Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemER406freebaseCat.No.:HY-11108CASNo.:841290-80-0分?式:C??H??FN?O?分?量:470.45作?靶點:Syk;FLT3;Apoptosis作?通路:ProteinTyrosineKinase/RTK;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數據體外實驗DMSO:≥10mg/mL(21.26mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.1256mL10.6281mL21.2562mL5mM0.4251mL2.1256mL4.2512mL10mM0.2126mL1.0628mL2.1256mL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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥0.5mg/mL(1.06mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥0.5mg/mL(1.06mM);ClearsolutionBIOLOGICALACTIVITY?物活性R406freebase?種有效的，具有?服活性的，ATP競爭性的Syk/FLT3抑制劑，Ki為30nM，有效抑制Syk激酶活性，IC50為41nM。R406freebase可減輕免疫復合物介導的炎癥[1]。R406freebase還抑制Lyn(IC50=63nM)和Lck(IC50=37nM)[2].IC50&TargetKi:30nM(Syk)[1]IC50:41nM(Syk)[1]FLT3[1]IC50:63nM(Lyn),37nM(Lck)[2]體外研究R406inhibitsadenosineA3receptor(IC50=0.081μM),adenosinetransporter(IC50=1.84μM),andmonoaminetransporter(IC50=2.74μM)[1].R406inhibitsHuh7hepatocyte,A549epithelial,andH1299lungcancerlineswithEC50sof15.1,2.9and6.3μM,respectively[1].R406inhibitsphosphorylationofSyksubstrateLATinmastcellsandBLNK/SLP65inBcells[1].WesternBlotAnalysis[1]CellLine:Culturedhumanmastcells(CHMC)Concentration:0.016,0.08,0.4,2μMIncubationTime:40minutesResult:Inhibitedallotherkinasestestedat5to100foldlesspotencythanSykasjudgedbyphosphorylationoftargetproteins.體內研究R406(5and10mg/kg)showsefficacyintheameliorationoftheArthusreactionandinreducingclinicalsymptomsinthecollagenantibody-inducedarthritis(CAIA)andK/BxNmodelsofrheumatoidarthritis(RA).Immunecomplex(IC)-mediatedinflammationisreducedbyinhibitionofFcreceptorsignalingwithR406[1].AnimalModel:FemaleBalb/cmice(6-8weeks)withCAIA[1]Dosage:5and10mg/kgAdministration:Administeredorally,b.i.d,for14days,starting4hoursafterantibodychallengeonday0.Result:Reducedinflammationandswelling,andthearthritisprogressedmoreslowlyintreatedanimalsthaninvehiclecontrols.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnimalModel:FemaleC57BL/6micewitharthritis[1]Dosage:10mg/kgAdministration:Administeredorallyonehourbeforeseruminjection;b.i.d;for13daysResult:Delayedtheonsetandreducedtheseverityofclinicalarthritis.Pawthickeningandclinicalarthritiswerereducedbyapproximately50%.戶使?本產品發(fā)表的科研?獻?Cell.2018Oct4;175(2):442-457.e23.?SciTranslMed.2018Jul18;10(450).pii:eaaq1093.?NatCommun.2022Apr19;13(1):2136.?ArthritisRheumatol.2018Sep;70(9):1419-1428.?Theranostics.2021May24;11(15):7308-7321.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].SylviaBraselmann,etal.R406,anorallyavailablespleentyrosinekinaseinhibitorblocksfcreceptorsignalingandreducesimmunecomplex-mediatedinflammation.JPharmacolExpTher.2006Dec;319(3):998-1008.[2].Hoon-SukCha,etal.Anovelspleentyrosinekinaseinhibitorblocksc-JunN-terminalkinase-mediatedgeneexpressioninsynoviocytes.JPharmacolExpTher.2006May;317(2):571-8.McePdfHeightCaution:Pro