Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEBAY-85-8501Cat.No.:HY-19908CASNo.:1161921-82-9分?式:C??H??F?N?O?S分?量:474.46作?靶點(diǎn):Elastase作?通路:MetabolicEnzyme/Protease儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:200mg/mL(421.53mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.1077mL10.5383mL21.0766mL5mM0.4215mL2.1077mL4.2153mL10mM0.2108mL1.0538mL2.1077mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時(shí)，請?jiān)?個?內(nèi)使?，-20°C儲存時(shí)，請?jiān)?個?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥5mg/mL(10.54mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥5mg/mL(10.54mM);Clearsolution3.請依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:2.5mg/mL(5.27mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性BAY-85-8501?類中性脂酶(HNE)的?個有效的、選擇性抑制劑，其IC50值為65pM。IC50&TargetIC50:65pM(HNE)[1].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?ChineseAcademyofSciences.2019Aug.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].VonNussbaumF,etal.FreezingtheBioactiveConformationtoBoostPotency:TheIdentificationofBAY85-8501,aSelectiveandPotentInhibitorofHumanNeutrophilElastaseforPulmonaryDiseases.ChemMedChem.2015Jul;10(7):1163-73.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEMcePdfHeightCaution:Producthasnotbeenfu