USP1-IN-9-生命科學(xué)試劑-MCE

Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEUSP1-IN-9Cat.No.:HY-162633CASNo.:2925548-22-5分子式:C??H??F?N?O?分子量:561.56作用靶點(diǎn):Deubiquitinase作用通路:CellCycle/DNADamage儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性 USP1-IN-9(Compound1m)是可逆的且非競(jìng)爭(zhēng)性的泛素化特異性酶(USP1)抑制劑，IC50值為8.8nM。它是在ML323(HY-17543)和KSQ-4279(HY-145471)結(jié)構(gòu)的基礎(chǔ)上被設(shè)計(jì)合成為吡啶[2,3-d]嘧啶-7(8H)-1衍生物。USP1-IN-9對(duì)USP1/UAF有很好的抑制作用，并且對(duì)乳腺癌細(xì)胞有很強(qiáng)的抗增殖作用。USP1-IN-9與PARP抑制劑奧拉帕利布(HY-10162)聯(lián)合使用可增強(qiáng)對(duì)的MDA-MB-436/OP細(xì)胞的殺傷作用。USP1-IN-9有望用于癌癥領(lǐng)域的研究[1]。IC50&TargetUSP-18.8nM(IC50)體外研究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—您身邊的抑制劑大師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).體內(nèi)研究USP1-IN-9(10mg/kg,i.g.)isabsorbedrapidlyandshowsgoodmetabolicstabilityonmaleICRmice[1].合并列符號(hào)：代表后面的三列被合并：結(jié)束是列是行PharmacokineticparametersofUSP1-IN-9inMice[1]藥代動(dòng)力學(xué)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—您身邊的抑制劑大師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