PH-797804-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPH-797804Cat.No.:HY-10403CASNo.:586379-66-0分?式:C??H??BrF?N?O?分?量:477.3作?靶點(diǎn):p38MAPK;Autophagy作?通路:MAPK/ERKPathway;Autophagy儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:50mg/mL(104.76mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.0951mL10.4756mL20.9512mL5mM0.4190mL2.0951mL4.1902mL10mM0.2095mL1.0476mL2.0951mL請(qǐng)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(qǐng)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。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)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(qǐng)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥3mg/mL(6.29mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.24mM);ClearsolutionBIOLOGICALACTIVITY?物活性PH-797804?種ATP競(jìng)爭(zhēng)性的，選擇性的p38α/p38β抑制劑，對(duì)p38α的IC50為26nM，Ki值為5.8nM；對(duì)p38β的Ki值為40nM，對(duì)JNK2沒(méi)有抑制作?.IC50&TargetIC50:26nM(p38α)[1]Ki:5.8nM(p38α),40nM(p38β)[2]體外研究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].體內(nèi)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].戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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?邊的抑制劑?師www.MedChemE[2].XingL,etal.Structuralbioinformatics-basedpredictionofexceptionalselectivityofp38MAPkinaseinhibitorPH-797804.Biochemistry,2009,48(27),6402-6411.McePdfHeightCaution:Producthasnot