Azacitidineisapyrimidinenucleosideanalogueofcytidinewithantineoplasticactivity.AzacitidineisincorporatedintoDNA,whereitreversiblyinhibitsDNAmethyltransferase,therebyblockingDNAmethylation.HypomethylationofDNAbyazacitidinemayactivatetumorsuppressorgenessilencedbyhypermethylation,resultinginanantitumoreffect.ThisagentisalsoincorporatedintoRNA,therebydisruptingnormalRNAfunctionandimpairingtRNAcytosine-5-methyltransferaseactivity.

MedKooCat#:100070
Name:Azacitidine
CAS#:320-67-2
ChemicalFormula:C8H12N4O5
ExactMass:244.08077
MolecularWeight:244.2
ElementalAnalysis:C,39.35;H,4.95;N,22.94;O,32.76


Synonym:U18496;U-18496;U18496;Abbreviations:5AC;5AZC.5-azacytidine;azacytidine;ladakamycin.USbrandnames:Mylosar;Vidaza.

IUPAC/ChemicalName:4-amino-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-1,3,5-triazin-2(1H)-one

InChiKey:NMUSYJAQQFHJEW-KVTDHHQDSA-N

InChiCode:InChI=1S/C8H12N4O5/c9-7-10-2-12(8(16)11-7)6-5(15)4(14)3(1-13)17-6/h2-6,13-15H,1H2,(H2,9,11,16)/t3-,4-,5-,6-/m1/s1

SMILESCode:O=C1N([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)C=NC(N)=N1


TechnicalData

Appearance:
whitesolidpowder

Purity:
>98%(orrefertotheCertificateofAnalysis)

CertificateofAnalysis:
ViewCoA:currentbatch,Lot#YYP30917

QCData:
ViewQCdata:currentbatch,Lot#YYP30917

SafetyDataSheet(MSDS):
ViewMaterialSafetyDataSheet(MSDS)

ShippingCondition:
Shippedunderambienttemperatureasnon-hazardouschemical.ThisproductisstableenoughforafewweeksduringordinaryshippingandtimespentinCustoms.

StorageCondition:
Dry,darkandat0-4Cforshortterm(daystoweeks)or-20Cforlongterm(monthstoyears).

Solubility:
SolubleinDMSO,notinwater

ShelfLife:
>10yearsifstoredproperly

DrugFormulation:
ThisdrugmaybeformulatedinDMSO

StockSolutionStorage:
0-4Cforshortterm(daystoweeks),or-20Cforlongterm(months).

HarmonizedSystemCode:
293490


AdditionalInformation

Accordingtohttp://en.wikipedia.org/wiki/Azacitidine,Azacitidineismainlyusedinthetreatmentofmyelodysplasticsyndrome(MDS),forwhichitreceivedapprovalbytheU.S.FoodandDrugAdministrationonMay19,2004;itismarketedasVidaza.InarandomizedcontrolledtrialcomparingazacitidinetosupportivetreatmentofMDS,around16%ofpeoplereceivingthedrughadacompleteorpartialresponse—bloodcellcountsandbonemarrowmorphologyreturningtonormal—and2/3patientswhorequiredbloodtransfusionsbeforethestudynolongerneededthemafterreceivingazacitidine.ItcanalsobeusedinvitrotoremovemethylgroupsfromDNA.Thismayweakentheeffectsofgenesilencingmechanismsthatoccurredpriortothemethylation.MethylationeventsarethereforebelievedtosecuretheDNAinasilencedstate.Demethylationmayreducethestabilityofsilencingsignalsandthusconferrelativegeneactivation.
   
DRUGDESCRIPTION
VIDAZA(azacitidineforinjection)containsazacitidine,whichisapyrimidinenucleosideanalogofcytidine.Azacitidineis4-amino-1-β-D-ribofuranosyl-s-triazin-2(1H)-one. TheempiricalformulaisC8H12N4O5.Themolecularweightis244.Azacitidineisawhitetooff-whitesolid.Azacitidinewasfoundtobeinsolubleinacetone,ethanol,andmethylethylketone;slightlysolubleinethanol/water(50/50),propyleneglycol,andpolyethyleneglycol;sparinglysolubleinwater,watersaturatedoctanol,5%dextroseinwater,N-methyl-2-pyrrolidone,normalsalineand5%Tween80inwater;andsolubleindimethylsulfoxide(DMSO).Thefinishedproductissuppliedinasterileformforreconstitutionasasuspensionforsubcutaneousinjectionorreconstitutionasasolutionwithfurtherdilutionforintravenousinfusion.VialsofVIDAZAcontain100mgofazacitidineand100mgmannitolasasterilelyophilizedpowder.
 
MechanismofAction
VIDAZAisapyrimidinenucleosideanalogofcytidine.VIDAZAisbelievedtoexertitsantineoplasticeffectsbycausinghypomethylationofDNAanddirectcytotoxicityonabnormalhematopoieticcellsinthebonemarrow.TheconcentrationofazacitidinerequiredformaximuminhibitionofDNAmethylationinvitrodoesnotcausemajorsuppressionofDNAsynthesis.Hypomethylationmayrestorenormalfunctiontogenesthatarecriticalfordifferentiationandproliferation.Thecytotoxiceffectsofazacitidinecausethedeathofrapidlydividingcells,includingcancercellsthatarenolongerresponsivetonormalgrowthcontrolmechanisms.Non-proliferatingcellsarerelativelyinsensitivetoazacitidine.
 


References

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