PHY34-DataSheet-生命科學(xué)試劑-MCE

Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEPHY34Cat.No.:HY-122650CASNo.:2130033-55-3分子式:C??H??O??分子量:582.55作用靶點:Autophagy作用通路:Autophagy儲存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性PHY34一種抑制ATP6V0A2和CAS進而抑制自噬(autophagy)的抑制劑，并具有納摩爾效應(yīng)。PHY34通過誘導(dǎo)凋亡(apoptosis)抑制癌細胞生長并抑制荷瘤模型中腫瘤生長。PHY34用于高級別漿液卵巢癌的研究。IC50&TargetATP6V0A2,cellularapoptosissusceptibility(CAS)[2]體外研究PHY34(0.001nM-50μM,72h)inhibitsvariouscancercellsgrowthwithnanomolarpotencythroughactivationofapoptosisbasedonenhancedcPARPlevelsandhasthehighestpotencyinHGSOCcelllines[1].PHY34(100nM,1μM;24h)blocksthefinalbreakdownoftheautolysosomesinOVCAR8at100nM,andinOVCAR3at1μM,respectively[1].PHY34(10nM,24h)inhibitsthelate-stageautophagythatprecedesapoptosisinductioninOVCAR8[1].PHY34(100nM,48h)inhibitsthelate-stageautophagythatprecedesapoptosisinductioninOVCAR3[1].PHY34(0.01nM-2μM,72h)inducescelldeathinthepresenceofwild-typeV0A2,butnotV823ImutantsinH4cell[2].PHY34(10,100nM;48h,72h)changessubcellularlocalizationofnuclearmultipleproteins[2].PHY34(20μM,1h)bindsspecificitywithATP6V0A2subunit[2].CellViabilityAssay[1][2]CellLine:OVCAR8,OVCAR3,HT-29,MDA-MB-435,MDA-MB-231,IOSE80,FT33Concentration:0.001nM-50μMIncubationTime:72h1/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEResult:InhibitedthegrowthofvariouscancercellswithIC50valuesof4nM(OVCAR8,OVCAR3),43.3nM(HT-29),23nM(MDA-MB-435),5.2nM(MDA-MB-231).ExhibitednotoxicitytoIOSE80andFT33(IC50>50μM).CellViabilityAssay[2]CellLine:H4Concentration:0.01nM-2μMIncubationTime:72hResult:InhibitedmutantcellwithanIC50valueof246pMthatwas1000-foldmorepotentthanHTP-013(434nM).ConferredresistanceinV8231mutationandnoimpactactivityinT216Amutation.ApoptosisAnalysis[1]CellLine:OVCAR8,OVCAR3Concentration:10nM,100nMIncubationTime:72hResult:IncreasedthenumberofcellsinearlyandlateapoptosisinOVCAR8andOVCAR3at10nMand100nM,respectively.CellAutophagyAssay[1]CellLine:HelaConcentration:9.31fM-20μMIncubationTime:4hResult:SustainedhighlevelsofLC3BpunctawithanEC50valueof2nM.InhibitedautophagywithanEC50valueof3.9nM.CellAutophagyAssay[2]CellLine:OVCAR3Concentration:5nMIncubationTime:4hResult:InhibitedautophagywithanED50valueof6.29nM,andwasmorepotentthanbafilomycinA1(HY-100558)withanED50valueof29.1nM.2/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEWesternBlotAnalysis[1][2]CellLine:OVCAR8,OVCAR3,OVCAR4Concentration:10nM,100nMIncubationTime:48h,72hResult:IncreasedcPARPlevelsinOVCAR8after48hat10nM,inOVCAR4andOVCAR3after72hat100nM,respectively.ReversedtheconversionofPARPtocPARPcombinedwithRAP(HY-10219)of1μM.WesternBlotAnalysis[2]CellLine:OVCAR8,OVCAR3,OVCAR4Concentration:10nMIncubationTime:24h,48h,72hResult:PromotedhistoneH3,LAMP1/2,ACSS2,andPCNAnuclearproteinaccumulationat48h.ReducedexpressionofKPNA2(Karyopherinsubunitalpha2)withtime-dependentmanner.Increasednuclearaccumulationofmutantp53at48h.體內(nèi)研究PHY34(0.75mg/kg,i.p.,3timesaweekfor3weeks)inhibitstumorgrowthandreducesKi67expressionintumortissueinafemalenudemousetumorbearingmodelconstructedbyOVCAR8[1].PHY34Pharmacokinetics[1]藥代動力學(xué)分析[1]ParameterUnitsIVIPPODosemg/kg0.61.875Dosenmol1029.93089.8128742.1T1/2hr6.28.412.3Tmaxhr0.080.250.25Cmaxnmol/L288.8519.5323.6AUClasthr*nmol/L198.8360.5599.9AUCinfhr*nmol/L215.8366.5663.3VzL/kg42.7101.63430.3CIL/hr/kg4.88.4194.1MRThrF*%-56.62.5AnimalModel:OVCAR8-inducedxenograftmodelsinfemalenudemice[1].Dosage:0.75mg/kg,threetimesaweekforthreeweeksAdministration:Intraperitonealinjection(i.p.)Result:Decreasedtumorburdenbasedonaverageabdominalradiantefficiencywithnogrosstoxicitythroughanalysisoffluorescenceimaging.3/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEREFERENCESYoungAN,etal.PhyllanthusminDerivativesInduceApoptosisandReduceTumorBurdeninHigh-GradeSerousOvarianCancerbyLate-StageAutophagyInhibition.MolCancerTher.2018Oct;17(10):2123-2135.SalviA,etal.PHY34inhibitsautophagythroughV-ATPaseV0A2subunitinhibitionandCAS/CSE1Lnuclearcargotraffickinginhighgradeserousovariancancer.CellDeathDis.2022