MedKooCat#:201050
Name:Vadimezan(DMXAA)
CAS#:117570-53-3
ChemicalFormula:C17H14O4
ExactMass:282.08921
MolecularWeight:282.29
ElementalAnalysis:C,72.33;H,5.00;O,22.67.
Synonym:ASA404;ASA404;ASA404;AS1404;AS1404;AS1404;DMXAA;Vadimezan
IUPAC/ChemicalName:(5,6-Dimethyl-9-oxo-9H-xanthen-4-yl)-aceticacid
InChiKey:XGOYIMQSIKSOBS-UHFFFAOYSA-N
InChiCode:InChI=1S/C17H14O4/c1-9-6-7-13-15(20)12-5-3-4-11(8-14(18)19)17(12)21-16(13)10(9)2/h4-7H,8H2,1-2H3,(H,18,19)
SMILESCode:O=C(O)CC1=CC=CC(C2=O)=C1OC3=C2C=CC(C)=C3C
VadimezanorASA404(originallyDMXAA)isatumor-vasculardisruptingagent(tumor-VDA)thatattacksthebloodsupplyofacanceroustumortocausetumorregression. ASA404wasdiscoveredbyBruceBaguleyandWilliamDennyandtheirteamsattheAucklandCancerSocietyResearchCentreattheUniversityofAucklandinNewZealand.[6]ItwaslicensedtoAntisomain2001.Novartisacquiredtheworldwiderightsforitin2007anditisbeingdevelopedbyAntisomaandNovartis.Seewikipedia.
Novartisannouncedtoday(November11,2010)thattheclinicaltrialprogramfortheinvestigationalcancertreatmentASA404(vadimezan)willbediscontinuedandresourceswillbereallocatedtoothercompoundsintheoncologypipeline.ThedecisionwasmadeafterinterimresultsfromaPhaseIIItrialshowedthatASA404wouldnotlikelymeettheprimaryendpointofsignificantlyextendingoverallsurvivalwhenusedincombinationwithchemotherapyforthesecond-linetreatmentofpatientswithadvancednon-smallcelllungcancer(NSCLC).(source:http://www.novartis.com/newsroom/media-releases/en/2010/1461276.shtml).
(source:http://www.novartis.com/newsroom/media-releases/en/2010/1461276.shtml).
1:LouYC,KaoYF,ChinKH,ChenJK,TuJL,ChenC,ChouSH.Backboneresonanceassignmentsofthe54kDadimericC-terminaldomainofmurineSTINGincomplexwithDMXAA.BiomolNMRAssign.2014Dec9.[Epubaheadofprint]PubMedPMID:25487675.
2:GaoP,ZillingerT,WangW,AscanoM,DaiP,HartmannG,TuschlT,DengL,BarchetW,PatelDJ.Binding-pocketandlid-regionsubstitutionsrenderhumanSTINGsensitivetothespecies-specificdrugDMXAA.CellRep.2014Sep25;8(6):1668-76.doi:10.1016/j.celrep.2014.08.010.Epub2014Sep4.PubMedPMID:25199835.
3:DowneyCM,AghaeiM,SchwendenerRA,JirikFR.DMXAAcausestumorsite-specificvasculardisruptioninmurinenon-smallcelllungcancer,andliketheendogenousnon-canonicalcyclicdinucleotideSTINGagoNIST,2'3'-cGAMP,inducesM2macrophagerepolarization.PLoSOne.2014Jun18;9(6):e99988.doi:10.1371/journal.pone.0099988.eCollection2014.PubMedPMID:24940883;PubMedCentralPMCID:PMC4062468.
4:YungR,SeyfoddinV,GuiseC,TijonoS,McGregorA,ConnorB,ChingLM.EfficacyagainstsubcutaneousorintracranialmurineGL261gliomasinrelationtotheconcentrationofthevascular-disruptingagent,5,6-dimethylxanthenone-4-aceticacid(DMXAA),inthebrainandplasma.CancerChemotherPharmacol.2014Mar;73(3):639-49.doi:10.1007/s00280-014-2395-y.Epub2014Jan30.PubMedPMID:24477604.
5:GaoP,AscanoM,ZillingerT,WangW,DaiP,SerganovAA,GaffneyBL,ShumanS,JonesRA,DengL,HartmannG,BarchetW,TuschlT,PatelDJ.Structure-functionanalysisofSTINGactivationbyc[G(2',5')pA(3',5')p]andtargetingbyantiviralDMXAA.Cell.2013Aug15;154(4):748-62.doi:10.1016/j.cell.2013.07.023.Epub2013Aug1.PubMedPMID:23910378.
6:TangCK,AoshiT,JounaiN,ItoJ,OhataK,KobiyamaK,DessaillyBH,KurodaE,AkiraS,MizuguchiK,CobanC,IshiiKJ.ThechemotherapeuticagentDMXAAasauniqueIRF3-dependenttype-2vaccineadjuvant.PLoSOne.2013;8(3):e60038.doi:10.1371/journal.pone.0060038.Epub2013Mar21.PubMedPMID:23555875;PubMedCentralPMCID:PMC3605442.
7:TijonoSM,GuoK,HenareK,PalmerBD,WangLC,AlbeldaSM,ChingLM.Identificationofhuman-selectiveanaloguesofthevascular-disruptingagent5,6-dimethylxanthenone-4-aceticacid(DMXAA).BrJCancer.2013Apr2;108(6):1306-15.doi:10.1038/bjc.2013.101.Epub2013Mar12.PubMedPMID:23481185;PubMedCentralPMCID:PMC3619269.
8:YeniceliD,DengX,AdamsE,Dogrukol-AkD,VanSchepdaelA.DevelopmentofaCD-MEKCmethodforinvestigatingthemetabolismoftamoxifenbyflavin-containingmonooxygenasesandtheinhibitoryeffectsofmethimazole,nicotineandDMXAA.Electrophoresis.2013Feb;34(3):463-70.doi:10.1002/elps.201200356.Epub2012Dec26.PubMedPMID:23161341.
9:PrantnerD,PerkinsDJ,LaiW,WilliamsMS,SharmaS,FitzgeraldKA,VogelSN.5,6-Dimethylxanthenone-4-aceticacid(DMXAA)activatesstimulatorofinterferongene(STING)-dependentinnateimmunepathwaysandisregulatedbymitochondrialmembranepotential.JBiolChem.2012Nov16;287(47):39776-88.doi:10.1074/jbc.M112.382986.Epub2012Oct1.PubMedPMID:23027866;PubMedCentralPMCID:PMC3501038.
10:HenareK,WangL,WangLC,ThomsenL,TijonoS,ChenCJ,WinklerS,DunbarPR,PrintC,ChingLM.Dissectionofstromalandcancercell-derivedsignalsinmelanomaxenograftsbeforeandaftertreatmentwithDMXAA.BrJCancer.2012Mar13;106(6):1134-47.doi:10.1038/bjc.2012.63.PubMedPMID:22415295;PubMedCentralPMCID:PMC3304430.
11:McKeageMJ,JamesonMB;AS1404-201StudyGroupInvestigators.Comparativeoutcomesofsquamousandnon-squamousnon-smallcelllungcancer(NSCLC)patientsinphaseIIstudiesofASA404(DMXAA)-retrospectiveanalysisofpooleddata.JThoracDis.2010Dec;2(4):199-204.doi:10.3978/j.issn.2072-1439.2010.02.04.1.PubMedPMID:22263047;PubMedCentralPMCID:PMC3256477.
12:BuchananCM,ShihJH,AstinJW,RewcastleGW,FlanaganJU,CrosierPS,ShepherdPR.DMXAA(Vadimezan,ASA404)isamulti-kinaseinhibitortargetingVEGFR2inparticular.ClinSci(Lond).2012May1;122(10):449-57.doi:10.1042/CS20110412.PubMedPMID:22142330.
13:JamesonMB,HeadM.Pharmacokineticevaluationofvadimezan(ASA404,5,6-dimethylxanthenone-4-aceticacid,DMXAA).ExpertOpinDrugMetabToxicol.2011Oct;7(10):1315-26.doi:10.1517/17425255.2011.614389.Epub2011Aug26.Review.PubMedPMID:21870897.
14:MarysaelT,NiY,LerutE,deWitteP.InfluenceofthevasculardamagingagentsDMXAAandZD6126onhypericindistributionandaccumulationinRIF-1tumors.JCancerResClinOncol.2011Nov;137(11):1619-27.doi:10.1007/s00432-011-1032-y.Epub2011Aug21.PubMedPMID:21858709.
15:SunJ,WangLC,FridlenderZG,KapoorV,ChengG,ChingLM,AlbeldaSM.Activationofmitogen-activatedproteinkinasesby5,6-dimethylxanthenone-4-aceticacid(DMXAA)playsanimportantroleinmacrophagestimulation.BiochemPharmacol.2011Nov1;82(9):1175-85.doi:10.1016/j.bcp.2011.07.086.Epub2011Jul26.PubMedPMID:21819972;PubMedCentralPMCID:PMC3191304.
16:PengS,MonieA,PangX,HungCF,WuTC.VasculardisruptingagentDMXAAenhancestheantitumoreffectsgeneratedbytherapeuticHPVDNAvaccines.JBiomedSci.2011Mar8;18:21.doi:10.1186/1423-0127-18-21.PubMedPMID:21385449;PubMedCentralPMCID:PMC3062584.
17:ShireyKA,NhuQM,YimKC,RobertsZJ,TeijaroJR,FarberDL,BlancoJC,VogelSN.Theanti-tumoragent,5,6-dimethylxanthenone-4-aceticacid(DMXAA),inducesIFN-beta-mediatedantiviralactivityinvitroandinvivo.JLeukocBiol.2011Mar;89(3):351-7.doi:10.1189/jlb.0410216.Epub2010Nov17.PubMedPMID:21084628;PubMedCentralPMCID:PMC3040469.
18:BaguleyBC,SiemannDW.TemporalaspectsoftheactionofASA404(vadimezan;DMXAA).ExpertOpinInvestigDrugs.2010Nov;19(11):1413-25.doi:10.1517/13543784.2010.529128.Review.PubMedPMID:20964495;PubMedCentralPMCID:PMC3583340.
19:BrauerR,WangLC,WoonST,BridewellDJ,HenareK,MalingerD,PalmerBD,VogelSN,KiedaC,TijonoSM,ChingLM.LabelingofoxidizableproteinswithaphotoactivatableanalogoftheantitumoragentDMXAA:evidenceforredoxsignalinginitsmodeofaction.Neoplasia.2010Sep;12(9):755-65.PubMedPMID:20824052;PubMedCentralPMCID:PMC2933696.
20:HeadM,JamesonMB.Thedevelopmentofthetumorvascular-disruptingagentASA404(vadimezan,DMXAA):currentstatusandfutureopportunities.ExpertOpinInvestigDrugs.2010Feb;19(2):295-304.doi:10.1517/13543780903540214.PubMedPMID:20050824.
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