EtoposideisasemisyntheticderivativeofpodophyllotoxinandasubstanceextractedfromthemandrakerootPodophyllumpeltatum.Possessingpotentantineoplasticproperties,etoposidebindstoandinhibitstopoisomeraseIIanditsfunctioninligatingcleavedDNAmolecules,resultingintheaccumulationofsingle-ordouble-strandDNAbreaks,theinhibitionofDNAreplicationandtranscription,andapoptoticcelldeath.EtoposideactsprimarilyintheG2andSphasesofthecellcycle.Checkforactiveclinicaltrialsorclosedclinicaltrialsusingthisagent.(NCIThesaurus).MedKooCat#:100330Name:EtoposideCAS#:33419-42-0ChemicalFormula:C29H32O13ExactMass:588.18429MolecularWeight:588.55ElementalAnalysis:C,59.18;H,5.48;O,35.34Synonym:DemethylEpipodophyllotoxinEthylidineGlucoside.epipodophyllotoxin.USbrandnames:Toposar.VePesid.Foreignbrandname:Lastet.Abbreviation:EPEGCodenames:VP16;VP16213.IUPAC/ChemicalName:(5R,5aR,8aR)-9-(((2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methylhexahydropyrano[3,2-d][1,3]dioxin-6-yl)oxy)-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,5a,8a,9-tetrahydrofuro[3",4":6,7]naphtho[2,3-d][1,3]dioxol-6(8H)-oneInChiKey:VJJPUSNTGOMMGY-YLLUJYJTSA-NInChiCode:InChI=1S/C29H32O13/c1-11-36-9-20-27(40-11)24(31)25(32)29(41-20)42-26-14-7-17-16(38-10-39-17)6-13(14)21(22-15(26)8-37-28(22)33)12-4-18(34-2)23(30)19(5-12)35-3/h4-7,11,15,20-22,24-27,29-32H,8-10H2,1-3H3/t11-,15+,20-,21-,22+,24-,25-,26?,27-,29+/m1/s1SMILESCode:O=C1OC[C@]2([H])C(O[C@H]3[C@H](O)[C@@H](O)[C@]4([H])O[C@H](C)OC[C@@]4([H])O3)C5=C(C=C6OCOC6=C5)[C@@H](C7=CC(OC)=C(O)C(OC)=C7)[C@]21[H]TechnicalDataAppearance:Whitetooff-whitesolidpowderPurity:>98%(orrefertotheCertificateofAnalysis)CertificateofAnalysis:ViewCoA:currentbatch,Lot#TZC41020QCData:ViewQCdata:currentbatch,Lot#TZC41020SafetyDataSheet(MSDS):ViewMaterialSafetyDataSheet(MSDS)ShippingCondition:Shippedunderambienttemperatureasnon-hazardouschemical.ThisproductisstableenoughforafewweeksduringordinaryshippingandtimespentinCustoms.StorageCondition:Dry,darkandat0-4Cforshortterm(daystoweeks)or-20Cforlongterm(monthstoyears).Solubility:SolubleinDMSO,notinwaterShelfLife:>2yearsifstoredproperlyDrugFormulation:ThisdrugmaybeformulatedinDMSOStockSolutionStorage:0-4Cforshortterm(daystoweeks),or-20Cforlongterm(months).HarmonizedSystemCode:293490AdditionalInformationDRUGDESCRIPTIONVePesid®(etoposide)(alsocommonlyknownasVP-16)isasemisyntheticderivativeofpodophyllotoxinusedinthetreatmentofcertainneoplasticdiseases.Itis4'-demethylepipodophyllotoxin9-[4,6-O-(R)-ethylidene-β-D-glucopyranoside].Itisverysolubleinmethanolandchloroform,slightlysolubleinethanol,andsparinglysolubleinwaterandether.ItismademoremiscIBLewithwaterbymeansoforganicsolvents.Ithasamolecularweightof588.56andamolecularformulaofC29H32O13.VePesidisadmiNISTeredorally.VePesidisavailableas50mgpinkcapsules.Eachliquid-filled,softgelatincapsulecontains50mgofetoposideinavehicleconsistingofcitricacid,glycerin,purifiedwater,andpolyethyleneglycol400.Thesoftgelatincapsulescontaingelatin,glycerin,sorbitol,purifiedwater,andparabens(ethylandpropyl)withthefollowingdyesystem:ironoxide(red)andtitaniumdioxide;thecapsulesareprintedwithedibleink. CLINICALPHARMACOLOGYVePesidhasbeenshowntocausemetaphasearrestinchickfibroblasts.Itsmaineffect,however,appearstobeattheG2portionofthecellcycleinmammaliancells.Twodifferentdose-dependentresponsesareseen.Athighconcentrations(10µg/mLormore),lysisofcellsenteringmitosisisobserved.Atlowconcentrations(0.3-10µg/mL),cellsareinhibitedfromenteringprophase.Itdoesnotinterferewithmicrotubularassembly.ThepredominantmacromoleculareffectofetoposideappearstobetheinductionofDNAstrandbreaksbyaninteractionwithDNAtopoisomeraseIIortheformationoffreerADIcals.VePesidhasbeenshowntocausemetaphasearrestinchickfibroblasts.Itsmaineffect,however,appearstobeattheG2portionofthecellcycleinmammaliancells.Twodifferentdose-dependentresponsesareseen.Athighconcentrations(10µg/mLormore),lysisofcellsenteringmitosisisobserved.Atlowconcentrations(0.3-10µg/mL),cellsareinhibitedfromenteringprophase.Itdoesnotinterferewithmicrotubularassembly.ThepredominantmacromoleculareffectofetoposideappearstobetheinductionofDNAstrandbreaksbyaninteractionwithDNAtopoisomeraseIIortheformationoffreeradicals.References1:CardellicchioS,BacciG,FarinaS,GenitoriL,MassiminoM,deMartinoM,CaputoR,SardiI.Low-dosecisplatin-etoposideregimenforpatientswithopticpathwayglioma:areportoffourcasesandliteraturereview.Neuropediatrics.2014Feb;45(1):42-9.doi:10.1055/s-0033-1360482.Epub2013Nov22.Review.PubMedPMID:24272769.2:BruserudO,ReikvamH,KittangAO,AhmedAB,TvedtTH,SjoM,HatfieldKJ.High-doseetoposideinallogeneicstemcelltransplantation.CancerChemotherPharmacol.2012Dec;70(6):765-82.doi:10.1007/s00280-012-1990-z.Epub2012Oct6.Review.PubMedPMID:23053272.3:KushnerBH,ModakS,KramerK,BasuEM,RobertsSS,CheungNK.Ifosfamide,carboplatin,andetoposideforneuroblastoma:ahigh-dosesalvageregimenandreviewoftheliterature.Cancer.2013Feb1;119(3):665-71.doi:10.1002/cncr.27783.Epub2012Sep5.Review.PubMedPMID:22951749.4:EzoeS.Secondaryleukemiaassociatedwiththeanti-canceragent,etoposide,atopoisomeraseIIinhibitor.IntJEnviron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