HDAC-IN-73-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemEHDAC-IN-73Cat.No.:HY-161688CASNo.:2323571-16-8分子式:C₂₂H₂₄Br₂N₄O₆Se₂分子量:758.18作用靶点:Apoptosis;HDAC作用通路:Apoptosis;CellCycle/DNADamage;Epigenetics储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性HDAC-IN-73(compoundP-503)是一种组蛋白脱乙酰酶(HDAC)抑制剂，与PsA(HY-N2150)相比，对HDAC1的抑制活性较差，对HDAC6的抑制活性相同或略高。HDAC-IN-73对HDAC1和HDAC6的IC50s值分别为0.17、0.49µM。值得注意的是，HDAC-IN-73对HDAC6的抑制效力增强，其疗效是PsA的9倍(IC50=3.9µM)。HDAC-IN-73具有有效的抗增殖活性，诱导细胞凋亡，并导致细胞在G2/M期停滞。HDAC-IN-73具有用于结肠癌等癌症研究的潜力[1]。IC50&TargetHDAC1HDAC60.17μM(IC50)0.49μM(IC50)体外研究HDAC-IN-73(compoundP-503)(0-10µM;48h)caninhibitproliferationofHCT116cellswithIC50valueof0.24µMwhilePsA’sIC50valueis3.05µM[1].HDAC-IN-73(0.25-2µM;24h)canincreasetheacetylationlevelsofhistoneH3orα-tubulininHCT116cellscomparingwithPsA[1].HDAC-IN-73(0.1-0.2µM;24h)caninduceapoptosisofHCT116cellsandhasasuperiorproapoptoticeffecttoPsA[1].HDAC-IN-73(0.2-0.4µM;48h)caninduceHCT116cellcyclearrestatG2/MphasewhilePsAincreasesproportionofG1phase[1].CellProliferationAssay[1]CellLine:HCT116cellsConcentration:0-10µMIncubationTime:48hoursResult:ShowedantiproliferativeactivitywithIC50valueof0.24µM.1/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEApoptosisAnalysis[1]CellLine:HCT116cellsConcentration:0.2,0.4µMIncubationTime:48hoursResult:Inducedapoptosiswith71.94%ofapoptoticcells(bothearlyandlateapoptoticcells)atdefineconcentrationof0.4μM,comparedwithPsA(56.5%,4μM).CellCycleAnalysis[1]CellLine:HCT116cellsConcentration:0.1,0.2µMIncubationTime:24hoursResult:InducedcellcyclearrestatG2/MphasewhilePsAincreasedproportionofG1phase.HDAC-IN-73with0.1μMand0.2μMcanleadto47.92%and74.56%ofthecellsinG2/Mphase,respectively.WesternBlotAnalysis[1]CellLine:HCT116cellsConcentration:0.25,0.5,1,2µMIncubationTime:24hoursResult:IncreasedtheacetylationlevelsofhistoneH3orα-tubulininadosedependentmannercomparingwithPsA.体内研究HDAC-IN-73(compoundP-503)(5mg/kg;i.p.;every2daysfor26days)demonstratesanotableantitumoractivitybutalsoexistshighertoxicityinHCT116xenograftmodel[1].AnimalModel:6weeks,Femalenudemice(BALB/c-nu)(HCT116xenograftmodel)[1]Dosage:5mg/kgAdministration:I.p.;every2daysfor26daysResult:Reducedthetumorvolume(p<0.0001)andthetumorweight(p<0.01).Exhibitedthesignificantlossofbodyweightwhichhasthesametrendwiththegroupofnegativecontrol.Inhibitedthetumorgrowth(TGI=74.6%),whiletheTGIofSAHA(10mg/kg,positivecontrol)andPsA(10mg/kg)were13.1%and36.1%,respectively.Existedhightoxicity,2micediedduringthemedication.WesternblottestsshowedthatAc-H3and2/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEAc-α-tubulinintumortissueswereup-regulated.REFERENCESJiangY,etal.PsammaplinAanalogueswithmodifieddisulfidebondtargetinghistonedeacetylases:Synthesisandbiologicalevaluation.EurJMedChem.2024May31;275:116541.McePdfHeightCaution:Producthasnotbeenfullyv