Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETofacitinibcitrateCat.No.:HY-40354ACASNo.:540737-29-9Synonyms:Tasocitinibcitrate;CP-690550citrate分?式:C??H??N?O?分?量:504.49作?靶點:JAK;Apoptosis;Bacterial;Fungal;InfluenzaVirus作?通路:Epigenetics;JAK/STATSignaling;ProteinTyrosineKinase/RTK;StemCell/Wnt;Apoptosis;Anti-infection儲存?式:4°C,sealedstorage,awayfrommoistureandlight*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoistureandlight)溶解性數據體外實驗DMSO:28.57mg/mL(56.63mM;Needultrasonic)H2O:3.33mg/mL(6.60mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.9822mL9.9110mL19.8220mL5mM0.3964mL1.9822mL3.9644mL10mM0.1982mL0.9911mL1.9822mL請根據產品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoistureandlight)。-80°C儲存時，請在6個?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據您的實驗動物和給藥?式選擇適當的溶解?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結果的可靠性，澄的儲備液可以根據儲存條件，適當保存；體內實驗的?作液，建議您現?現配，當天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現沉淀、析出現象，可以通過加熱和/或超聲的?式助溶)1/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(4.96mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(4.96mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.96mM);Clearsolution4.請依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥1.43mg/mL(2.83mM);Clearsolution5.請依序添加每種溶劑：50%PEG300>>50%salineSolubility:2.5mg/mL(4.96mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性TofacitinibcitrateJAK3/2/1抑制劑，IC50分別為1，20和112nM。Tofacitinibcitrate具有抗，抗真菌和抗病毒活性。IC50&TargetJAK3JAK2JAK1Rock-II1nM(IC50)20nM(IC50)112nM(IC50)3400nM(IC50)Lck3870nM(IC50)體外研究Tofacitinib(CP-690550)citratebindspotentiallyatJAK3andJAK2as2.2nMand5nM(Kd).ThereportincludesadditionalbindingforTofacitinibatCamk1(Kdof5,000nM),DCamkL3(Kdof4.5nM),Mst2(Kdof4,300nM),Pkn1(Kdof200nM),Rps6ka2(Kin.Dom.2-C-terminal)(Kdof1,400nM),Rps6ka6(Kin.Dom.2-C-terminal)(Kdof1,200nM),Snark(Kdof420nM),Tnk1(Kdof640nM)andTyk2(Kdof620nM)[1].K562,KCL22,andTHP-1cellsareexposedtodifferentdosesofSTI571orJAKinhibitorsfor72htoquantifytheeffectsoftyrosinekinaseinhibitor(TKI)activity.CellgrowthinhibitionisthenevaluatedusingtheMTTassay.TheproliferationofK562andKCL22cells,butnotTHP-1cells,isinhibitedbyIMAinaconcentration-dependentmanner.TheIC50valueofIMAis0.28μMforK562and0.17μMforKCL22.AlthoughtreatmentwithTofacitinib(TOF)orINCB018424alonedoesnotsuppresscellproliferation,bothTofacitinibandINCB018424maketheK562andKCL22moresensitivetoIMA[4].體內研究AnimalsthataretreatedwithTofacitinibshowasignificantlylowerproductionofanti-drugantibodies(ADAs)comparewithPEG-treatedcontrolmice(forfiveweeksafterinitialimmunization,p[2].Basedonpreviousdose-responsestudies,adailydoseofTofacitinibof6.2mg/kgisselectedtoprovide80%inhibitionofhindpawvolumeandplasmaexposurecapableofsuppressingtheJAK1andJAK3signalingpathwaysfor>4hours[3].PROTOCOLCellAssay[4]CellsurvivalassayisperformedusingMTT.Briefly,K562,KCL22,andTHP-1cells(1×105cells/well)are2/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEplatedonto96-wellmicroplatesandtreatedwithorwithoutIMA(0.06-1.0μM)and/orTofacitinib(10-1,000nM)orRUX(10-1,000nM)for72hat37°Cinahumidified5%(v/v)CO2atmosphere.Themedium(200μL)isthenincubatedwith10μLof5mg/mlMTTsolutionfor4hat37°C.Afterbeingcentrifugedat352gfor5min,theculturemediumisremoved,and100μLofDMSOareaddedtoeachwelltodissolvetheformazan.Absorbanceismeasuredat570nmusingamicroplatereader.Theresultsareexpressedaspercentages[4].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[2]Administration[2][3]FemaleBALB/cmice(6-8weeksold)areused.MicereceiveTofacitinibinPEG300(100mg/mL)orvehiclealone(PEG300)byosmoticpumpinfusion(0.25μL/hour,28days).Fourdayspriortoimmunization,miceareanesthetizedandtheirdorsalsurfaceisshaved.Aonecmincisionismadeonthebacktocreateasubcutaneouspocketandinsertthepump.Theincisionsiteisclosedwithwoundclips.Miceareinjectedweekly(i.p.)withSS1Precombinantimmunotoxin(RIT;5μg/mouse)beginningonday0;controlmicereceivedinjectionsofsalinealone.EveryweekbeforeSS1Porvehicleimmunization,50μLofbloodisdrawntoobtainserumsamples.Seraarestoredat-80°Cuntilanalyzed.Rats[3]Adjuvant-inducedarthritis(AIA)isinducedinfemaleLewisrats.RatsarerandomizedaccordingtohindpawvolumeandassignedtoTofacitiniborvehicletreatmentregimens.Groupsof7-8ratspertreatmentgroup,andnormalnaiverats(n=4pergroup),areeuthanizedeither4hours,4days,or7daysafterbeginningtreatment(days16,20,and23afterimmunization,respectively).Once-dailyoraladministrationofvehicleorTofacitinib(6.2mg/kg)isinitiatedonday16followingimmunizationandcontinuedthroughday23.Pawvolumesarereassessed4and7daysafterthebeginningoftreatment(days20and23afterimmunization,respectively).Formicro-computedtomography(micro-CT)imaging,aswellastartrate-resistantacidphosphatase(TRAP)staininginpawtissue,AIAisinducedinaseparatecohortofLewisrats.

MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產品發表的科研?獻?AnnRheumDis.2021Sep;80(9):1201-1208.?SciTranslMed.2018Jul18;10(450).pii:eaaq1093.?BMCMed.2021Oct15;19(1):247.?CellSyst.2018Apr25;6(4):424-443.e7.?CellRep.2020Sep15;32(11):108158.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].JiangJK,etal.Examiningthechirality,conformationandselectivekinaseinhibitionof3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile(CP-690,550).JMedChem.2008Dec25;51(24):8012-8.[2].OndaM,etal.Tofacitinibsuppressesantibodyr