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当前位置： 首页 > 产品中心 > Small_molecule > Medchemexpress/Avibactam sodium(Synonyms: NXL-104)/HY-14879A/100mg
商品详细Medchemexpress/Avibactam sodium(Synonyms: NXL-104)/HY-14879A/100mg
Medchemexpress/Avibactam sodium(Synonyms: NXL-104)/HY-14879A/100mg
Medchemexpress/Avibactam sodium(Synonyms: NXL-104)/HY-14879A/100mg
商品编号： HY-14879A-10mM*1mLinDMSO
品牌： MedChemExp
市场价： ¥1580.00
美元价： 948.00
产地： 美国(厂家直采)
公司：
产品分类： 小分子
公司分类： Small_molecule
联系Q Q： 3392242852
电话号码： 4000-520-616
电子邮箱： info@ebiomall.com
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商品介绍
Avibactamsodiumisacovalent,reversIBLeβ-lactamaseinhibitor,inhibitsβ-lactamaseTEM-1andCTX-M-15withIC50of8nMand5nM,respectively.
Description

Avibactamsodiumisacovalent,reversibleβ-lactamaseinhibitor,inhibitsβ-lactamaseTEM-1andCTX-M-15withIC50of8nMand5nM,respectively.

IC50&Target

IC50:8nM(TEM-1),5nM(CTX-M-15)[1]

InVitro

Avibactam(NXL104)sodiumisamoleculewithlittleantibacterialactivity,thatinhibitsclassAandCβ-lactamases.Avibactaminactivatesmostimportantβ-lactamasesexceptmetallotypesandAcinetobacterOXAcarbapenemases[2].

InVivo

Avibactamsodiumdisplaysaslowreturnofactivitywithanoff-rateof0.045±0.022min-1,whichconvertstoaresidencetimehalf-life(tt1/2)of16±8min.Themeasuredoff-rateforAvibactamsuggeststhatslowdeacylationthroughhydrolysisorreversibilityisoccurring,anditisincontrasttopreviouslyreportedextremelylongt1/2valuesof>1or>7dforAvibactaminhibitionofTEM-1[1].Avibactamisanewpromisingβ-lactamaseinhibitor,toovercomeresistancecausedbyβ-lactamases.Miceareinfectedwithca.106CFUofPseudomonasaeruginosaintramuscularlyintothethighorintranasallytocausepneumoniaandaregiven8different(single)subcutaneousdosesofCeftazidimeandAvibactaminvariouscombinedconcentrations,rangingfrom1to128mg/kgofbodyweightin2-foldincreases.Themeanestimatedhalf-lifeinplasmaofCeftazidimeintheterminalphaseis0.28h(SD,0.02h),andthatofAvibactamis0.24h(SD,0.04h).Volumesofdistributionare0.80liters/kg(SD,0.14liters/kg)and1.18liters/kg(SD,0.34liters/kg),respectively[3].

References

  • [1].EhmannDE,etal.Avibactamisacovalent,reversible,non-β-lactamβ-lactamaseinhibitor.ProcNatlAcadSciUSA.2012Jul17;109(29):11663-8.

    [2].LivermoreDM,etal.Characterizationofβ-lactamaseandporinmutantsofEnterobacteriaceaeselectedwithceftaroline+avibactam(NXL104).JAntimicrobChemother.2012Jun;67(6):1354-8.

    [3].BerkhoutJ,etal.Pharmacokineticsandpenetrationofceftazidimeandavibactamintoepithelialliningfluidinthigh-andlung-infectedmice.AntimicrobAgentsChemother.2015Apr;59(4):2299-304.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM3.4815mL17.4077mL34.8153mL
5mM0.6963mL3.4815mL6.9631mL
10mM0.3482mL1.7408mL3.4815mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
KinaseAssay
[1]

Ina200μLreactionvolume,1μMTEM-1isincubatedwithandwithout5μMAvibactamfor5minat37°Candsubjectedtotwoultrafiltrationcartridge(UFC)stepstoremoveexcessinhibitor(Ultrafree-0.5withBiomaxmembrane,5-kDacutoff).Centrifugationat10,600×gfor8minisperformedat4°C.Aftereachultrafiltrationstep,20μLretentatearedilutedwith180μLassaybuffertorestoretheoriginalenzymeconcentration.AftertwoUFCtreatments,theamountoffreeAvibactamisquantifiedbyliquidchromotography/MS/MSandfoundtobe<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="" non-ufc-treated="" enzyme,="" and="" loss="" is="" found="" to="" be=""><>[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

CellAssay
[2]

Avibactamispreparedinsterilewater[2].

Cells(~109cfu)fromovernightbrothculturearespreadonMueller-Hintonagarsupplementedwitheither(i)CeftarolineplusAvibactam(1or4mg/L)at1-16×theMICsor(ii)Ceftarolineat1or4mg/LplusAvibactamat1-8×theconcentrationneededtoreducetheCeftarolineMICto1or4mg/L.Coloniesarecountedafterovernightincubationandrepresentativesareretained[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdmiNISTration
[3]

Avibactamisreconstitutedinsterilewatertoastocksolutionof5120mg/LandfurthersolutionispreparedinMueller-Hintonbroth(Mice)[3].

Mice[3]
Avibactamisreconstitutedinsterilewatertoastocksolutionof5,120mg/LandfurthersolutionispreparedinMueller-Hintonbroth.OutbredfemaleCD-1mice,7to8weeksoldandweighing20to25g,areusedintheexperiments.Eightdosecombinationsareused.Forthethigh-infectedanimals,thecombinationsofCeftazidimeandAvibactamare16/4,8/1,64/32,and2/128mg/kg.Forthelung-infectedmice,combinationsof32/16,4/2,128/8,and1/64mg/kgoftherespectiveconstituentsareused.Thesecombinationsarechoseninordertodetectpossiblepharmacokineticinteractionsbetweenthetwocompounds(CeftazidimeandAvibactam)andtocoverawiderangeofdosesofeachcompound.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References

  • [1].EhmannDE,etal.Avibactamisacovalent,reversible,non-β-lactamβ-lactamaseinhibitor.ProcNatlAcadSciUSA.2012Jul17;109(29):11663-8.

    [2].LivermoreDM,etal.Characterizationofβ-lactamaseandporinmutantsofEnterobacteriaceaeselectedwithceftaroline+avibactam(NXL104).JAntimicrobChemother.2012Jun;67(6):1354-8.

    [3].BerkhoutJ,etal.Pharmacokineticsandpenetrationofceftazidimeandavibactamintoepithelialliningfluidinthigh-andlung-infectedmice.AntimicrobAgentsChemother.2015Apr;59(4):2299-304.

MolecularWeight

287.23

Formula

C₇H₁₀N₃NaO₆S

CASNo.

1192491-61-4

Storage
Powder-20°C3years
 4°C2years
Insolvent-80°C6months
 -20°C1month
Shipping

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

DMSO:≥30mg/mL

*"<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">

Purity:99.99%