Avibactam sodium

SKU: orb1303068

Description

Avibactam sodium (NXL-104) is a reversible covalent inhibitor of β-lactamases, including TEM-1, P99, and KPC-2, with IC50 values of 8, 80, and 38 nM, respectively. It exhibits antimicrobial activity and is utilized in research models of urinary tract infections, both in vitro and in vivo.

Research Area

Infectious Disease & Virology

Key Properties

• CAS Number: 1192491-61-4
• MW: 287.22
• Purity: >99.99% (May vary between batches)
• Formula: C₇H₁₀N₃NaO₆S
• SMILES: [Na+].NC(=O)[C@@H]1CC[C@@H]2CN1C(=O)N2OS([O-])(=O)=O
• Target: Antibacterial,Antibiotic
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (17.41 mM);DMSO:257 mg/mL (894.78 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble);H2O:52 mg/mL (181.05 mM)

Bioactivity

• Target IC50:
  P99:80 nM|KPC2:38 nM|TEM1:8 nM
• In Vivo:
  Avibactam sodium displays a slow return of activity with an off-rate of 0.045±0.022 min-1, which converts to a residence time half-life (tt1/2) of 16±8 min. Avibactam has slow deacylation through hydrolysis or reversibility, and this is in contrast to previously reported extremely long t1/2 values of >1 or >7 d for Avibactam inhibition of TEM-1. Mice are infected with ca.106 CFU of Pseudomonas aeruginosa intramuscularly into the thigh or intranasally to cause pneumonia and are given 8 different (single) subcutaneous doses of Ceftazidime and Avibactam in various combined concentrations, ranging from 1 to 128 mg/kg of body weight in 2-fold increases. The mean estimated half-life in plasma of Ceftazidime in the terminal phase is 0.28 h (SD, 0.02 h), and that of Avibactam is 0.24 h (SD, 0.04 h). Volumes of distribution are 0.80 L/kg (SD, 0.14 L/kg) and 1.18 liters/kg (SD, 0.34 L/kg), respectively.
• In Vitro:
  METHODS: Breast cancer cell lines were treated with (E/Z)-4-Hydroxytamoxifen for 4 h and cell growth was detected. RESULTS: (E/Z)-4-Hydroxytamoxifen was able to inhibit the growth of four breast cancer cell lines, MCF-7, MCF-7/Adr, MDA-MB-231 and MDA-MB-435, with IC50s of 300 nM, 40,000 nM, 30,000 nM and 20,000 nM, respectively. METHODS: HepG2 or MCF-7 cells were incubated with (E/Z)-4-Hydroxytamoxifen (5-50 µM) in labeled medium for 18 h. Kinetic parameters of human SULT-catalyzed sulfation were determined. RESULTS: (E/Z)-4-Hydroxytamoxifen can be metabolized by sulfation in HepG2 and MCF-7 cells.
• Cell Research:
  Avibactam is prepared in sterile water.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.
• Animal Research:
  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.

Storage & Handling

• Storage: keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Pseudomonas aeruginosa, TEM-1, TEM-1 β-lactamases, β-lactamase, KPC-2 β-lactamases, Klebsiella pneumonia, P99 β-lactamases, inhibit, NXL 104, NXL104, NXL-104, Inhibitor, AVE-1330A, Avibactam, Avibactam sodium, Bacterial, antibacterial, Antibiotic, CTX-M-15

Compound Identifiers

PubChem CID

24944097