BPO-27-racemate-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEBPO-27racemateCat.No.:HY-19778ACASNo.:1314873-02-3分?式:C??H??BrN?O?分?量:548.34作?靶點:CFTR;Autophagy作?通路:MembraneTransporter/IonChannel;Autophagy儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:16.67mg/mL(30.40mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.8237mL9.1184mL18.2369mL5mM0.3647mL1.8237mL3.6474mL10mM0.1824mL0.9118mL1.8237mL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，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?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：(為保證實驗結(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)實驗的?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:1.67mg/mL(3.05mM);Suspendedsolution;Needultrasonic1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1.67mg/mL(3.05mM);ClearsolutionBIOLOGICALACTIVITY?物活性BPO-27racemate有效的CFTR抑制劑，IC50值為8nM。IC50&TargetIC50:8nM[1]體外研究Thebenzopyrimido-pyrrolo-oxazinedioneBPO-27isananalogueofPPQ-102,whichinhibitsCFTRwithanIC50of8nM.TheRenantiomerofBPO-27inhibitsCFTRchlorideconductancewithanIC50of4nM,whileSenantiomerisinactive.Invitrometabolicstabilityinhepaticmicrosomesshowsbothenantiomersasstable,withlessthan5%metabolismin4h[1].(R)-BPO-27bindsnearthecanonicalATPbindingsite.Whole-cellpatch-clampstudiesshowslinearCFTRcurrentswithavoltage-independent(R)-BPO-27blockmechanism.Ataconcentrationof(R)-BPO-27thatinhibitsCFTRchloridecurrentby50%,theEC50forATPactivationofCFTRincreasesfrom0.27to1.77mM[2].體內(nèi)研究Followingbolusinterperitonealadministrationinmice,serum(R)-1decayswitht1/2≈1.6handgivessustainedtherapeuticconcentrationsinkidney[1].PROTOCOLCellAssay[2]Whole-cellrecordingsaredoneonCFTR-expressingCHO-K1cells.Afterestablishingthewhole-cellconfiguration,BPO-27isaddedfor5minutes,andthenCFTRisactivatedbytheadditionofforskolin(10μM)inthecontinuedpresenceofBPO-27(0.5or1μM).Whole-cellcurrentsareelicitedbyapplyinghyperpolarizinganddepolarizingvoltagepulsesfromaholdingpotentialof0mVtopotentialsbetween+80and?80mVinstepsof20mV.RecordingsaremadeatroomtemperatureusinganAxopatch-200B.CurrentsaredigitizedwithaDigidata1440Aconverterandfilteredat5kHz[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:(R)-BPO-27isformulatedat1mg/mLin5%DMSO,2.5%Tween-80and2.5%PEG400inwater.MaleAdministration[1]miceinaCD1geneticbackgroundareadministered300μLofthe(R)-BPO-27formulationbyintraperitonealinjection.Atspecifiedtimes,bloodsamplesarecollectedbyeyebleed.At4h,kidneysareremovedfollowingrenalarterialperfusionwithPBS.Kidneysareweighed,mixedwithaceticacidandhomogenizedforanalysis[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?Gastroenterology.2018Dec;155(6):1883-1897.e10.Seemorecustomervalidationsonwww.MedChemE2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEREFERENCES[1].SnyderDS,etal.AbsoluteConfigurationAndBiologicalPropertiesofEnantiomersofCFTRInhibitorBPO-27.ACSMedChemLett.2013May9;4(5):456-459.[2].KimY,etal.Benzopyrimido-pyrrolo-oxazine-dione(R)-BPO-27InhibitsCFTRChlorideChannelGatingbyCompetitionwithATP.MolPharmacol.2015Oct;88(4):689-96.McePdfHeightCaution: