Ibrutinib,alsoknownasPCI-32765,isapotentandorallyactiveBTKinhibitor.IbrutinibbindstoandinhibitsBTKactivity,preventingB-cellactivationandB-cell-mediatedsignalingandinhibitingthegrowthofmalignantBcellsthatoverexpressBTK.IbrutinibwasapprovedbytheUSFDAonNovember13,2013forthetreatmentofmantlecelllymphoma.MedKooCat#:202171Name:IbrutinibCAS#:936563-96-1ChemicalFormula:C25H24N6O2ExactMass:440.19607MolecularWeight:440.49706ElementalAnalysis:C,68.17;H,5.49;N,19.08;O,7.26Synonym:PCI32765,PCI-32765,PCI32765,Ibrutinib,ImbruvicaIUPAC/ChemicalName:(R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one.InChiKey:XYFPWWZEPKGCCK-GOSISDBHSA-NInChiCode:InChI=1S/C25H24N6O2/c1-2-21(32)30-14-6-7-18(15-30)31-25-22(24(26)27-16-28-25)23(29-31)17-10-12-20(13-11-17)33-19-8-4-3-5-9-19/h2-5,8-13,16,18H,1,6-7,14-15H2,(H2,26,27,28)/t18-/m1/s1SMILESCode:C=CC(N1C[C@H](N2N=C(C3=CC=C(OC4=CC=CC=C4)C=C3)C5=C(N)N=CN=C52)CCC1)=OTechnicalDataAppearance:whitesolidpowderPurity:>98%(orrefertotheCertificateofAnalysis)CertificateofAnalysis:ViewCoA,currentbatch,lot#TZC41120ViewCoA,previousbatch:lot#TZC40217ViewCoA,previousbatch:lot#TZC20130816QCData:ViewQCdata:previousbatch,lot#TZC40217ViewQCdate:previousbatch,lot#TZC20130816Ibrutinib1H-NMRanalysis-batchcomparison.ViewQCdata:currentbatch:Lot#TZC41120SafetyDataSheet(MSDS):ViewMaterialSafetyDataSheet(MSDS)ShippingCondition:Shippedunderambienttemperatureasnon-hazardouschemical.ThisproductisstableenoughforafewweeksduringordinaryshippingandtimespentinCustoms.StorageCondition:Dry,darkandat0-4Cforshortterm(daystoweeks)or-20Cforlongterm(monthstoyears).Solubility:SolubleinDMSOat80mg/mL,notinwaterShelfLife:>5yearsifstoredproperlyDrugFormulation:ThisdrugmaybeformulatedinDMSOStockSolutionStorage:0-4Cforshortterm(daystoweeks),or-20Cforlongterm(months).HarmonizedSystemCode:293490AdditionalInformationIbrutinibisapotentcovalentkinaseinhibitorthattargetsBTK.BTK,orBruton'styrosinekinase,isanobvioustargetfortherapyofBcelldiseasesbecauseinactivatingmutationsleadtoBcellaplasiainhumansandthediseaseX-linkedagammaglobulinemia.IbrutinibhasmodestcytotoxicityagainstCLLcellsinvitrobutalsoblockstrophicstimulifromthemicroenvironment.AswithotherinhibitorsoftheBCRpathway,ibrutinibcausesrapidnodalreductionandresponseassociatedwithrapidincreaseinlymphocytosis,whichthenreturnstobaselineovertime.TheORRofibrutinibinrelapsedrefractoryCLLis67%withPFS88%at15months.Inacohortofuntreatedpatients65yearsandover,theestimated15monthPFSis96%.Registrationtrialshavebeeninitiated,andthedifficulttaskthatremainsistodeterminewhereinthecourseofCLLtherapythisdrugwillhavethegreatestimpactandbenefitforpatients.(source:CurrHematolMaligRep.2013Mar;8(1):1-6.).    References1:MolicaS.Theemergingroleofibrutinibinthetreatmentofchroniclymphocyticleukemia.ExpertRevHematol.2013Oct;6(5):543-6.doi:10.1586/17474086.2013.831324.Epub2013Oct2.PubMedPMID:24083545.2:RushworthSA,MacEwanDJ,BowlesKM.Ibrutinibinrelapsedchroniclymphocyticleukemia.NEnglJMed.2013Sep26;369(13):1277-8.doi:10.1056/NEJMc1309710#SA2.PubMedPMID:24066760.3:NeffendorfJE,GoutI,HildebrandGD.Ibrutinibinrelapsedchroniclymphocyticleukemia.NEnglJMed.2013Sep26;369(13):1277.doi:10.1056/NEJMc1309710#SA1.PubMedPMID:24066759.4:ByrdJC,O'BrienS,JamesDF.Ibrutinibinrelapsedchroniclymphocyticleukemia.NEnglJMed.2013Sep26;369(13):1278-9.doi:10.1056/NEJMc1309710.PubMedPMID:24066758.5:CinarM,HamedaniF,MoZ,CinarB,AminHM,AlkanS.BrutontyrosinekinaseiscommonlyoverexpressedinmantlecelllymphomaanditsattenuationbyIbrutinibinducesapoptosis.LeukRes.2013Oct;37(10):1271-7.doi:10.1016/j.leukres.2013.07.028.Epub2013Aug17.PubMedPMID:23962569.6:AkinleyeA,ChenY,MukhiN,SongY,LiuD.IbrutinibandnovelBTKinhibitorsinclinicaldevelopment.JHematolOncol.2013Aug19;6:59.doi:10.1186/1756-8722-6-59.PubMedPMID:23958373;PubMedCentralPMCID:PMC3751776.7:ChangBY,FrancescoM,DeRooijMF,MagadalaP,SteggerdaSM,HuangMM,KuilA,HermanSE,ChangS,PalsST,WilsonW,WiestnerA,SpaargarenM,BuggyJJ,EliasL.EgressofCD19(+)CD5(+)cellsintoperipheralbloodfollowingtreatmentwiththeBrutontyrosinekinaseinhibitoribrutinibinmantlecelllymphomapatients.Blood.2013Oct3;122(14):2412-24.doi:10.1182/blood-2013-02-482125.Epub2013Aug12.PubMedPMID:23940282;PubMedCentralPMCID:PMC3790509.8:JainN,O'BrienS.Ibrutinib(PCI-32765)inchroniclymphocyticleukemia.HematolOncolClinNorthAm.2013Aug;27(4):851-60,x.doi:10.1016/j.hoc.2013.01.006.PubMedPMID:23915749.9:DubovskyJA,BeckwithKA,NatarajanG,WoyachJA,JaglowskiS,ZhongY,HesslerJD,LiuTM,ChangBY,LarkinKM,StefanovskiMR,ChappellDL,FrissoraFW,SmithLL,SmuckerKA,FlynnJM,JonesJA,AndritsosLA,MaddocksK,LehmanAM,FurmanR,SharmanJ,MishraA,CaligiuriMA,SatoskarAR,BuggyJJ,MuthusamyN,JohnsonAJ,ByrdJC.IbrutinibisanirreversIBLemolecularinhibitorofITKdrivingaTh1-selectivepressureinTlymphocytes.Blood.2013Oct10;122(15):2539-49.doi:10.1182/blood-2013-06-507947.Epub2013Jul25.PubMedPMID:23886836;PubMedCentralPMCID:PMC3795457.10:ByrdJC,FurmanRR,CoutreSE,FlinnIW,BurgerJA,BlumKA,GrantB,SharmanJP,ColemanM,WierdaWG,JonesJA,ZhaoW,HeeremaNA,JohnsonAJ,Su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