Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEHDAC-IN-50Cat.No.:HY-152146CASNo.:2653339-26-3分?式:C??H??N?O?分?量:575.7作?靶點(diǎn):Apoptosis;FGFR;HDAC作?通路:Apoptosis;ProteinTyrosineKinase/RTK;CellCycle/DNADamage;Epigenetics儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性HDAC-IN-50?種有效的，具有?服活性的FGFR和HDAC雙重抑制劑，對(duì)FGFR1,FGFR2,FGFR3,FGFR4,HDAC1,HDAC2,HDAC6,HDAC8的IC50值分別為0.18,1.2,0.46,1.4,1.3,1.6,2.6,13nM。HDAC-IN-50誘導(dǎo)細(xì)胞凋亡(Apoptosis)和細(xì)胞周期停滯在G0/G1期。HDAC-IN-50降低pFGFR1、pERK、pSTAT3的表達(dá)。HDAC-IN-50具有抗腫瘤活性[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)體外研究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?邊的抑制劑?師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.體內(nèi)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?邊的抑制劑?師www.MedChemEResult:InhibitedthetumorgrowthanddownregulatedtheexpressionofpSTAT3,pFGFR1,increasedtheexpressionofAc-H3.REFERENCES[1].WanG,etal.DesignandSynthesisofFibroblastGrowthFactorReceptor(FGFR)andHistoneDeacetylase(HDAC)DualInhibitorsfortheTreatmentofCancer.JMedChem.2022Dec22;65(24):16541-16569.McePdfHeightCaution:Producthasnotbeenfullyval