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Medchemexpress/Aprotinin/HY-P0017/10mM*1mL in Water
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AprotininisaserineproteaseinhibitorisolatedfrombovinelungwhichinhibitstrypsinandchymotrypsinwithKivaluesof0.06pMand9nM,respectively.

CustomerValidation

  • AmJPhysiolCellPhysiol.2017Sep13:ajpcell.00006.2017.
Description

AprotininisaserineproteaseinhibitorisolatedfrombovinelungwhichinhibitstrypsinandchymotrypsinwithKivaluesof0.06pMand9nM,respectively.

IC50&Target

Ki:0.06pM(Trypsin),9nM(Chymotrypsin)[1]

InVitro

Aprotinin,aserineproteaseinhibitorisolatedfrombovinelung,isacomplexproteaseinhibitorthatisanantifibrinolytic,inhibitscontactactivation,anddecreasestheinflammatoryresponsetocardiopulmonarybypass[2].Aprotinininhibitstrypsin(bovine,Ki=0.06pM),chymotrypsin(bovine,Ki=9nM),plasmin(human,0.23nM)[1].AprotininisalsoacompetitiveproteininhibitorofNOSactivity.ItinhibitsNOS-IandNOS-IIwithKivaluesof50μMand78μM,respectively[3].AprotininsignificantlyinhibitsfibrinolysiswithanIC50of0.16±0.05μM[4].

InVivo

Highdoseaprotinincanreducebloodlossandtransfusionrequirementsassociatedwithprimarycardiacproceduressuchascoronaryarterybypassgraft(CABG)orheartvalvereplacementsurgery[5].Aprotinininhibitsthrombusformationinadose-dependentmanner.Aprotininatadoseof1.5mgkg-1(bolus)and3mgkg-1h-1infusion(maintenanceinfusion)causesatendencytowardsareductioninbleedingtime.Aprotininsignificantlyreducesthebleedingtimestartingatadoseof3mgkg-1bolusplus6mgkg-1h-1showingareductionofapproximately84%±2.9%.Atthehighestdoseof5mgkg-1and10mgkg-1h-1,thestrongesteffectsareobserved[4].Aprotininmayaffecttumornecrosisfactor-alpha(TNF)levels.SolubleTNFRIlevelsaresignificantlyincreasedfollowingI/RintheaprotinintreatedwildtypemiceandnotdetectedinallTNFRInullmice[6].

ClinicalTrial
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References
  • [1].FritzH,etal.Biochemistryandapplicationsofaprotinin,thekallikreininhibitorfrombovineorgans.Arzneimittelforschung.1983;33(4):479-94.

    [2].LevyJH,etal.Efficacyandsafetyofaprotininincardiacsurgery.Orthopedics.2004Jun;27(6Suppl):s659-62.

    [3].VenturiniG,etal.Aprotinin,thefirstcompetitiveproteininhibitorofNOSactivity.BiochemBiophysResCommun.1998Aug10;249(1):263-5.

    [4].SperzelM,etal.Evaluationofaprotininandtranexamicacidindifferentinvitroandinvivomodelsoffibrinolysis,coagulationandthrombusformation.JThrombHaemost.2007Oct;5(10):2113-8.Epub2007Jul31.

    [5].DavisR,etal.Aprotinin.Areviewofitspharmacologyandtherapeuticefficacyinreducingbloodlossassociatedwithcardiacsurgery.Drugs.1995Jun;49(6):954-83.

    [6].SabbaghMJ,etal.Aprotininexacerbatesleftventriculardysfunctionafterischemia/reperfusioninmicelackingtumornecrosisfactorreceptorI.JCardiovascPharmacol.2008Oct;52(4):355-62.

AnimalAdmiNISTration
[4][6]

Rat:MaleWistarrats(180-220g)areusedinthestudy.Aprotininisdissolvedinphysiologicalsaline.Aprotininisadministeredbybolusinjectionfollowedbyamaintenanceinfusion.Thedosesgivenare1.5mgkg-1and3mgkg-1h-1,3mgkg-1and6mgkg-1h-1upto5mgkg-1and10mgkg-1h-1.Plasmaconcentrationsforthetwoagentsareassessedbypharmacokineticstudiesinrats[4].

Mouse:Anintactmousemodelofischemia/reperfusion(30min-I/60min-R)isusedandleftventricularpeak+dP/dtismeasuredinwildtypemice(WT,C57BL/6;n=10),WTmicewithaprotinin(4mL/kg;n=10),transgenicmicedevoidoftheTNFRI(TNFRInull;n=10),andTNFRInullwithaprotinin(n=10)[6].

MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References
  • [1].FritzH,etal.Biochemistryandapplicationsofaprotinin,thekallikreininhibitorfrombovineorgans.Arzneimittelforschung.1983;33(4):479-94.

    [2].LevyJH,etal.Efficacyandsafetyofaprotininincardiacsurgery.Orthopedics.2004Jun;27(6Suppl):s659-62.

    [3].VenturiniG,etal.Aprotinin,thefirstcompetitiveproteininhibitorofNOSactivity.BiochemBiophysResCommun.1998Aug10;249(1):263-5.

    [4].SperzelM,etal.Evaluationofaprotininandtranexamicacidindifferentinvitroandinvivomodelsoffibrinolysis,coagulationandthrombusformation.JThrombHaemost.2007Oct;5(10):2113-8.Epub2007Jul31.

    [5].DavisR,etal.Aprotinin.Areviewofitspharmacologyandtherapeuticefficacyinreducingbloodlossassociatedwithcardiacsurgery.Drugs.1995Jun;49(6):954-83.

    [6].SabbaghMJ,etal.Aprotininexacerbatesleftventriculardysfunctionafterischemia/reperfusioninmicelackingtumornecrosisfactorreceptorI.JCardiovascPharmacol.2008Oct;52(4):355-62.

MolecularWeight

6511.44

Formula

C₂₈₄H₄₃₂N₈₄O₇₉S₇

CASNo.

9087-70-1

Storage
Powder-80°C2years
 -20°C1year
Insolvent-80°C6months
 -20°C1month
Shipping

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

H2O:≥100mg/mL

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

Purity:99.56%