HDAC1-IN-3-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEHDAC1-IN-3Cat.No.:HY-144297分⼦式:C₂₂H₂₄ClN₇O₂分⼦量:453.92作⽤靶点:HDAC作⽤通路:CellCycle/DNADamage;Epigenetics储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性HDAC1-IN-3⼀种有效的PfHDAC1抑制剂。HDAC1-IN-3在野⽣型和耐多药寄⽣⾍株中均显⽰出抗疟活性。HDAC1-IN-3对寄⽣⾍所有⽣命周期显⽰出显著的体内杀伤作⽤[1]。IC50&TargetHDAC1HDAC2HDAC3HDAC62.2nM(IC50)5.1nM(IC50)5.2nM(IC50)85.5nM(IC50)HDAC829.9nM(IC50)体外研究HDAC1-IN-3(compoundJX35)showsantimalarialactivitywithIC50sof1.26nMand1.61nMforwild-typePlasmodiumfalciparum(P.falciparum)parasite3D7andchloroquine-resistantP.falciparumparasiteDd2,respectively[1].HDAC1-IN-3(10µM;72h)showslowcytotoxicitywithIC50sof1.02µMand1.21µMforHepG2,293Tcells,respectively[1].HDAC1-IN-3(72h)showsnocross-resistancewithclinicalantimalarialdrugswithIC50sof3.06,2.18,5.85nMforGB4,C2A,CP286,respectively[1].HDAC1-IN-3(10,30,60,100nM;3,6,12,24h)showsantimalarialactivityinatime-anddose-dependentmannerwithasynchronous3D7parasites[1].HDAC1-IN-3(40nM,4days;P.falciparum3D7cells)showsthekillingeffectsofJX35onP.falciparumparasitesduringasexualreproductionstagesmightberelatedtotheinhibitionofschizontgrowthandreinvasionofRBCs(redbloodcells)[1].HDAC1-IN-3(5,20nM;4h)inhibitstheexpressionofPfHDACagainstART(artemisinin)-resistantparasitestrains[1].HDAC1-IN-3reducestheinhibitionofhHDACswithIC50sof2.2,5.1,5.2,85.5,29.9nMforHDAC1,HDAC2,1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEHDAC3,HDAC6,HDAC8,respectively[1].CellCytotoxicityAssay[1]CellLine:HepG2,293TcellsConcentration:10µMIncubationTime:72hResult:ShowedlowcytotoxicitywithIC50sof1.02µMand1.21µMforHepG2,293Tcells,respectively.WesternBlotAnalysis[1]CellLine:P.falciparum3D7cellsConcentration:5,20nMIncubationTime:4hResult:InhibitedtheexpressionofPfHDACagainstART(artemisinin)-resistantparasitestrains.体内研究HDAC1-IN-3(30,60,90mg/kg;i.p.;oncedailyfor5days)showsacceptabletherapeuticefficacyandsafety[1].HDAC1-IN-3(5mg/kg;i.p.)showsgoodpharmacokineticproperties[1].PharmacokineticParametersofHDAC1-IN-3inFemaleBALB/cmice[1].parameterJX35Cmax(ng/mL)539Tmax(h)0.25AUClast(h·ng/mL)638AUCinf(h·ng/mL)640t1/2(h)0.91CLZ/F(L/h/kg)7.81VZ/F(L/kg)10.20FemaleBALB/cmice;5mg/kg;i.p.AnimalModel:6-8weeks,BALB/cfemalemice[1]Dosage:30,60,90mg/kgAdministration:I.p.,oncedailyfor5daysResult:Showedacceptabletherapeuticefficacyandsafety.AnimalModel:6-8weeks,femaleBALB/cmice[1]Dosage:5mg/kgAdministration:I.p.Result:Showedgoodpharmacokineticproperties.REFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].WangM,etal.DrugRepurposingofQuisinostattoDiscoverNovelPlasmodiumfalciparumHDAC1InhibitorswithEnhancedTriple-StageAntimalarialActivityandImprovedSafety.JMedChem.2022;65(5):4156-4181.McePdfHeightCaution:Producthasnotbeenfullyvalidat