FLT3-IN-3-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEFLT3-IN-3Cat.No.:HY-112145CASNo.:2229050-90-0分⼦式:C₂₇H₃₈N₈O分⼦量:490.64作⽤靶点:FLT3作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:250mg/mL(509.54mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.0382mL10.1908mL20.3815mL5mM0.4076mL2.0382mL4.0763mL10mM0.2038mL1.0191mL2.0382mL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%salineSolubility:≥2.08mg/mL(4.24mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.24mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.24mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性FLT3-IN-3⼀种有效的FLT3抑制剂，抑制FLT3WT和FLT3D835Y，IC50分别为13和8nM。IC50&TargetIC50:13nM(FLT3WT),8nM(FLT3D835Y)[1]体外研究FLT3-IN-3(Compound7d)inhibitstheproliferationofFLT3-ITDpositiveMV4-11andMOLM-13celllinesveryeffectivelyatlownanomolarconcentrations(GI50values2and1nM,respectively)[1].FLT3-IN-3(1nM,10nM,100nM,1μMand10μM;72hours)inhibitstheBa/F3FLT3-ITDcellswiththeGI50of0.034±0.015μM,andinhibitstheparentalBa/F3cellswiththeGI50valueof1.136±0.389μM[1].Concentrationsaslowas1nMaresufficienttoblocktheautophosphorylationoftheFLT3receptortyrosinekinaseatthreedifferenttyrosineresidues(589,591,and842).Moreover,thisinhibitionsuppressesphosphorylationofseveraldownstreamtargetsofFLT3.Notably,FLT3-IN-3(0.01,0.1,1,10and100nM;1hours)abolishesphosphorylationofSTAT5atY694,whichisadirectsubstrateoftheoncogenicFLT3-ITDvariant.ThesecondpathwayaffectedistheMAPKcascade:Twokeycomponentsofthissignalingpathway,ERK1/2(T202/Y204)andMEK1/2(S217/221),exhibitreducedphosphorylationupontreatmentwithFLT3-IN-3.FLT3-IN-3alsointerferswithPI3K/AKTpathwaywhichisconfirmedbyreducedphosphorylationofAKTatS473[1].CellProliferationAssay[1]CellLine:MurineBa/F3FLT3-ITDandparentalBa/F3cellsConcentration:1nM,10nM,100nM,1μMand10μMIncubationTime:72hoursResult:TheGI50sforBa/F3FLT3-ITDcellsandparentalBa/F3cellsare0.034±0.015μMand1.136±0.389μM,respectively.WesternBlotAnalysis[1]CellLine:MV4-11cellsConcentration:0.01,0.1,1,10and100nMIncubationTime:1hoursResult:Concentrationsaslowas1nMweresufficienttoblocktheautophosphorylationoftheFLT3receptortyrosinekinaseatthreedifferenttyrosineresidues(589,591,and842).2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE体内研究AsingledoseofFLT3-IN-3(Compound7d;10mg/kg;i.p.)inmicewithsubcutaneousMV4-11xenograftscausessustainedinhibitionofFLT3andSTAT5phosphorylationover48hours[1].AnimalModel:Femaleathymicnu/numicewithsubcutaneouslyimplantedMV4-11xenografts[1]Dosage:10mg/kgAdministration:Intraperitoneal(i.p.)injection;48hoursResult:EffectivelyinhibitedFLT3-ITDautophosphorylationinMV4-11xenografts.REFERENCES[1].GuckýT,etal.DiscoveryofN2-(4-Amino-cyclohexyl)-9-cyclopentyl-N6-(4-morpholin-4-ylmethyl-phenyl)-9H-purine-2,6-diamineasaPotentFLT3KinaseInhibitorforAcuteMyeloidLeukemiawithFLT3Mutations.JMedChem.2018May10;61(9):3855-3869.McePdfHeightCaution:P