Pimodivir-VX-787-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPimodivirCat.No.:HY-12353ACASNo.:1629869-44-8Synonyms:VX-787分?式:C??H??F?N?O?分?量:399.39作?靶點:InfluenzaVirus作?通路:Anti-infection儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:5mg/mL(12.52mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.5038mL12.5191mL25.0382mL5mM0.5008mL2.5038mL5.0076mL10mM0.2504mL1.2519mL2.5038mL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。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?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:≥2.5mg/mL(6.26mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.26mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.26mM);ClearsolutionBIOLOGICALACTIVITY?物活性Pimodivir(VX-787)?種可?服的甲型流感病毒聚合酶抑制劑，通過抑制PB2亞起作?。體外研究Pimodivirrescuesmacrophagesfromvirus-mediateddeathatnon-cytotoxicconcentrations24hpi.TheEC50valueforPimodivirare8and12nMforA(H1N1)andA(H3N2)strains,respectively,whereastheCC50valuesare>1μM,givingselectivityindexes(SI)>125and>83forA(H1N1)andA(H3N2)strains,respectively.PimodivirsignificantlyattenuatesthetranscriptionofviralM1RNAinmacrophages,whichareinfectedwithA(H1N1)orA(H3N2)strainsfor8h.Pimodivirinhibitsthetranscriptionofviralbutnotcellulargenes.PimodivirallowssomeactivationofIAV-mediatedexpressionofseveralcellulargenes,whichareinvolvedintryptophanandnucleotidemetabolism.Pimodivirpossessesexcellentanti-IAVbutnotimmuno/metabolo-modulatingeffect[2].Pimodivir(VX-787)isverypotentagainstinfluenzaAstrains,includingpandemic2009H1N1andavianH5N1[3].Pimodivir(VX-787)showspotentactivityagainstallinfluenzaAvirusstrainstested,withanEC50rangeof0.13to3.2nM.Pimodivir-selectedPB2variantvirusesmaintainsusceptibilitytoneuraminidaseinhibitorsinvitro[4].體內(nèi)研究Pimodivir(2,6,and20mg/kg/day,p.o.)andGS4071(20mg/kg/day)completelypreventdeathintheH1N1pdmvirusinfectioninmice.Pimodivir(20mg/kg/day)ismoreeffectivethanGS4071(20mg/kg/day)inimprovingbodyweightandreducingtheseverityoflunginfection[1].Moreover,Pimodivir(VX-787)shows100%survivalina+48hdelaytotreatmentmouseinfluenzamodelat10,3and1mpk(BID×10days)whereastheSOC,GS4071,providenosurvivalbenefitinthismodelat10mpk[3].Pimodivir(VX-787;1,3,or10mg/kg,bid)providedcompletesurvival,withadose-dependentreductioninBWlossofthemice[4].PROTOCOLCellAssay[2]Thecompoundcytotoxicityandefficacytestingisperformedin96-wellplateswithmacrophagesat95%confluence.Thecompoundsareaddedtothemedium,and30minlater,thecellsareinfectedwithvirusornon-infected.ThecellviabilityisanalyzedwiththeCellTiterGloassayat24hpi.TheluminescenceisreadwithaPHERAstarFSplatereader.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalThemiceareanesthetized,andtheanimalsareinfectedintranasallywitha90-μLsuspensionofinfluenzaAdministration[1]virus.Theviruschallengeisapproximatelyfour50%mouselethalinfectiousdoses.Treatmentsaregiventwiceaday(at12hintervals)for10daysstarting2hbeforeviruschallenge.Parametersforassessingtheinfectionaresurvival,meandayofdeath,bodyweightchanges,andlunginfectionparameters(hemorrhagescore,weight,andvirustiter).Animalsareweighedindividuallyeveryotherdaythroughday21ofthe2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEinfection.Initially,thereare15micepergrouptreatedwithcompoundand25placebos.Fivemiceineachgrouparesubsequentlysacrificedfordeterminationoflunginfectionparameters.Alargernumberofplacebosareusedthancompound-treatedmicetoachievegreaterstatisticalpower,especiallyifsomeanimalsinthatgroupsurvivetheinfection.Onemousethatdiesduringthetreatmentperiodispresumedtohavediedfromtreatmenttraumabecauseitsdeathoccurswellbeforeothermicediefrominfluenza.Itisexcludedfromthetotalcounts.Animalsthatdieduringinfectionareaccountedforinthetabulardata.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?NucleicAcidsRes.2018Jan25;46(2):956-971.?AntiviralRes.2021Feb10;188:105035.?bioRxiv.2021Jan5.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].SmeeDF,etal.ActivitiesofJNJ63623872andGS4071againstinfluenzaAH1N1pdmandH3N2virusinfectionsinmice.AntiviralRes.2016Dec;136:45-50.[2].FuY,etal.JNJ872inhibitsinfluenzaAvirusreplicationwithoutalteringcellularantiviralresponses.AntiviralRes.2016Sep;133:23-31.[3].BoydMJ,etal.IsostericreplacementsofthecarboxylicacidofdrugcandidateVX-787:Effectofchargeonantiviralpotencyandkinaseactivityofazaindole-basedinfluenzaPB2inhibitors.BioorgMedChemLett.2015May1;25(9):1990-4.[4].ByrnRA,etal.PreclinicalactivityofVX-787,afirst-in-class,orallybioavailableinhibitoroftheinfluenzavirus