HDAC-IN-50-DataSheet-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEHDAC-IN-50Cat.No.:HY-152146CASNo.:2653339-26-3分⼦式:C₃₁H₄₁N₇O₄分⼦量:575.7作⽤靶点:Apoptosis;FGFR;HDAC作⽤通路:Apoptosis;ProteinTyrosineKinase/RTK;CellCycle/DNADamage;Epigenetics储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性HDAC-IN-50⼀种有效的，具有⼝服活性的FGFR和HDAC双重抑制剂，对FGFR1,FGFR2,FGFR3,FGFR4,HDAC1,HDAC2,HDAC6,HDAC8的IC50值分别为0.18,1.2,0.46,1.4,1.3,1.6,2.6,13nM。HDAC-IN-50诱导细胞凋亡(Apoptosis)和细胞周期停滞在G0/G1期。HDAC-IN-50降低pFGFR1、pERK、pSTAT3的表达。HDAC-IN-50具有抗肿瘤活性[1]。IC50&TargetFGFR1FGFR2FGFR3FGFR40.18nM(IC50)1.2nM(IC50)0.46nM(IC50)1.4nM(IC50)HDAC1HDAC2HDAC6HDAC81.3nM(IC50)1.6nM(IC50)2.6nM(IC50)13nM(IC50)体外研究HDAC-IN-50(compound10e)(0.1,1,10,100nM;12-84h)inducesapoptosisandcellcyclearrestatG0/G1phaseinatimeanddose-dependentmanner[1].HDAC-IN-50(0,1.25,2.5,5µMforHCT116cells,0,1,10,100nMforSNU-16cells;36h)decreasestheexpressionofpFGFR1,pERK,pSTAT3inadose-dependentmanner[1].CellProliferationAssay[1]CellLine:HCT116,SNU-16,KATOIII,A2780,K562,JurkatcellsConcentration:0-30µMIncubationTime:72h1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:ShowedantiproliferativeactivitieswithIC50sof0.82,0.0007,0.0008,0.04,2.46,15.14µMforHCT116,SNU-16,KATOIII,A2780,K562,Jurkatcells,respectively.CellCycleAnalysis[1]CellLine:SNU-16cellsConcentration:0.1,1,10,100nMIncubationTime:12,24,36hResult:InducedcellcyclearrestatG0/G1phaseinatimeanddose-dependentmanner.ApoptosisAnalysis[1]CellLine:SNU-16cellsConcentration:0.1,1,10,100nMIncubationTime:36,48,60,72,84hResult:Inducedapoptosiswiththeapoptoticrateincreased30.8%and49.6%at10,100nM,respectively.WesternBlotAnalysis[1]CellLine:HCT116,SNU-16cellsConcentration:0,1.25,2.5,5µMforHCT116cells,0,1,10,100nMforSNU-16cellsIncubationTime:36hResult:ReducedtheexpressionofpFGFR1,pERK,pSTAT3inadose-dependentmanner.体内研究HDAC-IN-50(15,30mg/kg;p.o.;dailyfor18days)showsanti-tumoractivityinmouse[1].PharmacokineticParametersofHDAC-IN-50infemaleSprague–Dawley(SD)rats[1].dose(mg/kg)administrationrouteT1/2(h)Tmax(h)Cmax(ng/mL)AUC0-∞(h·ng/mL)CL(mL/min/kg)Vss(mL/kg)F%2IV0.98±0.120.081116.63±320.45424.88±89.5680.64±15.592788.87±765.115IP1.83±0.062101.57±23.05491.25±84.1843.8330PO0.77±0.044442.53±46.331557.12±355.6124.83FemaleSprague-Dawley(SD)rats,5mg/kgiv;5mg/kgip;30mg/kgp.o.[1]AnimalModel:BALB/cnudemice(HCT116xenograftmodel)[1]Dosage:15,30mg/kgAdministration:P.o.;dailyfor18days2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:InhibitedthetumorgrowthanddownregulatedtheexpressionofpSTAT3,pFGFR1,increasedtheexpressionofAc-H3.REFERENCES[1].WanG,etal.DesignandSynthesisofFibroblastGrowthFactorReceptor(FGFR)andHistoneDeacetylase(HDAC)DualInhibitorsfortheTreatmentofCancer.JMedChem.2022Dec22;65(24):16541-16569.McePdfHeightCaution:Producthasnotbeenfullyval