TAK-659-hydrochloride-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETAK-659hydrochlorideCat.No.:HY-100867ACASNo.:1952251-28-3分?式:C??H??ClFN?O分?量:380.85作?靶點:Syk;FLT3作?通路:ProteinTyrosineKinase/RTK儲存?式:4°C,storedundernitrogen,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen,awayfrommoisture)溶解性數(shù)據(jù)體外實驗DMSO:<1mg/mL(insolubleorslightlysoluble)H2O:2mg/mL(5.25mM;ultrasonicandadjustpHto3withHCl)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.6257mL13.1285mL26.2571mL5mM0.5251mL2.6257mL5.2514mL10mM---------請根據(jù)產(chǎn)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(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month(storedundernitrogen,awayfrommoisture)。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。BIOLOGICALACTIVITY?物活性TAK-659hydrochloride?種?效選擇性、可逆的，?服有效的SYK/FLT3雙抑制劑，對SYK和FLT3作?的IC50值分別為3.2nM、4.6nM。TAK-659hydrochloride能誘導(dǎo)腫瘤細胞死亡?不作?于?腫瘤細胞，具有研究慢性淋巴細胞??病(CLL)的潛?。IC50&TargetIC50:3.2nM(Syk),4.6nM(FLT3)[1]1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE體外研究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.體內(nèi)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?邊的抑制劑?師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