Wee1-HDAC-IN-1-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEWee1/HDAC-IN-1Cat.No.:HY-179272CASNo.:3037071-29-4分⼦式:C₃₃H₄₃N₉O₄分⼦量:629.75作⽤靶点:Wee1;HDAC;Apoptosis作⽤通路:CellCycle/DNADamage;Epigenetics;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Wee1/HDAC-IN-1⼀种双Wee1/HDAC抑制剂，对Wee1、HDAC1、HDAC3和HDAC6的IC50值分别为1.2nM、196nM、156nM和55nM。Wee1/HDAC-IN-1对MV4-11细胞表现出强的抗增殖活性，其IC50值为0.076μM。Wee1/HDAC-IN-1选择性地结合到Wee1和HDACs的催化位点，⼲扰DNA损伤修复通路，并诱导MV4-11细胞凋亡(apoptosis)。Wee1/HDAC-IN-1可⽤于急性髓系⽩⾎病的研究[1]。IC50&TargetWee1HDAC1HDAC3HDAC61.2nM(IC50)196nM(IC50)156nM(IC50)55nM(IC50)HDAC2HDAC8HDAC10HDAC11>2000nM(IC50)1295nM(IC50)1310nM(IC50)>2000nM(IC50)体外研究Wee1/HDAC-IN-1(Compound23f)(72h)exhibitsstrongantiproliferativeactivityindifferentAMLcelltypes.Wee1/HDAC-IN-1againstMV4-11cells,THP-1cellsandHL-60cellswithIC50valuesof0.076μM,0.773μMand0.309μM,respectively[1].Wee1/HDAC-IN-1(10-75nM;96h)hasdifferentiation-inducingabilityinMV4-11cells[1].Wee1/HDAC-IN-1(37.5-600nM;72h)inducescellapoptosisinadose-dependentmannerinMV4-11cells[1].Wee1/HDAC-IN-1(19-1200nM;72h)dose-dependentlyreducedthephosphorylationlevelofCDK1whileincreasingtheexpressionofacetylatedhistoneH3.Wee1/HDAC-IN-1coulddose-dependentlypromotetheexpressionofγH2A.X,abiomarkerforDNAdouble-stranddamage[1].ApoptosisAnalysis[1]1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:MV4-11Concentration:37.5,75,150,300,600nMIncubationTime:72hResult:Inducedcellapoptosisinadose-dependentmanner,withanotableincreaseinapoptosis(56.90%)observedataconcentrationof600nM.WesternBlotAnalysis[1]CellLine:MV4-11Concentration:19,75,300,1200nMIncubationTime:72hResult:ReducedthephosphorylationlevelofCDK1,increasedtheexpressionofacetylatedhistoneH3,andpromotedtheexpressionofyH2A.X.CellDifferentiationAssay[1]CellLine:MV4-11cellsConcentration:10,25,50,75nMIncubationTime:96hResult:InducedanincreaseinCD11bexpression,indicatingacertaindifferentiation-inducingability.体内研究Wee1/HDAC-IN-1(Compound23f)(15-60mg/kg;Intraperitoneal;oncedaily;21days)inhibitstumorgrowthinsubcutaneousinjectionofMV4-11cellsinBALB/cnude[1].Wee1/HDAC-IN-1(120-150mg/kg;i.v;once)showsacceptablehepaticandrenalsafetyprofilesinICRmice(18-20g)[1].AnimalModel:BALB/cnude(female,6-8weeksold)weresubcutaneousinjectionofMV4-11cells,1×107cells/mouse[1]Dosage:15mg/kg,30mg/kg,60mg/kgAdministration:Intraperitoneal;oncedaily;21daysResult:Tumorgrowthwassignificantlyinhibitedinadose-dependentmanner.Mediansurvivaltimewasincreased.Inducedsignificantmorphologicalchangesintumorcells,includingcellshrinkage,aggregation,andchromatinmarginalization.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE\r\nReducedthecompensatoryCHK1activationcausedbyWee1inhibition.AnimalModel:ICRmice(18-20g)[1]Dosage:120mg/kg,150mg/kgAdministration:Tailveininjection;onceResult:Nosignificantchangesinbiochemicalparameters(ALT、ASTandBUN)ormorphologicalchangesinmajororganswereobserved,indicatingacceptablehepaticandrenalsafetyprofilesandlowpotentialtoxicity.REFERENCES[1].ZhangW,etal.DiscoveryofNovelandHighlyPotentWee1andHDACDual-TargetInhibitorsfortheTreatmentofAcuteMyeloidLeukemia.JMedChem.2025;68(21):22845-22873.McePdfHeightCaution:Producth