Polθ-IN-9-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPolθ-IN-9Cat.No.:HY-179413CASNo.:3050552-13-8分⼦式:C₃₀H₃₁ClF₅N₅O₂分⼦量:624.04作⽤靶点:DNA/RNASynthesis作⽤通路:CellCycle/DNADamage储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Polθ-IN-9⼀种⼝服有效的Polθ聚合酶抑制剂(IC50=9.6nM,Kd=47.5nM)。Polθ-IN-9具有显著的选择性，对其他⼈类DNA聚合酶(Polα,Polε,Polγ,Polλ和Polμ)⽆抑制活性。Polθ-IN-9在DLD1BRCA2KO细胞中表现出强效的抗增殖活性(IC50=2.9μM)，并且对MDA-MB-436细胞⾼度敏感(IC50=4.9μM)。在MDA-MB-436异种移植瘤模型中，Polθ-IN-9与Olaparib(HY-10162)联合使⽤可增加DNA损伤积累，诱导γH2AX⽔平升⾼，并抑制肿瘤⽣长。Polθ-IN-9可⽤于研究同重组(HR)缺陷型癌症，如乳腺癌[1]。IC50&TargetHumanpolθ体外研究Polθ-IN-9(Compound33)(7days)enhancesantiproliferativeactivityinDLD1BRCA2KOcells(IC50=2.9μM),MDA-MB-436wild-typecells(IC50=4.9μM),MDA-MB-436SHLD2KOcells(IC50=2.4μM)andpancreaticcancercells(Capan-1)(IC50=13.8μM)[1].Polθ-IN-9(0.097-25μM,14days)enhancescellularpotencyinMDA-MB-436cells[1].Polθ-IN-9showsenhancedenzymaticpotencyandsignificantlyimprovedmetabolicstability,withT1/2increasingto48.3mininmouselivermicrosomesand30.5mininhumanlivermicrosomes,respectively[1].Polθ-IN-9(93.75-1500nM,14days)hasasynergisticeffectwithOlaparib(HY-10162),enhancingtheantitumoreffectofOlaparibinMDA-MB-436cells[1].CellProliferationAssay[1]CellLine:MDA-MB-436cellsConcentration:0.097,0.39,1.56,6.25,25μMIncubationTime:14days1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:ExhibitedbetteractivitycomparedtoART-558.Inducedalmostnocoloniesincellsataconcentrationof6.25μM.CellProliferationAssay[1]CellLine:MDA-MB-436cellstreatedwithOlaparib(HY-10162)Concentration:93.75,375,1500nMIncubationTime:14daysResult:ExhibitedasynergisticeffectwithOlaparibandenhanceditsantitumoractivity.ReducedtheeffectivedoseofOlaparibto12.5nM,whencoadministeredat375nMor1500nM,achievingcompleteinhibitionofcellgrowth.体内研究Polθ-IN-9(Compound33)(50mg/kg,p.o.,dailyfor25days)increasesγH2AX-positivecells,enhancesDNAdamageandinhibitstumorgrowthincombinationwithOlaparib(HY-10162),causingnosignificanttissuedamageinmajororgansinMDA-MB-436xenograftmodelinNODSCIDmice[1].AnimalModel:MDA-MB-436xenograftmodelinNODSCIDmice(6-8weeks)[1]Dosage:50mg/kgAdministration:oraladministration(p.o.),dailyfor25daysResult:Exertedonlyaweakandtransientinhibitoryeffectontumorgrowthwhenadministeredalone,withtheminorinitialeffectdiminishingovertime.Achievedaremarkabletumorgrowthinhibition(TGI)of85%incombinationwithOlaparib,greaterthanthatachievedbyOlaparibmonotherapy(10mg/kg,13%).Didnotcausesignificanttissuedamageinmajororgans,includingtheheart,liver,spleen,lung,andkidney.REFERENCES[1].YuZ,etal.RationalDesignandBiologicalEvaluationofaNovelPolθPolymeraseInhibitorforSynergisticTargetingofHR-DeficientCancers.JMedChem.2025Nov27;68(22):23801-23824.McePdfHeightCaution:Producthasnotbeenfullyvalida