GDC-0834isapotentandselectiveinhibitorofBruton"styrosinekinase(BTK),investigatedasapotentialtreatmentforrheumatoidarthritis.Invitrometaboliteidentificationstudiesinhepatocytesrevealedpredominantformationofaninactivemetabolite(M1)viaamidehydrolysisinhuman.GDC-0834wasshowntobeapotentreversIBLeinhibitorofsixknownAldehydeoxidase(AO)substrateswithIC50valuesrangingfrom0.86to1.87μM.Additionally,insilicomodelingstudiessuggestthatGDC-0834iscapableofbindingintheactivesiteofAOwiththeamidebondofGDC-0834nearthemolyBDenumcofactor(MoCo),orientatedinsuchawaytoenablepotentialnucleophilicattackonthecarbonyloftheamidebondbythehydroxylofMoCo.Together,theinvitroandinsilicoresultssuggesttheinvolvementofAOintheamidehydrolysisofGDC-0834.MedKooCat#:406101Name:GDC-0834CAS#:1133432-46-8ChemicalFormula:C33H36N6O3SExactMass:596.25696MolecularWeight:596.74ElementalAnalysis:C,66.42;H,6.08;N,14.08;O,8.04;S,5.37Synonym:GDC0834;GDC-0834;GDC0834.IUPAC/ChemicalName:(R)-N-(3-(6-((4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl)amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamideInChiKey:CDOOFZZILLRUQH-GDLZYMKVSA-NInChiCode:InChI=1S/C33H36N6O3S/c1-20-24(9-7-10-25(20)36-31(40)28-18-22-8-5-6-11-27(22)43-28)26-19-39(4)33(42)30(35-26)34-23-14-12-21(13-15-23)29-32(41)38(3)17-16-37(29)2/h7,9-10,12-15,18-19,29H,5-6,8,11,16-17H2,1-4H3,(H,34,35)(H,36,40)/t29-/m1/s1SMILESCode:O=C(C1=CC(CCCC2)=C2S1)NC3=CC=CC(C(N=C4NC5=CC=C([C@H]6N(C)CCN(C)C6=O)C=C5)=CN(C)C4=O)=C3CTechnicalDataAppearance:SolidpowderPurity:>98%(orrefertotheCertificateofAnalysis)ShippingCondition:Shippedunderambienttemperatureasnon-hazardouschemical.ThisproductisstableenoughforafewweeksduringordinaryshippingandtimespentinCustoms.StorageCondition:Dry,darkandat0-4Cforshortterm(daystoweeks)or-20Cforlongterm(monthstoyears).Solubility:SolubleinDMSO,notinwaterShelfLife:>5yearsifstoredproperlyDrugFormulation:ThisdrugmaybeformulatedinDMSOStockSolutionStorage:0-4Cforshortterm(daystoweeks),or-20Cforlongterm(months).HarmonizedSystemCode:293490AdditionalInformation     References1:SodhiJK,WongS,KirkpatrickDS,LiuL,KhojastehSC,HopCE,BarrJT,JonesJP,HalladayJS.Anovelreactionmediatedbyhumanaldehydeoxidase:amidehydrolysisofGDC-0834.DrugMetabDispos.2015Jun;43(6):908-15.doi:10.1124/dmd.114.061804.Epub2015Apr6.PubMedPMID:25845827;PubMedCentralPMCID:PMC4429680.2:YoungWB,BarbosaJ,BlomgrenP,BremerMC,CrawfordJJ,DambachD,GallionS,HymowitzSG,KropfJE,LeeSH,LiuL,LubachJW,MacalusoJ,MaciejewskiP,MaurerB,MitchellSA,OrtwineDF,DiPaoloJ,ReifK,ScheerensH,SchmittA,SowellCG,WangX,WongH,XiongJM,XuJ,ZhaoZ,CurrieKS.PotentandselectiveBruton'styrosinekinaseinhibitors:discoveryofGDC-0834.BioorgMedChemLett.2015Mar15;25(6):1333-7.doi:10.1016/j.bmcl.2015.01.032.Epub2015Feb7.PubMedPMID:25701252.3:AkinleyeA,ChenY,MukhiN,SongY,LiuD.IbrutinibandnovelBTKinhibitorsinclinicaldevelopment.JHematolOncol.2013Aug19;6:59.doi:10.1186/1756-8722-6-59.Review.PubMedPMID:23958373;PubMedCentralPMCID:PMC3751776.4:RobakT,RobakE.TyrosinekinaseinhibitorsaspotentialdrugsforB-celllymphoidmalignanciesandautoimmunedisorders.ExpertOpinInvestigDrugs.2012Jul;21(7):921-47.doi:10.1517/13543784.2012.685650.Epub2012May22.Review.PubMedPMID:22612424.5:ShinYG,JonesSA,MurakamiSC,LiuL,WongH,BuonaratiMH,HopCE.Validationandapplicationofaliquidchromatography-tandemmassspectrometricmethodforthedeterminationofGDC-0834anditsmetaboliteinhumanplasmausingsemi-automated96-wellproteinprecipitation.BiomedChromatogr.2012Nov;26(11):1444-51.doi:10.1002/bmc.2716.Epub2012Feb7.PubMedPMID:22311651.6:LiuL,HalladayJS,ShinY,WongS,CoraggioM,LaH,BaumgardnerM,LeH,GopaulS,BoggsJ,KueblerP,DavisJCJr,LiaoXC,LubachJW,DeeseA,SowellCG,CurrieKS,YoungWB,KhojastehSC,HopCE,WongH.SignificantspeciesdifferenceinamidehydrolysisofGDC-0834,anovelpotentandselectiveBruton'styrosinekinaseinhibitor.DrugMetabDispos.2011Oct;39(10):1840-9.doi:10.1124/dmd.111.040840.Epub2011Jul8.PubMedPMID:21742900.7:LiuL,DiPaoloJ,BarbosaJ,RongH,ReifK,WongH.AntiarthritiseffectofanovelBruton'styrosinekinase(BTK)inhibitorinratcollagen-inducedarthritisandmechanism-basedpharmacokinetic/pharmacodynamicmodeling:relationshipsbetweeninhibitionofBTKphosphorylationandefficacy.JPharmacolExpTher.2011Jul;338(1):154-63.doi:10.1124/jpet.111.181545.Epub2011Apr26.PubMedPMID:21521773.