Brensocatib-AZD7986-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBrensocatibCat.No.:HY-101056CASNo.:1802148-05-5Synonyms:AZD7986;INS1007分⼦式:C₂₃H₂₄N₄O₄分⼦量:420.46作⽤靶点:DipeptidylPeptidase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:≥100mg/mL(237.83mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.3783mL11.8917mL23.7835mL5mM0.4757mL2.3783mL4.7567mL10mM0.2378mL1.1892mL2.3783mL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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.95mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.95mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Brensocatib(AZD7986)⼀个⼆肽肽酶1(DPP1)抑制剂，在⼈，⼩⿏，⼤⿏，狗和兔中的pIC50值分别为6.85,7.6,7.7,7.8和7.8[1]。IC50&TargetpIC50:6.85(humanDPP1),7.6(mouseDPP1),7.7(ratDPP1),7.8(dogDPP1),7.8(rabbitDPP1)[1]体外研究ResultsfromcellassayshowthatBrensocatib(AZD7986)isaDipeptidylpeptidase1(DPP1)inhibitorwithpIC50sof6.85,7.6,7.7,7.8,and7.8inhuman,mouse,rat,dogandrabbit,respectively.Brensocatibisstableinthepropionaldehydereactivityassay,withahalf-lifeover50h.AfterdifferentiationinthepresenceofBrensocatib(38pMto10μM),concentration-dependentdecreasesincelllysateenzymeactivityareobservedforDPP1,aswellasforallofthethreeNSPs,NE,Pr3,andCatG.BrensocatibinhibitsactivationofallthreeNSPsinaconcentrationdependentmanner,withpIC50valuesofaround7forallthreeNSPs.Thereductionoftheactivitiesisalmostcomplete,withNE,Pr3,andCatGactivitiesreducedto4to10%ofcontrolat10μMBrensocatib[1].体内研究Brensocatib(AZD7986)showsgoodstabilityinplasma,withahalflifeof>10h.BrensocatibinhibitsactivationofNEandPr3,butnotCatG,inbonemarrowcelllysatesinadosedependentmannerinvivo[1].PROTOCOLCellAssay[1]CellularpotencyisstudiedusingtheDPP1-expressingmonocyticU937cellline.Briefly,cellsgrowninRPMIareplatedon384-wellpolypropylenev-bottomplatesatadensityof5×105cells/mLperwell.Addedtothisis10μLofBrensocatibat37°Cfor60min,followedby350μMGly-Phe-AFC.Thewellfluorescenceisreadusingamultilabelplatereader.DataareanalyzedtocalculatepIC50values[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalRatsareusedfortheinvivostudy.NaiveratsaredosedorallytwicedailywithBrensocatibat0.2,2,and20Administration[1]mg/kg/dayfor8days.Attermination,bonemarrowistakenbyfemuralaspirationforneutrophilserineproteases(NSPs)activityanalysisusingcommercialsyntheticpeptidesubstrates[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CancerCell.2021Mar8;39(3):423-437.e7.•BiochemPharmacol.2019Jun;164:349-367.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESeemorecustomervalidationsonwww.MedChemEREFERENCES[1].DoyleK,etal.DiscoveryofSecondGenerationReversibleCovalentDPP1InhibitorsLeadingtoanOxazepaneAmidoacetonitrileBasedClinicalCandidate(AZD7986).JMedChem.2016Oct27;59(20):9457-9472.McePdfHeightCaution:Pro