3-Deazaneplanocin-A-DZNep-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemE3-DeazaneplanocinACat.No.:HY-10442CASNo.:102052-95-9Synonyms:DZNep;3-Deazaneplanocin分⼦式:C₁₂H₁₄N₄O₃分⼦量:262.26作⽤靶点:HistoneMethyltransferase;Orthopoxvirus作⽤通路:Epigenetics;Anti-infection储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1monthBIOLOGICALACTIVITY⽣物活性3-DeazaneplanocinA(DZNep)⼀种有效的组蛋⽩甲转移酶(histonemethyltransferase，EZH2)抑制剂。3-DeazaneplanocinA⼀种有效的S-腺苷同型半胱氨酸⽔解酶(AHCY)抑制剂。3-DeazaneplanocinA具有抗正痘活性。IC50&TargetEZH2[1]体外研究3-DeazaneplanocinAisapotenthistonemethyltransferaseEZH2inhibitor.TreatmentofOCI-AML3cellswith3-DeazaneplanocinA(1.0μM)resultsinasignificantincreaseinaccumulationofcellsintheG0/G1phase(58.5%)withaconcomitantdecreaseinthenumberofcellsinSphase(35.2%)andG2/Mphases(6.3%)ofthecellcycle(P[1].3-DeazaneplanocinAreducestheexpressionofEZH2,especiallyafter72hours(e.g.48%,32%and36%reductionofEZH2inPANC-1,MIA-PaCa-2andLPc006cells,respectively)[2].3-DeazaneplanocinAshowsminimalgrowthinhibitioninPANC-1cells.Morethan50%ofthesecellsarestillgrowingafterexposureatthehighestconcentration(20μM).MIA-PaCa-2andLPc006cellsaremuchmoresensitive,withIC0valuesof1±0.3and0.1±0.03μM,respectively[2].3-DeazaneplanocinAcausesdose-dependentinhibitionofcellproliferationofNSCLCcelllines,andtheIC0valuesrangefrom0.08to0.24μM[3].体内研究ThesurvivalofNOD/SCIDmicewithacutemyeloidleukemia(AML)duetoHL-60cellsissignificantlyhigher,iftreatedwith3-DeazaneplanocinAandPanobinostat(PS)comparetotreatmentwithPS,3-1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEDeazaneplanocinA,orvehiclealone(P[1].Thereisaprogressiveincreaseinweightofratstreatedwithphysiologicalsalineinatime-dependentmanner(themeangrowthrate=3.19%perday).Administrationof20mg/kg3-DeazaneplanocinAnotonlymarkedlyreducestherelativeweightoftheratscomparetotheinitialweight(−2.0%,−4.9%and−1.2%)inthefirstthreedayspost-treatment,butalsosuppressestheweightgrowthrateto2.6%perdayfromthefourthdayonwardspost-dose[4].PROTOCOLCellAssay[1]AMLHL-60cellsareobtainedandmaintained.OCI-AML-3cellsareculturedinαminimumessentialmediumwith10%fetalbovineserum,1%penicillin/streptomycin,and1%nonessentialaminoacids.Toanalyzesynergismbetween3-DeazaneplanocinAandPSininducingapoptosis,cellsaretreatedwith3-DeazaneplanocinA(100-750nM)andPS(5-20nM)ataconstantratiofor48hours.Thepercentageofapoptoticcellsisdeterminedbyflowcytometry.Thecombinationindex(CI)foreachdrugcombinationisobtainedbymediandoseeffectofChouandTalalay,usingtheCIequationwithinthecommerciallyavailablesoftwareCalcusyn[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1][4]HL-60cells(5million)areinjectedintothetailveinoffemalenonobesediabetic/severecombinedimmunodeficiency(NOD/SCID)mice,andthemicearemonitoredfor7days.Thefollowingtreatmentsareadministeredincohortsof7miceforeachtreatment:vehiclealone,1mg/kg3-DeazaneplanocinA,10mg/kgPS,and3-DeazaneplanocinAplusPS.Treatmentsareinitiatedonday7.3-DeazaneplanocinAisadministeredtwiceperweek(Tuesday-Thursday)intraperitoneallyfor2weeks,andthendiscontinued.PSisadministered3daysperweek(Monday,Wednesday,andFriday)for4weeks.ThesurvivalofmicefromthetailveinmodelisrepresentedwithaKaplan-Meiersurvivalplot.Rats[4]Malewistarratsareused.TheacutetoxicitystudyiscarriedouttodeterminetheNOAELof3-DeazaneplanocinAinrats.Intotal,20ratsaredividedinto4groupsoffiveeach.Threegroupsareintravenouslyadministered20,15,10mg/kgbodyweight(BW)3-DeazaneplanocinAsolutionbythetailvein.Theremaininggroupisgivenphysiologicalsaline(0.9%NaClsaline)asthecontrolgroup.Then,theNOAELoffree3-DeazaneplanocinAisdetermined,dependingonthefollowingendpointparametersobtained.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•NatCommun.2022Jan10;13(1):12.•NatCommun.2021Feb23;12(1):1237.•JImmunotherCancer.2019Nov14;7(1):300.•JAmSocNephrol.2016Jul;27(7):2021-34.•CellDeathDis.2020Oct23;11(10):906.Seemorecustomervalidationsonwww.MedChemE2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEREFERENCES[1].SmeeDF,etal.Areviewofcompoundsexhibitinganti-orthopoxvirusactivityinanimalmodels.AntiviralRes.2003Jan;57(1-2):41-52.[2].FiskusW,etal.CombinedepigenetictherapywiththehistonemethyltransferaseEZH2inhibitor3-deazaneplanocinAandthehistonedeacetylaseinhibitorpanobinostatagainsthumanAMLcells.Blood,2009,114(13),2733-2743.[3].AvanA,etal.MolecularmechanismsinvolvedinthesynergisticinteractionoftheEZH2inhibitor3-deazaneplanocinAwithgemcitabineinpancreaticcancercells.MolCancerTher.2012Aug;11(8):1735-46.[4].KikuchiJ,etal.Epigenetictherapywith3-deazaneplanocinA,aninhibitorofthehistonemethyltransferaseEZH2,inhibitsgrowthofnon-smallcelllungcancercells.LungCancer.2012Nov;78(2):138-43.[5].SunF,etal.Preclinicalpharmacokineticstudiesof3-deazaneplanocinA,apotentepigeneticanticanceragent,anditshumanpharmacokineticpredictionusingGastroPlus?.Eu