Rucaparib-hydrochloride-AG014699-hydrochloride-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemERucaparibhydrochlorideCat.No.:HY-10617BCASNo.:773059-19-1Synonyms:AG014699hydrochloride;PF-01367338hydrochloride分⼦式:C₁₉H₁₉ClFN₃O分⼦量:359.83作⽤靶点:PARP作⽤通路:CellCycle/DNADamage;Epigenetics储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Rucaparib(AG014699)hydrochloride⼀种⼝服有效的PARP蛋⽩(PARP-1,PARP-2andPARP-3)抑制剂，对PARP-1的Ki为1.4nM。Rucaparibhydrochloride六磷酸⼰糖脱氢酶(H6PD)抑制剂。Rucaparibhydrochloride具有⽤于去势抵抗性前列腺癌(CRPC)研究的潜⼒。IC50&TargetPARP-1PARP-2PARP-31.4nM(Ki)体外研究Rucaparib(AG014699)hydrochlorideisapossibleN-demethylationmetaboliteofAG14644[1].Rucaparib(0.1,1,10,100μM;24hours)hydrochlorideiscytotoxicandhastheLC50being5ꢀμMinCapan-1(BRCA2mutant)cellsandonly100ꢀnMinMX-1(BRCA1mutant)cells[2].Theradio-sensitizationbyRucaparibhydrochlorideisduetodownstreaminhibitionofactivationofNF-κB,andisindependentofSSBrepairinhibition.RucaparibhydrochloridecantargetNF-κBactivatedbyDNAdamageandovercometoxicityobservedwithclassicalNF-κBinhibitorswithoutcompromisingothervitalinflammatoryfunctions[5].RucaparibhydrochlorideinhibitsPARP-1activityby97.1%ataconcentrationof1μMinpermeabilisedD283Medcells[6].体内研究Rucaparib(AG014699)hydrochlorideandAG14584significantlyincreaseTemozolomidetoxicity.Rucaparib(1mg/kg)hydrochloridesignificantlyincreasesTemozolomide-inducedbodyweightloss.Rucaparib(0.1mg/kg)hydrochlorideresultsina50%increaseinthetemozolomide-inducedtumorgrowthdelay[1].Rucaparib(10ꢀmg/kgfori.p.or50,150mg/kgforp.o.;dailyfor5daysperweekfor6weeks)hydrochloride1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEsignificantlyinhibitsthegrowthofthetumor,andthereisonecompletetumorregressionandtwopersistentpartialregressions[2].Rucaparib(150ꢀmg/kg;p.o.;onceperweekfor6weeksorthreetimesperweekfor6weeks)hydrochloridehasgreatestantitumoreffectwiththreecompleteregressions[2].Rucaparib(1mg/kg;i.p.;dailyfor5d)hydrochlorideenhancestheantitumoractivityoftemozolomideandindicatescompleteandsustainedtumorregressioninNB1691andSHSY5Yxenografts[6].AnimalModel:Femaleathymicnudemice,implantedSW620colorectaltumorcells(1×107cellsperanimal)s.c.[1]Dosage:0.1mg/kgincombinationwithTemozolomide(p.o.,200mg/kg),0.05,0.15,and0.5mg/kgincombinationwithTemozolomide(p.o.,68mg/kg)or10mg/kgAdministration:IP,singledosefor0.1mg/kgand10mg/kg,fivedailydosesfor0-0.5mg/kgResult:SignificantlyincreasedTemozolomidetoxicity,showedoutstandingchemosensitizationpotencyandcausedenhancementofTemozolomide-inducedtumorgrowthdelay.AnimalModel:CD-1nudemicebearingestablishedCapan-1xenografts[2]Dosage:10mg/kgor50,100and150ꢀmg/kgAdministration:IPfor10mg/kg;POfor50,100and150ꢀmg/kg,singledose(Pharmacokinetics)Result:Parentdrugwasdetectableintheplasmaonlyat30ꢀminafter10ꢀmg/kgi.pandupto4ꢀhfor50–150ꢀmg/kgp.o..Wasstilldetectableinmostmicereceivingoralrucaparibat3days.Doesnoteasilycrosstheplasmamembrane.AnimalModel:CD-1nudemicebearingestablishedCapan-1xenografts[2]Dosage:10ꢀmg/kgi.p.dailyfor5daysperweekfor6weeks,50or150ꢀmg/kgp.o.daily×fiveweekly×six,150ꢀmg/kgp.o.onceperweekfor6weeksorthreetimesperweekfor6weeks,or150ꢀmg/kgp.o.dailyforfivedaysevery3weeksAdministration:IPorPOResult:10ꢀmg/kgi.p.significantlyinhibitedthegrowthofthetumor,dailyoraladministrationat150ꢀmg/kghadanequivalenteffectontumorgrowthto10ꢀmg/kgi.p..Theschedulewiththegreatestantitumoreffectwasoraladministrationof150ꢀmg/kgonaonceweeklyschedulewiththreecompleteregressions.AnimalModel:CD-1nudemice,NB1691andSHSY5Yxenografts[6]Dosage:1mg/kgAdministration:IP,dailyfor5dincombinationwithTemozolomide(orallydaily×5atadoseof68mg/kg)2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:EnhancedtheantitumoractivityofTemozolomideandindicatedcompleteandsustainedtumorregression.户使⽤本产品发表的科研⽂献•SciTranslMed.2021May26;13(595):eabe8226.•ClinCancerRes.2017Feb15;23(4):1001-1011.•Theranostics.2020Jul25;10(21):9477-9494.•IntJMolSci.2020Feb11;21(4):1185.•Talanta.2018Apr1;180:127-132.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].ThomasHD,etal.Preclinicalselectionofanovelpoly(ADP-ribose)polymeraseinhibitorforclinicaltrial.MolCancerTher,2007,6(3),945-956.[2].JMurray,etal.Tumourcellretentionofrucaparib,sustainedPARPinhibitionandefficacyofweeklyaswellasdailyschedules.BrJCancer.2014Apr15;110(8):1977-84.[3].MattShirley,etal.Rucaparib:AReviewinOvarianCancer.TargetOncol.2019Apr;14(2):237-246.[4].JiannengLi,etal.Hexose-6-phosphatedehydrogenaseblockadereversesprostatecancerdrugresistanceinxenograftmodelsbyglucocorticoidinactivation.SciTranslMed.2021May26;13(595):eabe8226.[5].HunterJE,etal.NF-κBmediatesradio-sensitizationbythePARP-1inhibitor,AG-014699.Oncogene,2012,31(2),251-264.[6].DanielRA,etal.Inhibitionofpoly(ADP-ribose)polymerase-1enhancestemozolomideandtopotecanactivityagainst