Birabresib,alsoknownasOTX015andMK-8628,apotentBETbromodomianinhibitor,whichtargetstheBETbromodomainproteins2,3,and4(BRD2/3/4).BRDs2,3,and4areconsideredpotentialcancertargetsbecauseoftheirpivotalroleinregulatingthetranscriptionofgrowth-promotinggenesandcellcycleregulators.OTX015isthefirstBRD2/3/4inhibitortoenterclinicaltrials.OTX015showedantiproliferativeactivityinalargepanelofcelllinesderivedfrommatureB-celllymphoidtumorswithmedianIC50of240nmol/L,withoutsignificantdifferencesamongthedifferenthistotypes.MedKooCat#:206116Name:BirabresibCAS#:202590-98-5ChemicalFormula:C25H22ClN5O2SExactMass:491.11827MolecularWeight:491.99248ElementalAnalysis:C,61.03;H,4.51;Cl,7.21;N,14.23;O,6.50;S,6.52RelatedCAS#:204587-26-8(dihydrate) 202590-98-5  Synonym:OTX015;OTX-015;OTX015;MK-8628;MK8628;MK8628;Birabresib.IUPAC/ChemicalName:(S)-2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-N-(4-hydroxyphenyl)acetamide.InChiKey:GNMUEVRJHCWKTO-FQEVSTJZSA-NInChiCode:InChI=1S/C25H22ClN5O2S/c1-13-14(2)34-25-22(13)23(16-4-6-17(26)7-5-16)28-20(24-30-29-15(3)31(24)25)12-21(33)27-18-8-10-19(32)11-9-18/h4-11,20,32H,12H2,1-3H3,(H,27,33)/t20-/m0/s1SMILESCode:O=C(NC1=CC=C(O)C=C1)C[C@H]2C3=NN=C(C)N3C4=C(C(C)=C(C)S4)C(C5=CC=C(Cl)C=C5)=N2TechnicalDataAppearance:whitesolidpowderPurity:>98%(orrefertotheCertificateofAnalysis)CertificateofAnalysis:ViewCoA:previousbatch,Lot#TZC50528ViewCoA:currentbatch,Lot#XPR70221QCData:ViewQCdata:previousbatch,Lot#TZC50528ViewQCdata:currentbatch,Lot#XPR70221SafetyDataSheet(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:293490AdditionalInformation   References1:BoiM,TodaroM,VurchioV,YangSN,MoonJ,KweeI,RinaldiA,PanH,CrescenzoR,ChengM,CerchiettiL,ElementoO,RiveiroME,CvitkovicE,BertoniF,InghiramiG;AIRC5xMilleConsortium‘Genetics-DrivenTargetedManagementofLymphoidMalignancies’..TherapeuticefficacyofthebromodomaininhibitorOTX015/MK-8628inALK-positiveanaplasticlargecelllymphoma:analternativemodalitytoovercomeresistantphenotypes.Oncotarget.2016Nov29;7(48):79637-79653.doi:10.18632/oncotarget.12876.PubMedPMID:27793034.2:VázquezR,RiveiroME,Astorgues-XerriL,OdoreE,RezaiK,ErbaE,PaniniN,RinaldiA,KweeI,BeltrameL,BekraddaM,CvitkovicE,BertoniF,FrapolliR,D'IncalciM.ThebromodomaininhibitorOTX015(MK-8628)exertsanti-tumoractivityintriple-negativebreastcancermodelsassingleagentandincombinationwitheverolimus.Oncotarget.2016Dec7.doi:10.18632/oncotarget.13814.[Epubaheadofprint]PubMedPMID:27935867.3:CoudéMM,BraunT,BerrouJ,DupontM,BertrandS,MasseA,RaffouxE,ItzyksonR,DelordM,RiveiroME,HeraitP,BaruchelA,DombretH,GardinC.BETinhibitorOTX015targetsBRD2andBRD4anddecreasesc-MYCinacuteleukemiacells.Oncotarget.2015Jul10;6(19):17698-712.PubMedPMID:25989842;PubMedCentralPMCID:PMC4627339.4:RiveiroME,Astorgues-XerriL,VazquezR,FrapolliR,KweeI,RinaldiA,OdoreE,RezaiK,BekraddaM,InghiramiG,D'IncalciM,NoelK,CvitkovicE,RaymondE,BertoniF.OTX015(MK-8628),anovelBETinhibitor,exhibitsantitumoractivityinnon-smallcellandsmallcelllungcancermodelsharboringdifferentoncogenicmutations.Oncotarget.2016Dec20;7(51):84675-84687.doi:10.18632/oncotarget.13181.PubMedPMID:27835869.5:Berenguer-DaizéC,Astorgues-XerriL,OdoreE,CayolM,CvitkovicE,NoelK,BekraddaM,MacKenzieS,RezaiK,LokiecF,RiveiroME,OuafikL.OTX015(MK-8628),anovelBETinhibitor,displaysinvitroandinvivoantitumoreffectsaloneandincombinationwithconventionaltherapiesinglioblastomamodels.IntJCancer.2016Nov1;139(9):2047-55.doi:10.1002/ijc.30256.PubMedPMID:27388964.6:AmorimS,StathisA,GleesonM,IyengarS,MagarottoV,LeleuX,MorschhauserF,KarlinL,BroussaisF,RezaiK,HeraitP,KahattC,LokiecF,SallesG,FaconT,PalumboA,CunninghamD,ZuccaE,ThieblemontC.BromodomaininhibitorOTX015inpatientswithlymphomaormultiplemyeloma:adose-escalation,open-label,pharmacokinetic,phase1study.LancetHaematol.2016Apr;3(4):e196-204.doi:10.1016/S2352-3026(16)00021-1.PubMedPMID:27063978.7:OdoreE,LokiecF,CvitkovicE,BekraddaM,HeraitP,BourdelF,KahattC,RaffouxE,StathisA,ThieblemontC,QuesnelB,CunninghamD,RiveiroME,RezaïK.PhaseIPopulationPharmacokineticAssessmentoftheOralBromodomainInhibitorOTX015inPatientswithHaematologicMalignancies.ClinPharmacokinet.2016Mar;55(3):397-405.doi:10.1007/s40262-015-0327-6.PubMedPMID:26341814.8:BalajiN,ChinnapattuM,DixitA,SahuP,PSS,MullangiR.ValidationofanenantioselectiveLC-MS/MSmethodtoquantifyenantiomersof(±)-OTX015inmiceplasma:Lackofinvivoinversionof(-)-OTX015toitsantipode.BiomedChromatogr.2016Sep16.doi:10.1002/bmc.3853.[Epubaheadofprint]PubMedPMID:27632936.9:BoiM,GaudioE,BonettiP,KweeI,BernasconiE,TarantelliC,RinaldiA,TestoniM,CascioneL,PonzoniM,MensahAA,StathisA,StussiG,RiveiroME,HeraitP,InghiramiG,CvitkovicE,ZuccaE,BertoniF.TheBETBromodomainInhibitorOTX015AffectsPathogeneticPathwaysinPreclinicalB-cellTumorModelsandSynergizeswithTargetedDrugs.ClinCancerRes.2015Apr1;21(7):1628-38.doi:10.1158/1078-0432.CCR-14-1561.PubMedPMID:25623213.10:BerthonC,RaffouxE,ThomasX,VeyN,Gomez-RocaC,YeeK,TaussigDC,RezaiK,RoumierC,HeraitP,KahattC,QuesnelB,MichalletM,RecherC,LokiecF,PreudhommeC,DombretH.BromodomaininhibitorOTX015inpatientswithacuteleukaemia:adose-escalation,phase1study.LancetHaematol.2016Apr;3(4):e186-95.doi:10.1016/S2352-3026(15)00247-1.PubMedPMID:27063977.11:VázquezR,LicandroSA,Astorgues-XerriL,LetteraE,PaniniN,RomanoM,ErbaE,UbezioP,BelloE,LibenerR,OrecchiaS,GrossoF,RiveiroME,CvitkovicE,BekraddaM,D'IncalciM,FrapolliR.PromisinginvivoefficacyoftheBETbromodomaininhibitorOTX015/MK-8628inmalignantpleuralmesotheliomaxenografts.IntJCancer.2017Jan1;140(1):197-207.doi:10.1002/ijc.30412.PubMedPMID:27594045.12:GaudioE,TarantelliC,PonzoniM,OdoreE,RezaiK,BernasconiE,CascioneL,RinaldiA,StathisA,RiveiroE,CvitkovicE,ZuccaE,BertoniF.BromodomaininhibitorOTX015(MK-8628)combinedwithtargetedagentsshowsstronginvivoantitumoractivityinlymphoma.Oncotarget.2016Sep6;7(36):58142-58147.doi:10.18632/oncotarget.10983.PubMedPMID:27494885;PubMedCentralPMCID:PMC5295419.13:LuP,QuX,ShenY,JiangZ,WangP,ZengH,JiH,DengJ,YangX,LiX,LuH,ZhuH.TheBETinhibitorOTX015reactivateslatentHIV-1throughP-TEFb.SciRep.2016Apr12;6:24100.doi:10.1038/srep24100.PubMedPMID:27067814;PubMedCentralPMCID:PMC4828723.14:StathisA,ZuccaE,BekraddaM,Gomez-RocaC,DelordJP,deLaMotteRougeT,Uro-CosteE,deBraudF,PelosiG,FrenchCA.ClinicalResponseofCarcinomasHarboringtheBRD4-NUTOncoproteintotheTargetedBromodomainInhibitorOTX015/MK-8628.CancerDiscov.2016May;6(5):492-500.doi:10.1158/2159-8290.CD-15-1335.PubMedPMID:26976114;PubMedCentralPMCID:PMC4854801.15:HenssenA,AlthoffK,OderskyA,BeckersA,KocheR,SpelemanF,SchäfersS,BellE,NortmeyerM,WestermannF,DePreterK,FlorinA,HeukampL,SpruesselA,AstrahanseffK,LindnerS,SadowskiN,SchrammA,Astorgues-XerriL,RiveiroME,EggertA,CvitkovicE,SchulteJH.TargetingMYCN-DrivenTranscriptionByBET-BromodomainInhibition.ClinCancerRes.2016May15;22(10):2470-81.doi:10.1158/1078-0432.CCR-15-1449.PubMedPMID:26631615.16:SaenzDT,FiskusW,QianY,ManshouriT,RajapaksheK,RainaK,ColemanKG,CrewAP,ShenA,MillCP,SunB,QiuP,KADIaTM,PemmarajuN,DiNardoC,KimMS,NowakAJ,CoarfaC,CrewsCM,VerstovsekS,BhallaKN.NovelBETproteinproteolysis-targetingchimeraexertssuperiorlethalactivitythanbromodomaininhibitor(BETi)againstpost-myeloproliferativeneoplasmsecondary(s)AMLcells.Leukemia.2017Jan31.doi:10.1038/leu.2016.393.[Epubaheadofprint]PubMedPMID:28042144.17:AsanganiIA,Wilder-RomansK,DommetiVL,KrishnamurthyPM,ApelIJ,Escara-WilkeJ,PlymateSR,NavoneNM,WangS,FengFY,ChinnaiyanAM.BETBromodomainInhibitorsEnhanceEfficacyandDisruptResistancetoARAntagoNISTsintheTreatmentofProstateCancer.MolCancerRes.2016Apr;14(4):324-31.doi:10.1158/1541-7786.MCR-15-0472.PubMedPMID:26792867;PubMedCentralPMCID:PMC4834259.18:LinX,HuangX,UzielT,HesslerP,AlbertDH,Roberts-RappLA,McDanielKF,KatiWM,ShenY.HEXIM1asaRobustPharmacodynamicMarkerforMonitoringTargetEngagementofBETFamilyBromodomainInhibitorsinTumorsandSurrogateTissues.MolCancerTher.2017Feb;16(2):388-396.doi:10.1158/1535-7163.MCT-16-0475.PubMedPMID:27903752.19:LuJ,QianY,AltieriM,DongH,WangJ,RainaK,HinesJ,WinklerJD,CrewAP,ColemanK,CrewsCM.HijackingtheE3UbiquitinLigaseCereblontoEfficientlyTargetBRD4.ChemBiol.2015Jun18;22(6):755-63.doi:10.1016/j.chembiol.2015.05.009.PubMedPMID:26051217;PubMedCentralPMCID:PMC4475452.20:Pérez-PeñaJ,Serrano-HerasG,MonteroJC,Corrales-SánchezV,PandiellaA,OcañaA.InSilicoAnalysisGuidesSelectionofBETInhibitorsforTriple-NegativeBreastCancerTreatment.MolCancerTher.2016Aug;15(8):1823-33.doi:10.1158/1535-7163.MCT-16-0004.PubMedPMID:27256375.