Brensocatib-AZD7986-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEBrensocatibCat.No.:HY-101056CASNo.:1802148-05-5Synonyms:AZD7986;INS1007分?式:C??H??N?O?分?量:420.46作?靶點(diǎn):DipeptidylPeptidase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:≥100mg/mL(237.83mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.3783mL11.8917mL23.7835mL5mM0.4757mL2.3783mL4.7567mL10mM0.2378mL1.1892mL2.3783mL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(gè)?內(nèi)使?，-20°C儲存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動(dòng)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)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.95mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.95mM);ClearsolutionBIOLOGICALACTIVITY?物活性Brensocatib(AZD7986)?個(gè)?肽肽酶1(DPP1)抑制劑，在?，??，??，狗和兔中的pIC50值分別為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]體外研究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].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?CancerCell.2021Mar8;39(3):423-437.e7.?BiochemPharmacol.2019Jun;164:349-367.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESeemorecustomervalidationsonwww.MedChemEREFERENCES[1].DoyleK,etal.DiscoveryofSecondGenerationReversibleCovalentDPP1InhibitorsLeadingtoanOxazepaneAmidoacetonitrileBasedClinicalCandidate(AZD7986).JMedChem.2016Oct27;59(20):9457-9472.McePdfHeightCaution:Pro