Conteltinib-CT-707-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEConteltinibCat.No.:HY-109084CASNo.:1384860-29-0Synonyms:CT-707分⼦式:C₃₂H₄₅N₉O₃S分⼦量:635.82作⽤靶点:FAK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:31.25mg/mL(49.15mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.5728mL7.8639mL15.7277mL5mM0.3146mL1.5728mL3.1455mL10mM0.1573mL0.7864mL1.5728mL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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.08mg/mL(3.27mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(3.27mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.27mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Conteltinib(CT-707)⼀种多激酶抑制剂，可靶向作⽤于FAK，ALK和Pyk2。Conteltinib(CT-707)对FAK具有显的抑制作⽤，IC50为1.6nM[1]。IC50&TargetIC50:1.6nM(FAK)[1]体外研究Conteltinib(CT-707)synergizeswithXL184tosuppresshepatocellularcarcinomabyblockingXL184-inducedFAKactivation[1].ThecombinationofXL184(5μM)andConteltinib(3μM)significantlyreducesthesurvivalfraction,comparedwitheachagentalone[1].ThecombinationofXL184(5μM)andConteltinib(3μM)resultsinenhancedcaspase-dependentapoptosisinhumanhepatocellularcarcinomacelllines[1].TheFAKphosphorylationinducedbyXL184(5μM)mightbeinvolvedinthesynergisticantitumoreffectofConteltinib(3μM)andXL184[1].CellViabilityAssay[1]CellLine:ThehumanhepatocellularcarcinomacelllinesHepG2andBel-7402Concentration:1.0,1.5,2.0,2.5,and3.0μMforHepG2cells;0.2,0.4,0.8,1.5,and3.0μMforBel-7402cellsIncubationTime:72hoursResult:WhencellswereexposedtoXL184(5μM),Conteltinib(3μM),ortheircombination,thesurvivalrateswere57.3%,39.3%,and11.2%,respectively,inHepG2;thoseinBel-7402were57.8%,61.6%,and34.2%,respectively.ApoptosisAnalysis[1]CellLine:HepG2andBel-7402cellsConcentration:3μMIncubationTime:48hoursResult:Theapoptosisratesofcontrol,XL184,Conteltinib,andcombinationgroupsinHepG2were5.0%,10.5%,18.4%,and41.1%,respectively,andthoseinBel-7402were4.4%,16.3%,8.7%,and36.4%,respectively.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEWesternBlotAnalysis[1]CellLine:HepG2andBel-7402Concentration:3μMIncubationTime:24hoursResult:CouldmarkedlydecreaseFAKphosphorylationinducedbyXL184,whichmightpartiallyaccountforthesynergeticeffect.体内研究ThecombinationofXL184(20mg/kgoncedailyforfirst3days;i.g.10mg/kgonceadayfor4thday;noadministrationfrom5thto10thdays;i.g.10mg/kgonceadayfromthe10thto14thdays)andCT-707(i.g.50mg/kgtwiceadayforfirst3days,7th,8th,11th,12th,and14thdays;onceadayfor4th,6th,9th,10th,and13thdays;noadministrationforthe5thday)showsthesynergisticantitumoreffectinHepG2xenograftnudemice[1].AnimalModel:NudemicetransplantedwithHepG2xenografts[1]Dosage:50mg/kgAdministration:Intragastrically(i.g.)twiceadayforfirst3days,7th,8th,11th,12th,and14thdays;onceadayfor4th,6th,9th,10th,and13thdays;noadministrationforthe5thday.Result:Causedamoderatedecreaseintherelativetumorvolume(RTV).Theinhibitionrateofcombinationgroupreached77.4%,whereasthemono-treatmentofXL184orCT-707alonecaused30.7%and19.4%inhibitioninthetumorweight,respectively.REFERENCES[1].WangDD,etal.CT-707,aNovelFAKInhibitor,SynergizeswithXL184toSuppressHepatocellularCarcinomabyBlockingXL184-InducedFAKActivation.MolCancerTher.2016Dec;15(12):2916-2925.McePd