RN486isaBruton"styrosinekinase(Btk)inhibitor.RN486notonlypotentlyandselectivelyinhibitedtheBtkenzyme,butalsodisplayedfunctionalactivitiesinhumancell-basedassaysinmultiplecelltypes,blockingFcεreceptorcross-linking-induceddegranulationinmastcells(IC(50)=2.9nM),Fcγreceptorengagement-mediatedtumornecrosisfactorαproductioninmonocytes(IC(50)=7.0nM),andBcellantigenreceptor-inducedexpressionofanactivationMarker,CD69,inBcellsinwholeblood(IC(50)=21.0nM).MedKooCat#:406103Name:RN486CAS#:1242156-23-5ChemicalFormula:C35H35FN6O3ExactMass:606.27547MolecularWeight:606.69ElementalAnalysis:C,69.29;H,5.81;F,3.13;N,13.85;O,7.91Synonym:RN486;RN-486;RN486IUPAC/ChemicalName:6-cyclopropyl-8-fluoro-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-isoquinolin-1-oneInChiKey:ZTUJNJAKTLHBEX-UHFFFAOYSA-NInChiCode:InChI=1S/C35H35FN6O3/c1-39-12-14-41(15-13-39)26-8-9-32(37-19-26)38-30-18-25(20-40(2)34(30)44)27-4-3-5-31(28(27)21-43)42-11-10-23-16-24(22-6-7-22)17-29(36)33(23)35(42)45/h4-5,8-11,16-20,22,43H,6-7,12-15,21H2,1-2H3,(H,37,38)SMILESCode:O=C1N(C2=CC=CC(C(C=C3NC4=NC=C(N5CCN(C)CC5)C=C4)=CN(C)C3=O)=C2CO)C=CC6=C1C(F)=CC(C7CC7)=C6TechnicalDataAppearance:SolidpowderPurity:>98%(orrefertotheCertificateofAnalysis)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:Mina-OsorioP,LaStantJ,KeirsteadN,WhittardT,AyalaJ,StefanovaS,GarridoR,DimaanoN,HiltonH,GironM,LauKY,HangJ,PostelnekJ,KimY,MinS,PatelA,WoodsJ,RamanujamM,DeMartinoJ,NarulaS,XuD.Suppressionofglomerulonephritisinlupus-proneNZB×NZWmicebyRN486,aselectiveinhibitorofBruton'styrosinekinase.ArthritisRheum.2013Sep;65(9):2380-91.doi:10.1002/art.38047.PubMedPMID:23754328.2:XuD,KimY,PostelnekJ,VuMD,HuDQ,LiaoC,BradshawM,HsuJ,ZhangJ,PashineA,SrinivasanD,WoodsJ,LevinA,O'MahonyA,OwensTD,LouY,HillRJ,NarulaS,DeMartinoJ,FineJS.RN486,aselectiveBruton'styrosinekinaseinhibitor,abrogatesimmunehypersensitivityresponsesandarthritisinrodents.JPharmacolExpTher.2012Apr;341(1):90-103.doi:10.1124/jpet.111.187740.PubMedPMID:22228807.3:LouY,HanX,KuglstatterA,KondruRK,SweeneyZK,SothM,McIntoshJ,LitmanR,SuhJ,KocerB,DavisD,ParkJ,FrauchigerS,DewdneyN,ZecicH,TaygerlyJP,SarmaK,HongJ,HillRJ,GabrielT,GoldsteinDM,OwensTD.Structure-baseddrugdesignofRN486,apotentandselectiveBruton'styrosinekinase(BTK)inhibitor,forthetreatmentofrheumatoidarthritis.JMedChem.2015Jan8;58(1):512-6.doi:10.1021/jm500305p.PubMedPMID:24712864.4:HartkampLM,FineJS,vanEsIE,TangMW,SmithM,WoodsJ,NarulaS,DeMartinoJ,TakPP,ReedquistKA.BtkinhibitionsuppressesagoNIST-inducedhumanmacrophageactivationandinflammatorygeneexpressioninRAsynovialtissueexplants.AnnRheumDis.2015Aug;74(8):1603-11.doi:10.1136/annrheumdis-2013-204143.PubMedPMID:24764451.5:ZhaoX,HuangW,WangY,XinM,JinQ,CaiJ,TangF,ZhaoY,XiangH.DiscoveryofnovelBruton'styrosinekinase(BTK)inhibitorsbearingapyrrolo[2,3-d]pyrimidinescaffold.BioorgMedChem.2015Feb15;23(4):891-901.doi:10.1016/j.bmc.2014.10.043.PubMedPMID:25596757.6:ZhaoX,XinM,HuangW,RenY,JinQ,TangF,JiangH,WangY,YangJ,MoS,XiangH.Design,synthesisandevaluationofnovel5-phenylpyridin-2(1H)-onederivativesaspotentreversIBLeBruton'styrosinekinaseinhibitors.BioorgMedChem.2015Jan15;23(2):348-64.doi:10.1016/j.bmc.2014.11.006.PubMedPMID:25515957.7:HsuJ,GuY,TanSL,NarulaS,DeMartinoJA,LiaoC.Bruton'sTyrosineKinasemediatesplateletreceptor-inducedgenerationofmicroparticles:apotentialmechanismforamplificationofinflammatoryresponsesinrheumatoidarthritissynovialjoints.ImmunolLett.2013Feb;150(1-2):97-104.doi:10.1016/j.imlet.2012.12.007.PubMedPMID:23266841.8:WangJ,LauKY,JungJ,RavindranP,BarratFJ.Bruton'styrosinekinaseregulatesTLR9butnotTLR7signalinginhumanplasmacytoiddendriticcells.EurJImmunol.2014Apr;44(4):1130-6.doi:10.1002/eji.201344030.PubMedPMID:24375473.9:ZhaoX,HuangW,WangY,XinM,JinQ,CaiJ,TangF,ZhaoY,XiangH.Pyrrolo[2,3-b]pyridinederivativesaspotentBruton'styrosinekinaseinhibitors.BioorgMedChem.2015Aug1;23(15):4344-53.doi:10.1016/j.bmc.2015.06.023.PubMedPMID:26169764.