Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETalacotuzumabCat.No.:HY-P99395CASNo.:1826831-79-1Synonyms:JNJ56022473;CSL362作?靶點:InterleukinRelated作?通路:Immunology/Inflammation儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Talacotuzumab(JNJ56022473;CSL362)?種IgG1型完全?化的CD123中和單克隆抗體，含有修飾的Fc結(jié)構(gòu)。Talacotuzumab對CD123、CD32b/c、CD16-158F、CD16-158V的KD分別為0.43nM、188nM、46nM、16.8nM。Talacotuzumab抑制IL-3與CD123的結(jié)合，從?拮抗靶細胞中的IL-3信號傳導(dǎo)。Talacotuzumab使Fc區(qū)發(fā)?突變以增加對CD16(FcγRIIIa)的親和?，從?增強抗體依賴性細胞介導(dǎo)的細胞毒性(ADCC)。Talacotuzumab在體內(nèi)?常有效地減少急性髓性??病(AML)異種移植??模型中的??病細胞?長。體外研究Talacotuzumab(JNJ56022473;CSL362)stronglymediatesADCCofTF-1cellswithanic50of5ng/ml(33pM)[1].Talacotuzumab(1μg/ml;pretreatmentfor24hours)inhibitsTLR7-stimulated(Imiquimod;HY-B0180;0.5μM;for6days)andTLR9-stimulated(CpGC;0.5μM;for6days)IFN-αproductioninbothSLEdonorsandhealthydonorsplasmacytoiddendriticcells(pDCs)andbasophils,whereasTLR4-stimulated(LPS;HY-D1056;10μg/ml)productionisnotsignificantlyreduced.TalacotuzumabinhibitsTLR7-andTLR9-inducedplasmablastexpansionandproliferationbydepletionofplasmacytoiddendriticcells(pDCs)[2].體內(nèi)研究Talacotuzumab(JNJ56022473;CSL362;300μg;ip;thriceweeklyfor5weeks)resultsinasignificantdelayintumorgrowthcomparedwithanisotypecontrolinacutemyeloidleukaemiamicexenografts[1].Talacotuzumab(1,10,30mg/kg;s.c.;singleinjection)hasmaximalserumconcentrationsat48hoursof~12,190,and380μg/mlatdosesof1,10,and30mg/kginnaivecynomolgusmonkeys,respectively[2].AnimalModel:Nonobesediabetic/severecombinedimmunodeficiencymiceinjectedintravenouslyAMLxenograftcells(AML-5)[1]1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEDosage:300μgAdministration:IP;thriceweeklyfor5weeksResult:Resultedinasignificantdelayintumorgrowthcomparedwithanisotypecontrol.REFERENCES[1].SJBusfield,etal.Targetingofacutemyeloidleukemiainvitroandinvivowithananti-CD123mAbengineeredforoptimalADCC.Leukemia.2014Nov;28(11):2213-21.[2].ShereenOon,etal.Acytotoxicanti-IL-3Rαantibodytargetskeycellsandcytokinesimplicatedinsystemiclupuserythematosus.JCIInsight.2016May5;1(6):e86131.[3].ErwinMLee,etal.EfficacyofanFc-modifiedanti-CD123antibody(CSL362)combinedwithchemotherapyinxenograftmodelsofacutemyelogenousleukemiainimmunodeficientmice.Haematologica.2015Jul;100(7):914-26.[4].LHXie,etal.CD123targetvalidationandpreclinicalevaluationofADCCactivityofanti-CD123antibodyCSL362incombinationwithNKsfromAMLpatientsinremission.BloodCancerJ.2017Jun2;7(6):e567.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedical