Avibactam-sodium-hydrate - Bacterial 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAvibactam sodium hydrateCat. No.: HY-14879B分式: CHNNaOS分量: 305.24作靶点: Bacterial作通路: Anti-infection储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 H2O : 200 mg/mL (655.22 mM)* means soluble, but sat

2、uration unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 3.2761 mL 16.3806 mL 32.7611 mL5 mM 0.6552 mL 3.2761 mL 6.5522 mL10 mM 0.3276 mL 1.6381 mL 3.2761 mL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，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Avibactam钠盐合物是-内酰胺酶抑制剂，具有抗菌活性。IC50 & Target IC50: 8 nM (TEM-1), 5

3、nM (CTX-M-15) 1体外研究 Avibactam (NXL104) is a molecule with little antibacterial activity, that inhibits class A and C -lactamases.Avibactam inactivates most important -lactamases except metallo types and Acinetobacter OXAcarbapenemases 2.1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE体内研究 Avibactam

4、 sodium displays a slow return of activity with an off-rate of 0.0450.022 min-1, which converts to aresidence time half-life (tt1/2) of 168 min. The measured off-rate for Avibactam suggests that slowdeacylation through hydrolysis or reversibility is occurring, and it is in contrast to previously rep

5、ortedextremely long t1/2 values of 1 or 7 d for Avibactam inhibition of TEM-1 1. Avibactam is a new promising-lactamase inhibitor, to overcome resistance caused by -lactamases. Mice are infected with ca.106 CFU ofPseudomonas aeruginosa intramuscularly into the thigh or intranasally to cause pneumoni

6、a and are given 8different (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 ofCeftazidime in the terminal phase is 0.28 h (SD, 0.02 h), and that of Avibac

7、tam is 0.24 h (SD, 0.04 h).Volumes of distribution are 0.80 liters/kg (SD, 0.14 liters/kg) and 1.18 liters/kg (SD, 0.34 liters/kg),respectively 3.PROTOCOLKinase Assay 1 In a 200 L reaction volume, 1 M TEM-1 is incubated with and without 5 M Avibactam for 5 min at 37Cand subjected to two ultrafiltrat

8、ion cartridge (UFC) steps to remove excess inhibitor (Ultrafree-0.5 withBiomax membrane, 5-kDa cutoff). Centrifugation at 10,600 g for 8 min is performed at 4C. After eachultrafiltration step, 20 L retentate are diluted with 180 L assay buffer to restore the original enzymeconcentration. After two U

9、FC treatments, the amount of free Avibactam is quantified by liquidchromotography/MS/MS and found to be 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 Cells (109 cfu) from overnight broth culture are spread on Mueller-Hinton agar supplem

10、ented 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 Avibactamat 1-8 the concentration needed to reduce the Ceftaroline MIC to 1 or 4 mg/L. Colonies are counted afterovernight incubation and representatives are retained 2.MCE has not

11、independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 3Administration 3 Avibactam is reconstituted in sterile water to a stock solution of 5,120 mg/L and further solution is prepared inMueller-Hinton broth. Outbred female CD-1 mice, 7 to 8 weeks old and weigh

12、ing 20 to 25 g, are used in theexperiments. Eight dose combinations are used. For the thigh-infected animals, the combinations ofCeftazidime and Avibactam are 16/4, 8/1, 64/32, and 2/128 mg/kg. For the lung-infected mice, combinationsof 32/16, 4/2, 128/8, and 1/64 mg/kg of the respective constituent

13、s are used. These combinations are chosenin order to detect possible pharmacokinetic interactions between the two compounds (Ceftazidime andAvibactam) and to cover a wide range of doses of each compound.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使

14、本产品发表的科研献 J Antimicrob Chemother. 2017 Jul 1;72(7):1930-1936. J Antimicrob Chemother. 2017 Sep 1;72(9):2483-2488.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE J Infect Dis. 2019 Mar 29. pii: jiz128. Antimicrob Agents Chemother. 2019 Jul 15. pii: AAC.01374-19. Antimicrob Agents Chemother. 2018 De

15、c 21;63(1). pii: e01809-18.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Ehmann DE, et al. Avibactam is a covalent, reversible, non-lactam -lactamase inhibitor. Proc Natl Acad Sci U S A. 2012 Jul17;109(29):11663-8.2. Livermore DM, et al. Characterization of -lactamase and porin mutants of Enterobacteriaceae selected with ceftaroline + avibactam(NXL104). J Antimicrob Chemother. 2012 Jun;67(6):1354-8.3. Berkhout J, et al. Pharmacokinetics and penetration of ceftazidime and avibactam into epithelial lining fluid in thigh- and lung-infectedmice. Antimicrob Age