GDC-0425-RG-7602-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEGDC-0425Cat.No.:HY-19926CASNo.:1200129-48-1Synonyms:RG-7602分?式:C??H??N?O分?量:321.38作?靶點(diǎn):CheckpointKinase(Chk)作?通路:CellCycle/DNADamage儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)H2O:25mg/mL(77.79mM;ultrasonicandadjustpHto3withHCl)MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.1116mL15.5579mL31.1158mL5mM0.6223mL3.1116mL6.2232mL10mM0.3112mL1.5558mL3.1116mL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。-80°C儲存時(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲存時(shí)，請?jiān)?個(gè)?內(nèi)使?。BIOLOGICALACTIVITY?物活性GDC-0425(RG-7602)?種有效的、具有?服活性的、?選擇性的ChK1抑制劑。GDC-0425可?于多種惡性腫瘤的研究[1][2]。IC50&TargetChk11/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE體外研究MEKinhibitioneitherbypharmacologicinhibitorsorRNAi-mediatedgenesilencingsignificantlyprotectedcellsfromreducedviabilityuponGDC-0425treatment[3].GDC-0425(3μM;24hours)treatmentresultsthehyperphosphorylationofChk1[3].CellViabilityAssay[3]CellLine:Chk1-positivebreastcancercelllinesConcentration:0.001,0.01,0.1,1,10mMIncubationTime:72hoursResult:Reducedcellproliferation.CellViabilityAssay[3]CellLine:U-2OScellsConcentration:3μMIncubationTime:24hoursResult:LedtohyperphosphorylationofChk1.體內(nèi)研究GDC-0425exhibitspartialsuppressionoftumorgrowth.TheGemcitabine/GDC-0425combinationresultsinsignificanttumorregressioninalltestedmodels[3].AnimalModel:NCrnudemicebearingxenograftsofbothosteosarcomaandtriple-negativebreastcancermodels(143BPMLBKTK,HCC1806,andHCC70celllines)[3]Dosage:Forthe4-armstudy,miceweretreatedwithvehicle,Gemcitabine120mg/kg,GDC-042575mg/kgalone,orGemcitabineandGDC-0425combinationfor15days.For6-armstudiesofHCC1806andHCC70models,miceweretreatedwithvehicle,Gemcitabine120mg/kg,GDC-042550mg/kg,GDC-042575mg/kgalone,orGemcitabineandGDC-0425combination.Administration:Orallyadministratedat24,48,and72hoursaftergemcitabineadministrationbyintraperitonealinjection.Result:ExhibitedpartialsuppressionoftumorgrowthupontreatmentwitheitherGemcitabineorGDC-0425alone.Notably,theGemcitabine/GDC-0425combinationresultedinsignificanttumorregressioninalltestedmodels.REFERENCES[1].XiaoDing,etal.AsupportedliquidextractionLC-MS/MSmethodfordeterminationofconcentrationsofGDC-0425,asmallmoleculeCheckpointkinase1inhibitor,inhumanplasma.BiomedChromatogr.2016Dec;30(12):1984-1991.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[2].JeffreyRInfante,etal.PhaseIStudyofGDC-0425,aCheckpointKinase1Inhibitor,inCombinationwithGemcitabineinPatientswithRefractorySolidTumors.ClinCancerRes.2017May15;23(10):2423-2432.[3].Ho-JuneLee,etal.Ras-MEKSignalingMediatesaCriticalChk1-DependentDNADamageResponseinCancerCells.MolCancerTher.2017Apr;16(4):694-704.McePdfHeightCaution:Producthasnotbeenfullyvalidated