RTx-303-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemERTx-303Cat.No.:HY-179219SCASNo.:3035072-99-9分⼦式:C₂₄H₂₂D₃F₇N₄O₄分⼦量:569.49作⽤靶点:DNA/RNASynthesis作⽤通路:CellCycle/DNADamage储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性RTx-303⼀种⼝服有效的选择性DNA聚合酶θ(Polθ)抑制剂(IC50=5.1nM)。RTx-303具有显著的细胞活性，并能显著增强PARP抑制剂在BRCA1/2突变细胞和患者来的异种移植模型中的活性。RTx-303可⽤于BRCA2突变型乳腺癌的研究[1]。体外研究RTx-303significantlyinhibitsPolθ-polactivity,buthasnosignificanteffectonotherDNApolymerases(suchasPolβ,Polη,Polγ,etc)[1].RTx-303(10μM)showsnosignificantinhibitionofmostkinases(%activity>90%),andonlymildinhibitionofafewkinases,suchasPASK(75%activity)andATR/ATRIP(77%activity)[1].RTx-303showsanIC50of81.2nMagainstHRDcells(HCT116BRCA2-/-)and>1280nMagainstHR-proficientcells(HCT116BRCA2+/+),demonstrating>100-foldselectivity[1].RTx-303(5μM,5days)incombinationwithOlaparib(HY-10162)significantlyreducestheIC50ofID8BRCA2-/-cells(from2μMto0.12μM)andrestoresOlaparibsensitivityinPARPi-resistantcells[1].体内研究RTx-303(60mg/kg,p.o.,twicedailyfor28-42days)effectivelyinhibitsthegrowthofBRCA2-mutatedtumorsinmousemodels,whetherusedaloneorincombinationwithPARPi,andnosignificantweightlossisobserved,indicatingahighsafetyprofile[1].RTx-303(60mg/kg,p.o.,twicedailyfor56days),incombinationwithOlaparib,canpreventacquiredresistancetoPARPiinBRCA1-mutanttumorsinMDA-MB-436xenograftmice[1].AnimalModel:FortheBR-05-0566(BR-05-0568)BRCA2mutantPDXstudy,-30mm3tumorfragmentwasimplantedsubcutaneouslyintofemaleBALB/cmice6-8weeksold[1].Dosage:60mg/kg1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAdministration:P.o.,twicedailyfor28days(BR-05-0566)to42days(BR-05-0568)Result:BR-05-0566model:Significantlyinhibitedtumorgrowth(comparedtothevehiclegroup);combinedwitholaparib,itledtotumorregression;tumorvolumereduction>80%inthecombinationgroup.BR-05-0568model:Combinedwithtalazoparib,itresultedin100%completetumorelimination.Nosignificantweightlosswasobservedinanygroup.AnimalModel:10×106MDA-MB-436(bearingBRCA1-Mutant)cellswereinjectedwithMatrigelsubcutaneouslyintofemaleBALB/cmice,6-8weeksold[1].Dosage:60mg/kgAdministration:P.o.,twicedailyfor56daysResult:TreatedwithOlaparib,tumorsregressedrapidlyandtherewasnorecurrence.REFERENCES[1].ChandramoulyG,etal.RTx-303,anOrallyBioavailablePolθPolymeraseInhibitorThatPotentiatesPARPInhibitorsinBRCAMutantTumors.JMedChem.2025Nov13;68(21):22196-22215.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapp