PH-797804-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPH-797804Cat.No.:HY-10403CASNo.:586379-66-0分⼦式:C₂₂H₁₉BrF₂N₂O₃分⼦量:477.3作⽤靶点:p38MAPK;Autophagy作⽤通路:MAPK/ERKPathway;Autophagy储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:50mg/mL(104.76mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.0951mL10.4756mL20.9512mL5mM0.4190mL2.0951mL4.1902mL10mM0.2095mL1.0476mL2.0951mL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。-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%salineSolubility:≥3mg/mL(6.29mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.24mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性PH-797804⼀种ATP竞争性的，选择性的p38α/p38β抑制剂，对p38α的IC50为26nM，Ki值为5.8nM；对p38β的Ki值为40nM，对JNK2没有抑制作⽤.IC50&TargetIC50:26nM(p38α)[1]Ki:5.8nM(p38α),40nM(p38β)[2]体外研究PH-797804blocksLPS-inducedTNF-αproductionandp38kinaseactivityinthehumanmonocyticU937cellline,withcomparableIC50of5.9nMand1.1nM.PH-797804hasnoinhibitoryeffectoneithertheJNKpathway(c-Junphosphorylation)orERKpathway(ERKphosphorylation)inU937cellsatconcentrationsupto1μM.PH-797804inhibitsRANKL-andM-CSF-inducedosteoclastformationinaconcentration-dependentmanner,withIC50of3nMinprimaryratbonemarrowcells[1].IC50valuesforPH-797804againstthefollowingtargetshavebeendeterminedtobegreaterthan200μM(unlessspecified):CDK2,ERK2,IKK1,IKK2,IKKi,MAPKAP2,MAPKAP3,MKK7(>100μM),MNK,MSK(>164μM),PRAK,RSK2,andTBK1,whichmeanstheactivityofPH-797804isspecific[2].体内研究OrallydosingofPH-797804effectivelyinhibitsacuteinflammatoryresponsesinducedbysystemicallyadministeredendotoxininbothratandcynomolgusmonkeys.PH-797804treatmentfor10daysdemonstratesrobustanti-inflammatoryactivityinchronicdiseasemodels,significantlyreducingbothjointinflammationandassociatedbonelossinstreptococcalcellwall-inducedarthritisinratsandmousecollagen-inducedarthritis.Dose-responseanalysisresultedinED50valuesof0.07mg/kgand0.095mg/kginratandcynomolgusmonkeys,respectively.PH-797804inhibitsLPS-inducedTNF-α,IL-6,andMK-2activityinadose-andconcentration-dependentmannerinahumanendotoxinchallengemodel[1].户使⽤本产品发表的科研⽂献•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•CellDeathDis.2021Oct23;12(11):994.•CellDeathDis.2018Apr27;9(5):500.•OsteoarthritisCartilage.2022May2;S1063-4584(22)00718-X.•HarvardMedicalSchoolLINCSLIBRARYSeemorecustomervalidationsonwww.MedChemEREFERENCES[1].HopeHR,etal.Anti-inflammatorypropertiesofanovelN-phenylpyridinoneinhibitorofp38mitogen-activatedproteinkinase:preclinical-to-clinicaltranslation.JPharmacolExpTher,2009,331(3),882-895.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[2].XingL,etal.Structuralbioinformatics-basedpredictionofexceptionalselectivityofp38MAPkinaseinhibitorPH-797804.Biochemistry,2009,48(27),6402-6411.McePdfHeightCaution:Producthasnot