Brepocitinib-P-Tosylate-PF-06700841-P-Tosylate-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBrepocitinibP-TosylateCat.No.:HY-112708ACASNo.:2140301-96-6Synonyms:PF-06700841P-Tosylate分⼦式:C₂₅H₂₉F₂N₇O₄S分⼦量:561.6作⽤靶点:JAK作⽤通路:Epigenetics;JAK/STATSignaling;ProteinTyrosineKinase/RTK;StemCell/Wnt储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:62.5mg/mL(111.29mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.7806mL8.9031mL17.8063mL5mM0.3561mL1.7806mL3.5613mL10mM0.1781mL0.8903mL1.7806mL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,awayfrommoisture)。-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.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.08mg/mL(3.70mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(3.70mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.70mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Brepocitinib(PF-06700841)P-Tosylate⼀种有效的JAK1和TYK2双重抑制剂，IC50值分别为17nM和23nM。BrepocitinibP-Tosylate还分别以IC50值为77nM和6.49μM抑制JAK2和JAK3。IC50&TargetJAK1JAK2JAK317nM(IC50)77nM(IC50)6.9μM(IC50)体外研究Brepocitinib(Compound23)potentlyinhibitsTYK2/JAK2mediatedIL-12/pSTAT4andIL-23/pSTAT3(humanwholeblood(HWB)IC50sof65and120nM,respectively).BrepocitinibhasgoodpotencyagainstIL6/pStat1intheCD3+cellularsubset(IC50of81nM),butlowerinhibitionofIL6/pSTAT3,againintheCD3+cellularsubset(IC50of641nM).BrepocitinibalsoinhibitstheJAK1/JAK3drivenγ-commonchaincytokines,representedbyIL-15/pStat5andIL-21/pSTAT3withreasonablepotency(HWBIC50sof238and204nM,respectively).BrepocitinibinhibitsEPO/pSTAT5(JAK2homodimer)inHWBspikedwithCD34+progenitorcells(IC50of577nM).IL10/pSTAT3(TYK2/JAK1)andIL27/pSTAT3(JAK1/JAK2/TYK2)arealsoinhibitedbyBrepocitinibwithIC50sof305nMand86nM,respectively[1].体内研究Brepocitinib(Compound23;3-30mg/kg;oraladministration;for7consecutivedays;femaleLewisrats)treatmentsignificantlyreducespawvolumeincreaseinadose-dependentmanner.TheplasmaconcentrationsinanimalsdosedwithBrepocitinibatpeak(30min)andtrough(24h)timeintervalspostfinaldoserespectivelyareasfollows:3mg/kg,3.54μM,0.0221μM;10mg/kg,10.95μM,0.06μM;and30mg/kg,23.89μM,0.06μM[1].AnimalModel:FemaleLewisratswithinducedarthritis[1]Dosage:3mg/kg,10mg/kg,or30mg/kgAdministration:Oraladministration;for7consecutivedaysResult:Increasedinpawvolumewassignificantlyloweranddose-dependent.户使⽤本产品发表的科研⽂献•InflammBowelDis.2020Dec9;izaa318.Seemorecustomervalidationsonwww.MedChemEREFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].FensomeA,etal.DualInhibitionofTYK2andJAK1fortheTreatmentofAutoimmuneDiseases:Discoveryof((S)-2,2-Difluorocyclopropyl)((1R,5S)-3-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone(PF-06700McePdfHeightCaution:Producthasnot