HDAC-IN-57-DataSheet-生命科學(xué)試劑-MCE

Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEHDAC-IN-57Cat.No.:HY-149946CASNo.:2716217-79-5分子式:C??H??N?O?分子量:377.39作用靶點(diǎn):HDAC;Apoptosis;HistoneDemethylase作用通路:CellCycle/DNADamage;Epigenetics;Apoptosis儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性HDAC-IN-57是一種具有口服活性的組蛋白脫乙酰酶(HDAC)泛抑制劑，對(duì)HDAC1,HDAC2,HDAC6,HDAC8的IC50值分別為2.07nM,4.71nM,2.4nM和107nM。HDAC-IN-57可抑制LSD1，對(duì)LSD1的IC50值為1.34μΜ。HDAC-IN-57誘導(dǎo)凋亡(apoptosis)，具有抗腫瘤活性[1]。IC50&TargetHDAC1HDAC2HDAC6HDAC82.07nM(IC50)4.71nM(IC50)2.4nM(IC50)107nM(IC50)體外研究HDAC-IN-57(Compound5e)(1.0μM,2.5μM,5.0μΜ；48hour)inhibitsmigrationandinvasionactivityofMGC-803andHCT-116cells[1].HDAC-IN-57(1.0μM,2.5μM,5.0μΜ；48hour)significantlyinhibitsthegrowthofsolidtumorcelllinesMGC-803,A549,andHCT-116,withIC50sof0.45μM.1.48μMand0.57μM,respectively[1].HDAC-IN-57(1.0μM.2.5μM,5.0μΜ;48hours)triggersapoptosisofMGC-803andHCT-116cellsinadose-dependentmanner[1].HDAC-IN-57(1.0μM.2.5μM,5.0μΜ;48hours)inhibitsLSD1andHDACsofMGC-803andHCT-116cells[1].HDAC-IN-57(1.0μM.2.5μM,5.0μΜ;48hours)inducesG2/McyclearrestinMGC-803andHCT-116cells[1].HDAC-IN-57(Compound5e)showesexcellentmetabolicstabilityinhumanliver(HLM)andratlivermicrosomes(RLM),maintaining86.1%and87.4%,respectively,oftheparentcompoundafterincubationfor1h,withT1/2valuesover120min[1].WesternBlotAnalysis[1]1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemECellLine:MGC-803cells,HCT-116cellsConcentration:1.5μMIncubationTime:48hoursResult:InhibitedcellularLSD1andHDACs.Upregulatedtheexpressionofapoptoticmarkers,includingcytochromeC,Bax,cleavedcaspase-3/7/9,andcleavedPARP,whiledownregulatingtheexpressionofanti-apoptoticproteinBcl-2.ApoptosisAnalysis[1]CellLine:MGC-803cells,HCT-116cellsConcentration:1.0μM,2.5μM,5.0μMIncubationTime:48hoursResult:TriggeredMGC-803andHCT116cellsapoptosisinadose-dependentmanner.Inducedabout55.4%and51.5%MGC-803cellapoptosisataconcentrationof5μM.CellMigrationAssay[1]CellLine:MGC-803cells,HCT-116cellsConcentration:1.0μM,2.0μM,4μMIncubationTime:48hoursResult:ReducedthenumberofmigratedofMGC-803andHCT-116cells.Inhibitedthemigrationandinvasionofcancercells.CellCycleAnalysis[1]CellLine:MGC-803cells,HCT-116cellsConcentration:1.0μM,2.5μM,5.0μMIncubationTime:48hoursResult:InducedG2/McyclearrestinMGC-803andHCT-116cells.體內(nèi)研究HDAC-IN-57(Compound5e)(1mg.kgfori.v.,10mg/kgforp.o.)showsaT1/2of0.37h(i.v.)and2.75h(p.o.),andoralbioavailability(F%)of10.6%[1].HDAC-IN-57(25or50mg/kg,oralgavageoncedailyfor21consecutivedays)achievesadose-dependentinhibitionfortumorgrowthinanMGC-803xenograftmodelwithNOD-SCIDmice[1]..2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEAnimalModel:MGC-803xenograftmodelinNOD-SCIDmice[1]Dosage:25or50mg/kgAdministration:Oralgavage(p.o.);Result:Achievedadose-dependenttumorgrowthinhibition(TGI)of44.8%at25mg/kgand71.5%at50mg/kg.AnimalModel:MaleSDrats(Pharmacokineticassay)[1]Dosage:1mg/kg;10mg/kgAdministration:Intravenousinjection(i.v.);Oralgavage(p.o.)Result:PharmacokineticparametersforHDAC-IN-57(Compound5e)inSDrats[1]RouteDose(mg/kg)T1/2(h)Tmax(h)CL(mL?min-1/kg-1)AUC0-t(h?ng/mL)AUC0-(h?ng/mL)Cmax(ng/mL)VZ(L/kg)F(%)i.v.10.37/1.61644.1645.81892.80.82/p.o.102.750.25/685.2766.2716.452.210.6REFERENCESDuanY,etal.Discoveryofnovel,potent,andorallybioavailableHDACsinhibitorswithLSD1inhibitoryactivityforthetreatmentofsolidtumors.EurJMedChem.2023Jun5;254:115367.McePdfHeightCautio