R406-free-base-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemER406freebaseCat.No.:HY-11108CASNo.:841290-80-0分⼦式:C₂₂H₂₃FN₆O₅分⼦量:470.45作⽤靶点:Syk;FLT3;Apoptosis作⽤通路:ProteinTyrosineKinase/RTK;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥10mg/mL(21.26mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1256mL10.6281mL21.2562mL5mM0.4251mL2.1256mL4.2512mL10mM0.2126mL1.0628mL2.1256mL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.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥0.5mg/mL(1.06mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥0.5mg/mL(1.06mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性R406freebase⼀种有效的，具有⼝服活性的，ATP竞争性的Syk/FLT3抑制剂，Ki为30nM，有效抑制Syk激酶活性，IC50为41nM。R406freebase可减轻免疫复合物介导的炎症[1]。R406freebase还抑制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]体外研究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.体内研究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—您⾝边的抑制剂⼤师www.MedChemEAnimalModel:FemaleC57BL/6micewitharthritis[1]Dosage:10mg/kgAdministration:Administeredorallyonehourbeforeseruminjection;b.i.d;for13daysResult:Delayedtheonsetandreducedtheseverityofclinicalarthritis.Pawthickeningandclinicalarthritiswerereducedbyapproximately50%.户使⽤本产品发表的科研⽂献•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