Tizaterkib-AZD0364-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETizaterkibCat.No.:HY-111483CASNo.:2097416-76-5Synonyms:AZD0364分⼦式:C₂₄H₂₄F₂N₈O₂分⼦量:494.5作⽤靶点:ERK作⽤通路:MAPK/ERKPathway;StemCell/Wnt储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥100mg/mL(202.22mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.0222mL10.1112mL20.2224mL5mM0.4044mL2.0222mL4.0445mL10mM0.2022mL1.0111mL2.0222mL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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.21mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Tizaterkib(AZD0364)⼀种有效的选择性ERK2抑制剂，IC50为0.6nM。详细信息请参考专利⽂献WO2017080979A1中的化合物example18。IC50&TargetERK20.6nM(IC50)体外研究TizaterkibismeasuredintheERK2massspectrometryandA375phospho-p90RSKassayswithIC50sof0.6nMand5.7nM,respectively.Tizaterkibcaninhibitthegrowthofapanelofcancercelllines(A549,H2122,H2009,andCalu6celllines)withKRASmutationsasamonotherapyandthiseffectissynergisticallyenhancedbytreatmentwithSelumetinib[1].体内研究TumorgrowthinhibitionbyTizaterkibethanesulfonicacid(Example18a)incombinationwithMEKinhibitorSelumetinibismeasured.StudiesareperformedintheA549xenograftmodel.Selumetinibisdosedtwicedaily(BiD)8hoursapartandTizaterkibethanesulfonicacidisdosedoncedaily(QD)4hoursafterthefirstSelumetinibdose.Bothcompoundsaredosedcontinuouslyfor3weeks.Bothvehiclesaredosedinthevehiclegroup.BothSelumetinibandTizaterkibethanesulfonicacidreducetumorgrowthrelativetovehicleonlycontrol.ThecombinationofSelumetinibandTizaterkibethanesulfonicacidresultsinareductionintumorgrowth[1].PROTOCOLCellAssay[1]KRAS-mutantNon-SmallCellLungCancer(NSCLC)A549,H2122,H2009,andCalu6celllinesareseededin384-wellblack,clearbottomedplates,culturedfor18-24hoursandtreatedwithincreasingconcentrationsofAZD-0364(7.143nM,61nM,357nM,2.143μMand10μM)andSelumetinib(0-10μM)ina6×6dosingmatrix.Cellsareseededataconcentrationsuchthatcellsinuntreatedwellsareapproximately80%confluentattheendoftheassay.After3daysoftreatment,livecellnumberisdeterminedusingaSytoxGreenendpoint[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]A549isahumannonsmallcelllungcancerlinecarryinganoncogenicmutationintheKRASgene(G12S).Femalenudemiceareimplantedsubcutaneously(s.c.)ontheleftflank,with5×106A549cells(ATCC)permouse.Tumorgrowthismonitoredbytwiceweeklycallipermeasurementandvolumesarecalculated.Oncetumorshavereachedavolumeof~200-300mm3animalsarerandomisedintogroupsof7-11andaretreatedwithacontinuouscombinationscheduleofSelumetinib(ARRY-142886)25mg/kgBiDandAZD-0364ethanesulfonicacid25mg/kgQD(fourhoursafterfirstSelumetinibdose),botharedosedbyperoralroute.Tumorvolumesaremeasuredtwiceweeklyafterdosingcommenced[1].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEMCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•VetMicrobiol.2021,109061.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].WARD,Richard,Andrew,etal.DIHYDROIMIDAZOPYRAZINONEDERIVATIVESUSEFULINTHETREATMENTOFCANCER.WO2017080979A1.McePdfHeightCau