USP1-IN-9-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemEUSP1-IN-9Cat.No.:HY-162633CASNo.:2925548-22-5分子式:C₂₉H₂₆F₃N₇O₂分子量:561.56作用靶点:Deubiquitinase作用通路:CellCycle/DNADamage储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性 USP1-IN-9(Compound1m)是可逆的且非竞争性的泛素化特异性酶(USP1)抑制剂，IC50值为8.8nM。它是在ML323(HY-17543)和KSQ-4279(HY-145471)结构的基础上被设计合成为吡啶[2,3-d]嘧啶-7(8H)-1衍生物。USP1-IN-9对USP1/UAF有很好的抑制作用，并且对乳腺癌细胞有很强的抗增殖作用。USP1-IN-9与PARP抑制剂奥拉帕利布(HY-10162)联合使用可增强对的MDA-MB-436/OP细胞的杀伤作用。USP1-IN-9有望用于癌症领域的研究[1]。IC50&TargetUSP-18.8nM(IC50)体外研究USP1-IN-9(20,100,500nM,24h)elevatesthemonoubiquitinatedPCNA(Ub-PCNA)levelsinadose-dependentmanner.USP1-IN-9demonstratesanincreaseinUb-PCNAevenatconcentrationsaslowas20nMinnonsmallcelllungcancer(NSCLC)cells[1].USP1-IN-9(0.5μM,7days)exhibitesasubstantialinhibitionofthecolonyformingcapacityofNSCLCcells[1].USP1-IN-9(1nM,24h)aloneresultsinaminorcellcyclearrestinolaparib-resistantbreastcancercells,whereasthecombinationofolaparib(HY-10162)andUSP1-IN-9caninducecellcyclearrest[1].USP1-IN-9(100nM,7days)combinedwitholaparibcanpotentiatebreastcancercellstoolaparibkilling[1].WesternBlotAnalysis[1]CellLine:NSCLCcellsConcentration:20,100,500nMIncubationTime:24h1/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEResult:ElevatedthemonoubiquitinatedPCNA(Ub-PCNA)levelsinadose-dependentmannerinNSCLCcells.CellViabilityAssay[1]CellLine:NSCLCcellsConcentration:0.5nMIncubationTime:7daysResult:Exhibitedasubstantialinhibitionofthecolonyformingcapacityofbreastcancercellscomparedtotheuntreatedcontrol.CellCycleAnalysis[1]CellLine:Breastcancercellsandolaparib-resistantbreastcancercellsConcentration:1nMIncubationTime:24hResult:ResultedinaminorincreaseincellswithintheSphase,whereasthecombinationofolaparibandUSP1-IN-9ledtoanaccumulationofcellswithintheSphaseandG2/Mphase.CellViabilityAssay[1]CellLine:Olaparib-resistantbreastcancercellsConcentration:100nMIncubationTime:7daysResult:Aloneexhibitedareductionof30%anddidnotdemonstratesignificantcellkilling.Theinhibitionrateofcolonyformationwasfurtherelevatedto50%combinedwithUSP1-IN-9andolaparib(100nM).体内研究USP1-IN-9(10mg/kg,i.g.)isabsorbedrapidlyandshowsgoodmetabolicstabilityonmaleICRmice[1].合并列符号：代表后面的三列被合并：结束是列是行PharmacokineticparametersofUSP1-IN-9inMice[1]药代动力学分析[1]ParametersDose(mg/kg,po)Tmax(h)Cmax(ng/mL)AUC0-t(ng·h/mL)T1/2(h)USP1-IN-9100.254780±209035,800±13,5007.61±4.672/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEAnimalModel:maleICRmiceDosage:10mg/kgAdministration:i.g.,asingledoseResult:Wasabsorbedrapidlyandshowedgoodmetabolicstabilitywithalonghalf-lifeof7.61honmaleICRmice.REFERENCES[1]LiH,etal.Design,synthesis,andbiologicalevaluationofpyrido[2,3-d]pyrimidin-7(8H)-onederivativesaspotentUSP1inhibitors[j].EurJMedChem.2024Jun14;275:116568./38889606/[1]LiH,etal.Design,synthesis,andbiologicalevaluationofpyrido[2,3-d]pyrimidin-7(8H)-onederivativesaspotentUSP1inhibitors[j].EurJMedChem.2024Jun14;275:116568./38889606/[1]LiH,etal.Design,synthesis,andbiologicalevaluationofpyrido[2,3-d]pyrimidin-7(8H)-onederivativesaspotentUSP1inhibitors[J].EurJMedChem.2024Jun14;275:116568./38889606/LiH,etal.Design,synthesis,andbiologicalevaluationofpyrido[2,3-d]pyrimidin-7(8H)-onederivativesaspotentUSP1inhibitors[J].EurJMedChem.2024Jun14;275:116568.LiH,etal.Design,synthesis,andbiologicalevaluationofpyrido[2,3-d]pyrimidin-7(8H)-onederivativesaspotentUSP1inhibitors[J].EurJMedChem.2024Jun14;275:116568.McePdfHeightCaut