Brepocitinib-P-Tosylate-PF-06700841-P-Tosylate-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEBrepocitinibP-TosylateCat.No.:HY-112708ACASNo.:2140301-96-6Synonyms:PF-06700841P-Tosylate分?式:C??H??F?N?O?S分?量:561.6作?靶點(diǎn):JAK作?通路:Epigenetics;JAK/STATSignaling;ProteinTyrosineKinase/RTK;StemCell/Wnt儲(chǔ)存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:62.5mg/mL(111.29mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.7806mL8.9031mL17.8063mL5mM0.3561mL1.7806mL3.5613mL10mM0.1781mL0.8903mL1.7806mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(3.70mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(3.70mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.70mM);ClearsolutionBIOLOGICALACTIVITY?物活性Brepocitinib(PF-06700841)P-Tosylate?種有效的JAK1和TYK2雙重抑制劑，IC50值分別為17nM和23nM。BrepocitinibP-Tosylate還分別以IC50值為77nM和6.49μM抑制JAK2和JAK3。IC50&TargetJAK1JAK2JAK317nM(IC50)77nM(IC50)6.9μM(IC50)體外研究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].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?InflammBowelDis.2020Dec9;izaa318.Seemorecustomervalidationsonwww.MedChemEREFERENCES2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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