TAK-659-hydrochloride-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETAK-659hydrochlorideCat.No.:HY-100867ACASNo.:1952251-28-3分⼦式:C₁₇H₂₂ClFN₆O分⼦量:380.85作⽤靶点:Syk;FLT3作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:4°C,storedundernitrogen,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen,awayfrommoisture)溶解性数据体外实验DMSO:<1mg/mL(insolubleorslightlysoluble)H2O:2mg/mL(5.25mM;ultrasonicandadjustpHto3withHCl)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.6257mL13.1285mL26.2571mL5mM0.5251mL2.6257mL5.2514mL10mM---------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(storedundernitrogen,awayfrommoisture)。-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。BIOLOGICALACTIVITY⽣物活性TAK-659hydrochloride⼀种⾼效选择性、可逆的，⼝服有效的SYK/FLT3双抑制剂，对SYK和FLT3作⽤的IC50值分别为3.2nM、4.6nM。TAK-659hydrochloride能诱导肿瘤细胞死亡⽽不作⽤于⾮肿瘤细胞，具有研究慢性淋巴细胞⽩⾎病(CLL)的潜⼒。IC50&TargetIC50:3.2nM(Syk),4.6nM(FLT3)[1]1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE体外研究TAK-659hydrochlorideinhibitscellularproliferationinSYK-dependentDLBCLandFLT3-dependentAMLcelllines[1][3].TAK-659hydrochloride(5µM;1-24hours)inducesCasp3activationintheLMP2A/MYCcellswhichwasreadilyapparentat4handreachedmaximumlevelsat8hoftreatment[4].TAK-659hydrochloride(0.01-10μM;1hour)stimulatesexpressionofphospho-SykatTyr525andTyr352andphospho-ERK1/2increasedinRamoscells[2].ApoptosisAnalysis[4]CellLine:LMP2A/MYCcellsConcentration:5µMIncubationTime:1hour,2hours,4hours,8hours,24hoursResult:InducedapoptosisinLMP2A/MYClymphomacells.WesternBlotAnalysis[2]CellLine:RamoscellsConcentration:0.01μM,0.1μM,1μM,10μMIncubationTime:1hourResult:Enhancedexpressionofphospho-SykatTyr525andTyr352andphospho-ERK1/2instimulatedRamoscells.体内研究TAK-659hydrochloride(100mg/kg/day;p.o.;daily,for10days)treatmenttotallyabrogatessplenomegalyandtumordevelopmentinLMP2A/MYCmiceinbothpretumorandtumorcelltransferexperiments[4].TAK-659hydrochloridetreatmentkillstumorcells,butnothostcellswithinthespleenandtumors[4].TAK-659hydrochloridetreatmentabrogatesmetastasisoftumorcellsintobonemarrow[4].AnimalModel:LMP2A/MYCdoubletransgenicmice[4]Dosage:100mg/kg/dayAdministration:Oralgavage;for10daysResult:InhibitedLMP2A-inducedtumorcellsurvivalinvivo.REFERENCES[1].LamB,etal.DiscoveryofTAK-659anorallyavailableinvestigationalinhibitorofSpleenTyrosineKinase(SYK).BioorgMedChemLett.2016Dec15;26(24):5947-5950.[2].PurroyN,etal.InhibitionofBCRsignalingusingtheSykinhibitorTAK-659preventsstroma-mediatedsignalinginchroniclymphocyticleukemiacells.Oncotarget.2017Jan3;8(1):742-756.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[3].JieYu,etal.Anti-tumoractivityofTAK-659,adualinhibitorofSYKandFLT-3kinases,inAMLmodels.JournalofClinicalOncology34,no.15_suppl.[4].CenO,etal.SpleenTyrosineKinaseInhibitorTAK-659PreventsSplenomegalyandTumorDevelopmentinaMurineModelofEpstein-BarrVirus-AssociatedLymphoma.mSphere.2018Aug22;3(4).McePdfHeightCaution:Producthasnotbeenfully