Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemE3-DeazaneplanocinACat.No.:HY-10442CASNo.:102052-95-9Synonyms:DZNep;3-Deazaneplanocin分?式:C??H??N?O?分?量:262.26作?靶點(diǎn):HistoneMethyltransferase;Orthopoxvirus作?通路:Epigenetics;Anti-infection儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1monthBIOLOGICALACTIVITY?物活性3-DeazaneplanocinA(DZNep)?種有效的組蛋?甲轉(zhuǎn)移酶(histonemethyltransferase，EZH2)抑制劑。3-DeazaneplanocinA?種有效的S-腺苷同型半胱氨酸?解酶(AHCY)抑制劑。3-DeazaneplanocinA具有抗正痘活性。IC50&TargetEZH2[1]體外研究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].體內(nèi)研究ThesurvivalofNOD/SCIDmicewithacutemyeloidleukemia(AML)duetoHL-60cellsissignificantlyhigher,iftreatedwith3-DeazaneplanocinAandPanobinostat(PS)comparetotreatmentwithPS,3-1/3MasterofBioactiveMolecules—您?邊的抑制劑?師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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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?邊的抑制劑?師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