Zapnometinib-PD0184264-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEZapnometinibCat.No.:HY-139558CASNo.:303175-44-2Synonyms:PD0184264;ATR-002分?式:C??H?ClF?INO?分?量:409.55作?靶點(diǎn):MEK;InfluenzaVirus;Bacterial作?通路:MAPK/ERKPathway;Anti-infection儲(chǔ)存?式:4°C,protectfromlight*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:62.5mg/mL(152.61mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.4417mL12.2085mL24.4170mL5mM0.4883mL2.4417mL4.8834mL10mM0.2442mL1.2209mL2.4417mL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(protectfromlight)。-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:≥2.08mg/mL(5.08mM);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:≥2.08mg/mL(5.08mM);ClearsolutionBIOLOGICALACTIVITY?物活性Zapnometinib(PD0184264)CI-1040的活性代謝物，?種MEK抑制劑，IC50值為5.7nM。Zapnometinib具有抗流感病毒的抗病毒活性和抗活性。IC50&TargetMEK5.7nM(IC50)體外研究Zapnometinib(0.1nM-1μM)inhibitsMEK,withIC50sof30.96nM,357nM,and15nMincellfreekinaseassay,A549,MDCKcellsandhumanPBMCs[1].Zapnometinib(100μM;4h)inhibitstheIonomycin(PMA/I)-inducedphosphorylationofERK1/2inhumanPBMCs[1].Zapnometinib(1-100μM)reducestheviraltitersoftheIVH1N1pdm09,H3N2[1].WesternBlotAnalysis[1]CellLine:humanPBMCsConcentration:100μMIncubationTime:4hResult:InhibitedtheIonomycin(PMA/I)-increasedpERK1/2.體內(nèi)研究Zapnometinib(8.4-75mg/kg/day;threetimesadayp.o.)reducesthelungvirustitersandenhancessurvivalofmiceafterlethalH1N1pdm09infection[1].Zapnometinib(150mg/kg)exhibitsAUCvaluesof860.02and1953.68μg?h/mLinmicebyi.v.ororalroute,respectively[1].AnimalModel:FemaleC57BL/6mice(8weeks;21-24g)wereinfectedwithH1N1pdm09[1]Dosage:8.4,25,75mg/kg/day(2.8,8.4,25mg/kg)Administration:P.o.threetimesadayResult:Significantlyreducedthevirustiteratthedoseofeither75mg/kg/dayor25mg/kg/day.REFERENCES[1].LaureM,et,al.AntiviralefficacyagainstinfluenzavirusandpharmacokineticanalysisofanovelMEK-inhibitor,ATR-002,incellcultureandinthemousemodel.AntiviralRes.2020Jun;178:104806.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[2].HamzaH,et,al.ImprovedinvitroEfficacyofBaloxavirMarboxilAgainstInfluenzaAVirusInfectionbyCombinationTreatmentWiththeMEKInhibitorATR-002.FrontMicrobiol.2021Feb12;12:611958.[3].BruchhagenC,et,al.MetabolicconversionofCI-1040turnsacellularMEK-inhibitorintoanantibacterialcompound.SciRep.2018Jun14;8(1):9114.McePdfHeightCaution:Producthasnotbeenfullyvalidatedfor