BAY-85-8501-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBAY-85-8501Cat.No.:HY-19908CASNo.:1161921-82-9分⼦式:C₂₂H₁₇F₃N₄O₃S分⼦量:474.46作⽤靶点:Elastase作⽤通路:MetabolicEnzyme/Protease储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:200mg/mL(421.53mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1077mL10.5383mL21.0766mL5mM0.4215mL2.1077mL4.2153mL10mM0.2108mL1.0538mL2.1077mL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,6months;-20°C,1month。-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。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥5mg/mL(10.54mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥5mg/mL(10.54mM);Clearsolution3.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:2.5mg/mL(5.27mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性BAY-85-8501⼈类中性脂酶(HNE)的⼀个有效的、选择性抑制剂，其IC50值为65pM。IC50&TargetIC50:65pM(HNE)[1].体内研究InthismodeltheexogenousHNEnoxaistheprimarycauseofinjuryandlunghemorrhage.BasedonpicomolarpotencyagainstHNEaswellassingledigitpotencyversusMNE,BAY-85-8501(29)completelypreventsthedevelopmentoflunginjuryandsubsequentinflammationwhenadministered1hpriortotheHNEnoxa.Inthe0.01mg/kgdosegroup,hemoglobinconcentrationisalreadysignificantlydecreased.Atadoseof0.1mg/kg,asignificanteffectonneutrophilcountisobserved.Inthissetup,efficacyispredominantlydrivenbypotencyagainstHNE(Ki=0.08nM).AsthehighlyHNE-selectiveinhibitorBAY85-8501hasnoeffectonPPE,BAY-85-8501couldnotpreventtheprimarylunginjuryinthissetup.Nevertheless,BAY-85-8501couldinhibitMNE,theendogenousdriverofinflammationandsecondaryinjury,althoughwithdecreasedpotency.Consequently,theeffectsofBAY-85-8501oninflammationandsecondaryinjuryareweakeratthispoint,andonlyobservedat30-foldhigherdoses.EfficacyispredominantlydrivenbypotencyagainstMNE(Ki=6nM)inthissecondsetup[1].PROTOCOLAnimalMice[1]Administration[1]Elastaseinducedlungfailureinmice,ratsorhamstersisawidelyusedanimalmodelofacutelungfailure.Theanimalsaretreated1hourpriortoorotrachealinstillationofhumanneutrophilelastase(HNE)orporcinepancreaticelastase(PPE).Inthisstudy,eachmousereceivesBAY-85-8501withdifferentconcentrations(0.003,0.01,0.03,0.1,0.3,3,10,30mg/kg)byP.O.[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•ChineseAcademyofSciences.2019Aug.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].VonNussbaumF,etal.FreezingtheBioactiveConformationtoBoostPotency:TheIdentificationofBAY85-8501,aSelectiveandPotentInhibitorofHumanNeutrophilElastaseforPulmonaryDiseases.ChemMedChem.2015Jul;10(7):1163-73.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEMcePdfHeightCaution:Producthasnotbeenfu