HDAC-IN-31-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEHDAC-IN-31Cat.No.:HY-144293CASNo.:1916505-13-9分⼦式:C₂₅H₂₄N₄O₂分⼦量:412.48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-31⼀种有效、选择性和具有⼝服活性的HDAC抑制剂，HDAC1、HDAC2、HDAC3、HDAC8的IC50值分别为84.90,168.0,442.7,>10000nM。HDAC-IN-31诱导细胞凋亡(apoptosis)和细胞周期停滞在在G2/M期。HDAC-IN-31显⽰出良好的抗肿瘤功效。HDAC-IN-31具有研究弥漫性⼤B细胞淋巴瘤的潜⼒[1]。IC50&TargetHDAC1HDAC2HDAC3HDAC884.90nM(IC50)168.0nM(IC50)442.7nM(IC50)>10000nM(IC50)体外研究HDAC-IN-31(compound24g)(2µM)showsgrowth-inhibitoryactivitieswiththeinhibitionrateof2.32%,44.01%,48.53%,64.94%forTMD-8,HCT116,A549,MDA-MB-231cells[1].HDAC-IN-31(1µM)showsselectivitywiththeIC50sof84.9,168.0,442.7,>10000nMforHDAC1,HDAC2,HDAC3,HDAC8,and81.20%,84.43%,88.07%,92.34%,96.88%,91.98%enzymeactivityforHDAC4,HDAC5,HDAC7,HDAC9,HDAC6,HDAC11,respectively[1].HDAC-IN-31(2.5,5,7.5,10µM;24h)increasestheexpressionofHDAC1,Ace-H3,Ace-H4,CleavedPARP,CleavedCaspase-3inadose-dependentmanner[1].HDAC-IN-31(0-4µM;24h)induceapoptosisandcellcyclearrestsinG2/Mphaseinadose-dependentmanner[1].CellProliferationAssay[1]CellLine:MDA-MB-231,A549,NCI-H460,HCT-116,SK-OV-3,HT-29,COLO678,NCI-H441,22Rv1,786-O,TMD-8,DOHH-2,CCRF-CEM,SU-DHL-2,REC-1,MOLT-4,HUT-78,RS4;11cells1/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEConcentration:0-20µMIncubationTime:72hResult:ShowedabroadspectrumofantitumoractivitywiththeIC50sof2.29,2.85,1.58,1.16,3.17,2.41,8.02,2.62,1.14,0.60,0.31,0.39,0.48,0.51,0.33,0.38,0.80,0.47µMforMDA-MB-231,A549,NCI-H460,HCT-116,SK-OV-3,HT-29,COLO678,NCI-H441,22Rv1,786-O,TMD-8,DOHH-2,CCRF-CEM,SU-DHL-2,REC-1,MOLT-4,HUT-78,RS4;11cells,respectively.WesternBlotAnalysis[1]CellLine:TMD-8cellsConcentration:2.5,5,7.5,10µMIncubationTime:24hResult:PromotedtheHDAC1,HDAC2,HDAC3substrateAce-H3andAce-H4acetylationwithadose-dependentmanner.ApoptosisAnalysis[1]CellLine:TMD-8cellsConcentration:0.5,1,2,4µMIncubationTime:24hResult:Inducedcellapoptosisataconcentration-dependentmanner.CellCycleAnalysis[1]CellLine:TMD-8cellsConcentration:250,500,1000nMIncubationTime:24hResult:ArrestedthecellcycleatG2/Mphaseinadose-dependentmanner.体内研究HDAC-IN-31(2mg/kgfori.v.;10,100mg/kgforp.o.)showsgoodbioavailabilitywithasignificantdosedependentmanner[1].HDAC-IN-31(50,100mg/kg;p.o,dailyfor21consecutivedays)showsgoodantitumorefficacyinaTMD-8xenograftmodelwithoutobvioustoxicity[1].PharmacokineticParametersofHDAC-IN-31inmice[1].ParametersUnit24g(25mg/kg)Cmaxng·h·mL-13100±231T1/2(po)h4.4±0.3AUC0-inf(iv)ng·h·mL-11040±1422/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAUC0-inf(po)ng·h·mL-15180±252MRTPOh2.6±0.4F%39.9±2.1ICRmouse;2mg/kgfori.v.;25mg/kgforp.o.[1].PharmacokineticParametersofHDAC-IN-31intumormodels[1].ParametersUnitpo(25mg/kg)po(50mg/kg)po(100mg/kg)Cmaxng·h·mL-11700±31714700±102410700±1001AUC0-tng·h·mL-11220±2429710±3149740±230AUC0-infng·h·mL-11230±1659730±3419770±332MRT0-th0.750±0.0430.812±0.0231.43±0.56MRT0-infh0.805±0.0860.821±0.0411.51±0.32Mouse;25,50,100mg/kgforp.o.[1].PharmacokineticParametersofHDAC-IN-31intumormodels[1].PKparametersUnitiv(2mg/kg)po(10mg/kg)po(100mg/kg)Cmaxng·h·mL-13960±41358300±1352T1/2h0.427±0.0161.31±0.271.63±0.52AUC0-infng·h·mL-11250±1322670±28657200±1047MRTh0.402±0.0320.919±0.0520.897±0.041CLmL·kg·min-127.2±1.2F%45.6±1.291.8±2.3ICRmice;2mg/kgfori.v.;10,100mg/kgforp.o.[1].PharmacokineticParametersofHDAC-IN-31intumormodels[1].PKparametersUnitMonkeyDogiv(1mg/kg)po(10mg/kg)iv(1mg/kg)po(10mg/kg)Cmaxng·h·mL-18520±3014740±243T1/2h4.31±0.569.14±0.321.65±0.411.51±0.33AUC0-infng·h·mL-115700±184253200±12412550±36515100±2004MRTh3.41±0.128.28±0.322.26±0.412.71±0.32CLmL·kg·min-11.35±0.216.72±0.35VdssL·kg-10.34±0.220.55±0.04F%27.6±2.158.9±1.2Dogsandmonkeys;1mg/kgfori.v.,10mg/kgforp.o.formonkey;1mg/kgfori.v.,10mg/kgforp.o.fordog[1].AnimalModel:ICRmice[1]Dosage:2mg/kgfori.v.;25mg/kgforp.o.(DMSO/PEG200/saline=20:20:60,v/v/v)Administration:I.v.orp.o.Result:Showedhighoralbioavailability(F=40%).AnimalModel:Mouse[1]Dosage:25,50,100mg/kgAdministration:P.o.Result:Didnotexhibitasignificantdosedependentfororaladministration.AnimalModel:ICRmice[1]Dosage:2,10,100mg/kg(intotheformofhydrochloride)Administration:2mg/kgfori.v.;10,100mg/kgforp.o.Result:Showedgoodbioavailabilitywithasignificantdosedependent.AnimalModel:Dogsandmonkeys[1]3/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEDosage:1,10mg/kgAdministration:1mg/kgfori.v.;10mg/kgforp.o.Result:Showedgoodpharmacokineticcharacteristicsfordifferentspecies.AnimalModel:5-6weeks,femaleCB.17SCIDmice(TMD-8tumorxenografts)[1]Dosage:50,100mg/kgAdministration:P.o,dailyfor21consecutivedaysResult:Inhibitedthetumorgrowthwiththeinhibitionrateof77%andhadnosignificanteffectontheinternalorgansofmiceat100mg/kg/d.REFERENCES[1].CuiH,etal.DesignandsynthesisofHDACinhibitorstoenhancethetherapeuticeffectofdiffuselargeB-celllymphomabyimprovingmetabolicstabilityand