PAD4-IN-4-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPAD4-IN-4Cat.No.:HY-162494分⼦式:C₃₂H₃₁ClN₆O₂分⼦量:567.08作⽤靶点:ProteinArginineDeiminase作⽤通路:Epigenetics储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性PAD4-IN-4(compound28)⼀种有效的PAD4抑制剂(IC50=0.79±0.09μM)。PAD4-IN-4通过重塑中性粒细胞表型，上调树突状细胞和M1巨噬细胞的⽐例，减少髓性抑制细胞的数量，改肿瘤免疫微环境。PAD4-IN-4可⽤于三性乳腺癌的研究[1]。IC50&TargetPAD4PAD20.79μM(IC50)2.97μM(IC50)体外研究PAD4-IN-4displayssubstantialinhibitoryactivitytowardPAD2andPAD4(IC50=2.97±0.29and0.79±0.09μM),withthebestPAD4selectivity[1].PAD4-IN-4suppressestheproliferationofTNBCcellsinvitro(4T1IC50:2.39±0.54μM;MDA-MB468IC50:2.34±0.23μM),withrelativelylowtoxicitytowardnormalbreastcells(MCF-10AIC50:8.39±0.60μM)[1].PAD4-IN-4(0.5,1,2μM;48h)hasenhancedantimetastasisactivityforTNBCcells[1].PAD4-IN-4(0.5,1,2μM;48h)isapotentPAD4inhibitorforblockinghistonecitrullinationandneutrophilextracellulartrap(NET)formation[1].CellProliferationAssay[1]CellLine:TNBCcellsConcentration:0.5,1,2μMIncubationTime:48hResult:Reducedthenumberofmetastaticcellsandwoundclosureratelessthanthatof7attheequivalentdose,indicatingthatcompound28hadenhancedantimetastasisactivity.1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEImmunofluorescence[1]CellLine:TNBCcellsandneutrophilsConcentration:0.5,1,2μMIncubationTime:48hResult:InhibitedhistonecitrullinationandNETformation.体内研究PAD4-IN-4(1,5,10mg/kg;i.v.;every2daysforatotalofninetimes)candosedependentlysuppressthelungmetastasisofTNBC.PAD4-IN-4isapromisingcandidateagainstTNBCwithoutobvioustoxicityinorthotopic4T1-lucxenograftmodelinBALB/cmice[1].PAD4-IN-4altersthetumormicroenvironmentfromasuppressiveconditiontoanantitumormilieubymodulatingtheproportionofimmunecellsandreshapingtheneutrophilphenotypeandfunction[1].PharmacokineticAnalysisinMaleSprague−Dawleyrats[1]CompoundRouteDose(mg/kg)AUC0_t(ng•h/mL)AUC0_INF(ng•h/mL)T1/2(h)Tmax(h)Cmax(ng/mL)Cl(L•h/kg)7i.v.3.514893.52178251.2571.8728i.v.3.59525.8617346.550.250.08297.71105.24AnimalModel:orthotopic4T1-lucxenograftmodelinBALB/cmice[1].Dosage:1,5,10mg/kgAdministration:Intravenousinjection(i.v.)Result:Thetumorgrowthinhibitionofthehigh-dose28-treatedgroupwas61.8%,whereasthepositivecontroldoxorubicinhydrochloridegroupreached54.6%.Hadnosignificantdifferencesinviscero−somaticratioandserumbiochemicalindices(ALT,AST,UREA,andCREA-S)wereobservedinthe28-treatedgroup.IncreasedtheproportionofmatureTANsMHC-II+TANswhereasitsuppressedtheproportionofpro-tumorphenotypesPD-L1+/MHC-II+TANsandMHC-II−TANs.REFERENCES[1].ZhuD,etal.Aβ-CarbolineDerivatePAD4InhibitorReshapesNeutrophilPhenotypeandImprovestheTumorImmuneMicroenvironmentagainstTriple-NegativeBreastCancer[J].JournalofMedicinalChemistry,2024.McePdfHeightCaution:Producthasnotbeenfullyvalidate