Influenza-virus-IN-6-DataSheet-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEInfluenzavirus-IN-6Cat.No.:HY-152078分⼦式:C₂₇H₂₆ClNO₇分⼦量:511.95作⽤靶点:InfluenzaVirus作⽤通路:Anti-infection储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Influenzavirus-IN-6(Compound35)⼀种有效的流感聚合酶酸性蛋⽩亚内切酶N端结构域(PAN)抑制剂，IC50为0.20μM[1]。IC50&TargetIC50:0.20μM(PAN)[1]KD:56.02nM(PAN)[1]体外研究Influenzavirus-IN-6(Compound35)(48h)showsanti-influenzavirusactivityinMDCKcellswithEC50sof1.28±0.35,1.12±0.65,0.76±0.11and0.43±0.06μMagainstH1N1,H5N1,H3N2andFluB,respectively[1].Influenzavirus-IN-6(5-20μM;24h)affectsvirusreplicationbutnotvirusparticles,cells,andadsorption[1].Influenzavirus-IN-6(2.5-10μM;24h)inhibitsinfluenzaviralpolymeraseactivity[1].Influenzavirus-IN-6displayedpromisingstabilityinmouseplasma,livermicrosomes,andintestinalS9-UDPGA[1].WesternBlotAnalysis[1]CellLine:MDCKcellsConcentration:5,10and20μMIncubationTime:24hResult:Decreasednucleoprotein(NP)andmatrixprotein2(M2).RT-PCR[1]1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:MDCKcellsConcentration:2.5,5,10and20μMIncubationTime:24hResult:DecreasedtheexpressionofviralNPmRNAinawell-defineddose-dependentmanner.InhibitedcRNAsynthesisinadose-dependentfashion.体内研究Influenzavirus-IN-6(Compound35)(7.5-30mg/kg/d;i.p.;twicedailyfor7days)markedlyprotectsmicefrominfluenzavirusinfection[1].Pharmacokinetic(PK)ProfileInVivoofInfluenzavirus-IN-6(Compound35)afteraSingleDoseinRatsInVivo(n=5)a[1]parameterIV(2mg/kg)PO(10mg/kg)IP(15mg/kg)T1/2(h)0.33±0.070.82±0.161.07±0.25Tmax(h)NA0.520.45Cmax(ng/mL)1586.55±366.4892.20±36.25889.52±233.17AUC0-t(h·ng/mL)536.45±58.72164.30±26.37790.62±188.31CL(mL/min/kg)53.76±13.18NANAF%NA6.13%29.50%aIVrepresentsintravenousinjection,IPrepresentsintraperitonealinjection,andPOrepresentsthegastrointestinalroute.T1/2isthehalf-lifeofthecompoundexposureinplasma.Tmaxisthetimetakentoreachthemaximumconcentration.Cmaxrepresentsthehighestobservedconcentration.AUC(0–t)istheareaunderthecurve.CL(mL/min/kg)istheclearance.F%isthepercentbioavailability.AnimalModel:Balb/Cmice,H1N1infectionmodel[1]Dosage:0,7.5,15,and30mg/kg/dAdministration:Intraperitonealinjection,twiceperdayfor7daysResult:Exhibitedexcellentanti-IAVactivityinvivoatadoseof30mg/kg/d.Stillshowedpotentantiviralactivityinvivo,withasurvivalratioofapproximately60%againstlethalvirusinfectioninmiceat15mg/kg/d.AnimalModel:SDrats[1]Dosage:2,10or15mg/kgAdministration:IV,IP,orPO(PharmacokineticAnalysis)Result:Showedgoodpharmacokineticprofiles.REFERENCES[1].LiaoY,etal.IdentificationofN-andC-3-ModifiedLaudanosolineDerivativesasNovelInfluenzaPANEndonucleaseInhibitors.JMedChem.2022Dec15.McePdfHeight2/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECaution:Producthasnotbeenfullyvalidat