Dovitinib-lactate-CHIR-258-lactate-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEDovitiniblactateCat.No.:HY-10207CASNo.:692737-80-7Synonyms:CHIR-258lactate;TKI-258lactate分⼦式:C₂₄H₂₇FN₆O₄分⼦量:482.51作⽤靶点:FLT3;c-Kit;FGFR;VEGFR;PDGFR作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:≥30mg/mL(62.17mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.0725mL10.3625mL20.7250mL5mM0.4145mL2.0725mL4.1450mL10mM0.2072mL1.0362mL2.0725mL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(sealedstorage,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Dovitiniblactate(TKI258lactate)多靶点的酪氨酸激酶抑制剂，抑制FLT3，c-Kit，FGFR1/3，VEGFR1/2/3和PDGFRα/β的IC50值分别为1，2，8/9，10/13/8，27/210nM[1]。IC50&TargetFGFR3FGFR1VEGFR1VEGFR21/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE9nM(IC50)8nM(IC50)1nM(IC50)13nM(IC50)VEGFR3PDGFRαPDGFRβFLT38nM(IC50)27nM(IC50)210nM(IC50)1nM(IC50)c-Kit2nM(IC50)体外研究DovitinibpotentlyinhibitstheFGF-stimulatedgrowthofWTandF384L-FGFR3-expressingB9cellswithIC50valuesof25nM.B9-MINVcellsareresistanttotheinhibitoryactivityofDovitinibatconcentrationsupto1μM.DovitinibinhibitscellproliferationofKMS11(FGFR3-Y373C),OPM2(FGFR3-K650E),andKMS18(FGFR3-G384D)cellswithIC50ofvaluesof90nM(KMS11andOPM2)and550nM,respectively[1].TreatmentofSK-HEP1cellswithdovitinibresultsinG2/Mcellcyclearrest,inhibitionofcolonyformationinsoftagarandblockadeofbFGF-inducedcellmigration.DovitinibinhibitsbasalexpressionandFGF-inducedphosphorylationofFGFR-1,FRS2-αandERK1/2[2].体内研究Dovitinib(10mg/kg,30mg/kg,60mg/kg,p.o.)showssignificantantitumoreffectintheKMS11-bearingmicemodel,andthegrowthinhibitionis48%,78.5%,and94%inthe10mg/kg,30mg/kg,and60mg/kgtreatmentarms,respectively,comparedwiththeplacebo-treatedmice[1].DovitinibdemonstratessignificantantitumorandantimetastaticactivitiesinHCCxenograftmodels.DovitinibpotentlyinhibitstumorgrowthofsixHCClines.InhibitionofangiogenesiscorrelateswithinactivationofFGFR/PDGFR-β/VEGFR-2signalingpathways.Dovitinibalsocausesdephosphorylationofretinoblastoma,upregulationofp-histoneH2A-Xandp27,anddownregulationofp-cdk-2andcyclinB1,whichresultsinareductionincellularproliferationandtheinductionoftumorcellapoptosis[2].PROTOCOLCellAssay[2]TodetermineIC50forSK-HEP1cells,cellsareplatedatadensityof2×104cellsperdish.After48h,cellsaretreatedwith0,0.01,0.1,1,5,10,50,100μMdovitinibinDMEMcontaining1%FBSfor24h.CellviabilityisdeterminedwithCellProliferationAssay.IC50iscalculatedbynonlinearregressionanalysisusingGraphPadPrismsoftware[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:SixHCClines(06-0606,26-0808A,26-1004,25-0705A,5-1318,21-0208)areusedtoestablishtumorsAdministration[2]inmaleSCIDmice.ordose-esponseexperiments,micebearingthe06-0606xenograftsreorallygivenvehicle(5%dextrose)ortwodosesofdovitinib(50and75mg/kg)dailyfor14days.Fortime-dependentinhibitionofdovitinibtargets,micebearing06-0606tumorsaregivenorally200μLofeithervehicle(n=6)or50mg/kg/dayofdovitinib(n=10)[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•Theranostics.2018Jul30;8(15):4262-4278.•NPJPrecisOncol.2021Jul16;5(1):66.•FrontCellDevBiol.2020May7;8:287.•BiochemistryforHealth,NOVAUniversityofLisbon.2019Jul.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].TrudelS,etal.CHIR-258,anovel,multitargetedtyrosinekinaseinhibitorforthepotentialtreatmentoft(4;14)multiplemyeloma.Blood.2005,105(7),2941-2948.[2].HuynhH,etal.Dovitinibdemonstratesantitumorandantimetastaticactivitiesinxenograftmodelsofhepatocellularcarcinoma.JHepatol.2012,56(3)