Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEDoxofyllineCat.No.:HY-B0004CASNo.:69975-86-6分?式:C??H??N?O?分?量:266.25作?靶點:AdenosineReceptor;Phosphodiesterase(PDE);ReactiveOxygenSpecies作?通路:GPCR/GProtein;MetabolicEnzyme/Protease;Immunology/Inflammation;NF-κB儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數據體外實驗DMSO:50mg/mL(187.79mM;Needultrasonic)H2O:25mg/mL(93.90mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.7559mL18.7793mL37.5587mL5mM0.7512mL3.7559mL7.5117mL10mM0.3756mL1.8779mL3.7559mL請根據產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，避免反復凍融造成的產品失效。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?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據您的實驗動物和給藥?式選擇適當的溶解?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：(為保證實驗結果的可靠性，澄的儲備液可以根據儲存條件，適當保存；體內實驗的?作液，建議您現?現配，當天使?；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沉淀、析出現象，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(9.39mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(9.39mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(9.39mM);Clearsolution4.請依序添加每種溶劑：PBSSolubility:65mg/mL(244.13mM);Clearsolution;Needultrasonicandwarmingandheatto60°CBIOLOGICALACTIVITY?物活性Doxofylline?種?服有效的PDEIV抑制劑，也A1AR拮抗劑。Doxofylline通過抑制線粒體ROS的產?，以及改多種細胞途徑(包括NLRP3-TXNIP炎癥體的激活)來減輕上?細胞的炎癥。Doxophylline可?于哮喘、慢性阻塞性肺病和??管痙攣的研究。IC50&TargetAdenosineA1receptor,phosphodiesteraseIV[1][2][3].體外研究Doxofylline(5,10μM;48h)showspotentprotectionagainstLPS-inducedepithelialinflammationbyreducingPGE2,NOrelease,anddecreasingmitochondrialROSgenerationin16HBEcells[1].Doxofylline(5,10μM;48h)suppressesLPS-inducedexpressionofNADPHoxidasesubunitsandTXNIP16HBEcells[1].Doxofylline(5,10μM;48h)inhibitsLPS-inducedNLRP3inflammasomeactivationandsecretionofIL-1bandIL-18,aswellasmitigatesLPS-mediatedSIRT1reduction[1].Doxofylline(0.1-10μM;15min)significantlyreducesfMLP-inducedleukocytemigrationinBMcells(fMLP:Formyl-Methionyl-Leucyl-Phenylalanine)[2].CellViabilityAssay[1]CellLine:16HBEcellsConcentration:5,10μMIncubationTime:48hResult:WeakenedLPS-inducedNOandPGE2inadose-dependentmanner.Exerteddose-dependentinhibitiononLPS-inducedmitochondrialROSproductionandNADPHoxidasesubunitsexpression.SuppressedLPS-inducedTXNIPexpressionandNLRP3inflammasomeactivationattheproteinlevelinadose-dependentmanner.InhibitedLPS-inducedsecretionofIL-1bandIL-18.CellViabilityAssay[2]CellLine:BMcells(fromnaivemice)2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEConcentration:0.1-10μMIncubationTime:15min(pretreat)Result:NotablysurpressedpositivemigrationofBMcellsinresponsetofMLP.體內研究Doxofylline(0.3,1mg/kg;i.p.;single)inhibitsLPS-inducedinflammationinthelungsofmice[2].Doxofylline(0.3mg/kg;i.p.;pre-treat;single)notablyreducestheadhesionofcellstothevasculartissueandsurpressestheexpressionofLPS-inducedICAM-1invivo[2].AnimalModel:MaleBALB/cmice(6to8-week-old)[2].Dosage:0.3,1mg/kgAdministration:Intraperitonealinjection;single.Result:SignificantlyinhibitedthemigrationofneutrophilsandthereleaseofIL-6andTNF-aintothelunglumen.Increasedthebonemarrowleukocytenumberstolevelssimilartothoseseeninthesaline-treatedgroup.NotablyreducedthenumberofcirculatingleukocytesincomparisontoLPS-treatedmice.Significantlyreducedaccumulationofneutrophilsintheperibronchialarea.AnimalModel:MaleBALB/cmice(6to8-week-old)[2].Dosage:0.3mg/kgAdministration:Intraperitonealinjection;pre-treat;single.Result:Significantlyreducedtheadhesionofcellstothevasculartissue,butnottherollingofcellsalongthevesselwallinmice.SignificantlyreducedtheexpressionofICAM-1inducedbyLPS.REFERENCES[1].JiaoP,etal.Theprotectiveeffectofdoxofyllineagainstlipopolysaccharides(LPS)-inducedactivationofNLRP3inflammasomeismediatedbySIRT1inhumanpulmonarybronchialepithelialcells.ArtifCellsNanomedBiotechnol.2020Dec;48(1):687-694.[2].Riffo-VasquezY,etal.Doxofylline,anovofyllineinhibitslunginflammationinducedbylipopolysacharideinthemouse.PulmPharmacolTher.2014Apr;27(2):170-8.[3].ShuklaD,etal.Doxofylline:apromisingmethylxanthinederivativeforthetreatmentofasthmaandchronicobstructivepulmonarydisease.ExpertOpinPharmacother