Description
LomeguatribisananticancerchemotherapeuticcompoundthatisusedasapseudosubstrateforO6-methylguanine-DNAmethyltransferase(MGMT),inactivatingtheenzymeandinhibitingDNArepairacrossmanycancercelllines.Lomeguatribiscurrentlyinclinicaltrialsasaco-admiNISTeredcompoundthatincreasestheefficacyofchemotherapeuticssuchastemozolomideanddacarbazineinthetreatmentofmelanomaandothersolidtumors.Inglioblastomacells,lomeguatribdecreasesactivityofMGMTandincreasesexpressionofp53,inducingDNAfragmentationandapoptosis.
References
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TawbiHA,VillaruzL,TarhiniA,etal.InhibitionofDNArepairwithMGMTpseudosubstrates:phaseIstudyoflomeguatribincombinationwithdacarbazineinpatientswithadvancedmelanomaandothersolidtumours.BrJCancer.2011Sep6;105(6):773-7.PMID:21811257.
WatsonAJ,SabharwalA,ThorncroftM,etal.TumorO(6)-methylguanine-DNAmethyltransferaseinactivationbyorallomeguatrib.ClinCancerRes.2010Jan15;16(2):743-9.PMID:20068091.
WatsonAJ,MiddletonMR,McGownG,etal.O(6)-methylguanine-DNAmethyltransferasedepletionandDNAdamageinpatientswithmelanomatreatedwithtemozolomidealoneorwithlomeguatrib.BrJCancer.2009Apr21;100(8):1250-6.PMID:19367283.
KhanO,MiddletonMR.ThetherapeuticpotentialofO6-alkylguanineDNAalkyltransferaseinhibitors.ExpertOpinInvestigDrugs.2007Oct;16(10):1573-84.PMID:17922622.
