值分别为8 nM和5 nM。Avibactam对Ambler A类和C类β-内酰胺酶具有活性，并对某些Ambler D类酶也具有一定的活性。
Cas No.:1192491-61-4
Sample solution is provided at 25 µL, 10mM.
Avibactam (sodium salt) (NXL104, AVE1330A) is a covalent, reversible inhibitor of non-β-lactam β-lactamases. It effectively inhibits β-lactamase TEM-1 and CTX-M-15 with IC50 values of 8 nM and 5 nM, respectively. Avibactam is active against Ambler class A and C β-lactamases and also shows activity against certain Ambler class D enzymes. The mechanism of action of Avibactam is the formation of stable, irreversible covalent bonds at the active site of class A or class C beta-lactamases, resulting in permanent inactivation of the enzyme[1-3].
Avibactam (sodium salt) at a fixed concentration of 4 μg/ml dramatically improves the activities of cephalosporins against Enterobacteriaceae resistant to these agents by means of ESBL and AmpC β-lactamases[4-5].
Avibactam (sodium salt) and ceftazidime had bactericidal effects in infected with ceftazidime resistant Pseudomonas aeruginosa mice[6]. The addition of the beta-lactamase inhibitor avibactam (2-256 mg/kg; s.c; twice a day for five days) to ceftazidime restored the efficacy of ceftazidime in a mouse model of acute fatal septicemia in mice[7].
References:
[1]. Ehmann DE, Jahić H, et,al. Avibactam is a covalent, reversible, non-β-lactam β-lactamase inhibitor. Proc Natl Acad Sci U S A. 2012 Jul 17;109(29):11663-8. doi: 10.1073/pnas.1205073109. Epub 2012 Jul 2. PMID: 22753474; PMCID: PMC3406822.
[2]. Bhattacharya S, Bonnet A, et,al. inventors; Novexel SA and Forest laboratories holdings, assignees. Polymorphic and pseudopolymorphic forms of a pharmaceutical compound. International patent WO 042560 A2. 2011 April 14.
[3]. Stachyra T, Péchereau MC, et,al. Mechanistic studies of the inactivation of TEM-1 and P99 by NXL104, a novel non-beta-lactam beta-lactamase inhibitor. Antimicrob Agents Chemother. 2010 Dec;54(12):5132-8. doi: 10.1128/AAC.00568-10. Epub 2010 Oct 4. PMID: 20921316; PMCID: PMC2981269.
[4]. Lagacé-Wiens PR, Tailor F, et,al. Activity of NXL104 in combination with beta-lactams against genetically characterized Escherichia coli and Klebsiella pneumoniae isolates producing class A extended-spectrum beta-lactamases and class C beta-lactamases. Antimicrob Agents Chemother. 2011 May;55(5):2434-7. doi: 10.1128/AAC.01722-10. Epub 2011 Feb 28. PMID: 21357295; PMCID: PMC3088241.
[5]. Sader HS, Castanheira M, et,al. Antimicrobial activity of ceftazidime-avibactam against Gram-negative organisms collected from U.S. medical centers in 2012. Antimicrob Agents Chemother. 2014;58(3):1684-92. doi: 10.1128/AAC.02429-13. Epub 2013 Dec 30. PMID: 24379201; PMCID: PMC3957905.
[6]. Berkhout J, Melchers MJ, et,al. Pharmacokinetics and penetration of ceftazidime and avibactam into epithelial lining fluid in thigh- and lung-infected mice. Antimicrob Agents Chemother. 2015 Apr;59(4):2299-304. doi: 10.1128/AAC.04627-14. Epub 2015 Feb 2. PMID: 25645843; PMCID: PMC4356781.
[7]. Endimiani A, Hujer KM, et,al. Evaluation of ceftazidime and NXL104 in two murine models of infection due to KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother. 2011 Jan;55(1):82-5. doi: 10.1128/AAC.01198-10. Epub 2010 Nov 1. PMID: 21041503; PMCID: PMC3019638.
Avibactam (sodium salt)(NXL104, AVE1330A)是一种共价且可逆的非β-内酰胺类β-内酰胺酶抑制剂，有效抑制β-内酰胺酶TEM-1和CTX-M-15，IC50值分别为8 nM和5 nM。Avibactam对Ambler A类和C类β-内酰胺酶具有活性，并对某些Ambler D类酶也具有一定的活性。Avibactam的作用机制是在A类或C类β-内酰胺酶的活性位点形成稳定的、不可逆的共价键，导致酶永久失活[1-3]。
固定浓度4 μg/ml的Avibactam可通过ESBL和AmpC β-内酰胺酶显著提高头孢菌素对耐药肠杆菌科细菌的活性[4-5]。Avibactam和ceftazidime对耐ceftazidime的铜绿假单胞菌感染小鼠有杀菌作用[6]。在小鼠急性致死性败血症小鼠模型中，加入ceftazidime (2-256 mg/kg; s.c; twice a day for five days)可恢复ceftazidime的疗效[7]。
| Cell experiment [1]: | |
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Cell lines |
K. pneumonia (ESBL-producing) |
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Preparation Method |
The bactericidal activity of cefepime in vitro with or without avibactam at 4 μg/ml was determined by broth microdilution method. |
|
Reaction Conditions |
4 μg/ml |
|
Applications |
Avibactam significantly increased the activity of cefepime against ESBL-producing strains, restoring 100% susceptibility to ESBL-producing organism. |
| Animal experiment [2]: | |
|
Animal models |
CD-1 mice |
|
Preparation Method |
Mice were infected by the intraperitoneal injection of the KPC-producing K. pneumoniae strain resulting in the death of untreated controls within 24 to 48 h.Thirty minutes postinfection, a single subcutaneous dose of ceftazidime with and without avibactam was initiated, and the survival ratio was monitored for 5 days twice a day. |
|
Dosage form |
2-256 mg/kg; s.c; twice a day for five days |
|
Applications |
The addition of avibactam significantly reduced the amount of ceftazidime (CAZ) required to treat systemic infections in mice. |
|
References: |
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| Cas No. | 1192491-61-4 | SDF | |
| 别名 | 阿维巴坦钠; NXL-104 | ||
| 化学名 | sulfuric acid, mono[(1R,2S,5R)-2-(aminocarbonyl)-7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl] ester, monosodium salt | ||
| Canonical SMILES | NC([C@H]1[N@@](C2)C(N(OS([O-])(=O)=O)[C@@H]2CC1)=O)=O.[Na+] | ||
| 分子式 | C7H10N3O6S•Na | 分子量 | 287.2 |
| 溶解度 | 5mg/mL in DMSO, or in DMF | 储存条件 | Store at -20°C |
| General tips | 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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.4819 mL | 17.4095 mL | 34.8189 mL |
| 5 mM | 0.6964 mL | 3.4819 mL | 6.9638 mL |
| 10 mM | 0.3482 mL | 1.7409 mL | 3.4819 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet