Tofacitinib-citrate-Tasocitinib-citrate-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETofacitinibcitrateCat.No.:HY-40354ACASNo.:540737-29-9Synonyms:Tasocitinibcitrate;CP-690550citrate分⼦式:C₂₂H₂₈N₆O₈分⼦量:504.49作⽤靶点:JAK;Apoptosis;Bacterial;Fungal;InfluenzaVirus作⽤通路:Epigenetics;JAK/STATSignaling;ProteinTyrosineKinase/RTK;StemCell/Wnt;Apoptosis;Anti-infection储存⽅式:4°C,sealedstorage,awayfrommoistureandlight*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoistureandlight)溶解性数据体外实验DMSO:28.57mg/mL(56.63mM;Needultrasonic)H2O:3.33mg/mL(6.60mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.9822mL9.9110mL19.8220mL5mM0.3964mL1.9822mL3.9644mL10mM0.1982mL0.9911mL1.9822mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoistureandlight)。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(4.96mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(4.96mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.96mM);Clearsolution4.请依序添加每种溶剂：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥1.43mg/mL(2.83mM);Clearsolution5.请依序添加每种溶剂：50%PEG300>>50%salineSolubility:2.5mg/mL(4.96mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性TofacitinibcitrateJAK3/2/1抑制剂，IC50分别为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)体外研究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].体内研究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—您⾝边的抑制剂⼤师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.户使⽤本产品发表的科研⽂献•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