ROCK2-IN-13-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEROCK2-IN-13Cat.No.:HY-179498分⼦式:C₁₈H₁₁F₃N₄S分⼦量:372.37作⽤靶点:FOXO;PTEN;ROCK;EpigeneticReaderDomain;PI3K;Akt;Apoptosis作⽤通路:MetabolicEnzyme/Protease;PI3K/Akt/mTOR;CellCycle/DNADamage;Cytoskeleton;StemCell/Wnt;TGF-beta/Smad;Epigenetics;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性ROCK2-IN-13⼀种选择性ROCK2抑制剂。ROCK2-IN-13通过抑制ROCK2激酶活性并降低其核内表达，破坏ROCK2与转录共激活因⼦p300和PGC1α的相互作⽤，进⽽抑制致癌因转录。ROCK2-IN-13能激活FOXO1驱动的PTEN表达，从⽽抑制PI3K/Akt通路、诱导G2/M期细胞周期阻滞并促进细胞凋亡(apoptosis)。ROCK2-IN-13由此消除了维持致癌信号传导的ROCK2核转录功能，并恢复了抑癌性PTEN/FOXO1轴。ROCK2-IN-13可⽤于前列腺癌的相关研究[1]。IC50&TargetROCKIIFOXO1PI3KAkt体外研究ROCK2-IN-13(compound25)(30μM,24h)exhibitsstrongantiproliferativeactivity(84.5%inhibition)inhumanprostatecancercells(PC-3),demonstratespotentandconsistentefficacywithGI50valuesof3.7μMinPC-3cellsand3.9μMinLNCaPcells,andshowssubstantiallylowercytotoxicitytowardnormalcells(CC50s:55.0μMforCCD841and41.8μMforHEK-293)[1].ROCK2-IN-13reducestheexpressionofthehighlyexpressedoncoproteinFOXA2(HNF-3β)alongwiththelessabundantFOXO1inPC-3cells[1].ROCK2-IN-13(1-10μM)inducesaconcentration-dependentdecreaseinFOXA2mRNAandanincreaseinFOXO1mRNA,leadingtoreducednuclearFOXA2protein,enhancedFOXO1nuclearaccumulation,decreasedcytoplasmicFOXO1phosphorylation,andultimatelysuppressingthePI3K/AktaxisviaPTENupregulation,whichsubsequentlyelevatesp27expressionandtheBax/Bcl-2ratiowhilereducingcyclinD1levels,inPC-3andLNCaPcells[1].ROCK2-IN-13(1-10μM,24h)reducestheproportionsofcellsintheG1andSphasesandinducesamarkedaccumulationofcellsintheG2/MphaseinPC-3cells[1].ROCK2-IN-13(1-10μM)inducesaconcentration-dependentinductionofapoptosiswiththeproportionof1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEearlyandlateapoptoticcellsreaching15.7%and8.7%,respectively,at10μMinPC-3cells[1].ROCK2-IN-13(1-10μM,48h)suppressesthePI3K/AktsignalingpathwaypredominantlyviaPTENactivation,ratherthanthroughdirectEGFRinhibitioninPC-3cells[1].ROCK2-IN-13(1-10μM,48h)inducesaconcentration-dependentincreaseinPGC-1αmRNA,significantlyreducesthemRNAexpressionofbothROCK1andROCK2withagreatereffectonROCK2,decreasesnuclearROCK2proteinwhileleavingcytoplasmicROCK1unchanged,enhancesthetranscriptionofFOXO1byrecruitingRNApolymeraseIIandPGC-1αtoitspromoter,andfacilitatesPTENtranscriptionbypromotingthebindingofRNApolymeraseIIandkeyco-regulators(ROCK1/2,PGC-1α,andp300)tothePTENpromoterinPC-3cells[1].CellProliferationAssay[1]CellLine:PC-3cellsConcentration:30μMIncubationTime:24hResult:Exhibitedthestrongtantiproliferativeactivityachievinginhibitionratesexceeding80%.CellCycleAnalysis[1]CellLine:PC-3cellsConcentration:1,3,and10μMIncubationTime:24hResult:ReducedtheproportionsofcellsintheG1andSphasesandinducedamarkedaccumulationofcellsintheG2/Mphase.CellViabilityAssay[1]CellLine:PC-3cellsConcentration:1,3,and10μMIncubationTime:48hResult:ExhibitedgreatercytotoxicitythanGefitinib(HY-50895)(aselectiveEGFRinhibitor)andtheircombinedtreatmentsynergisticallyreducedPC-3cellviability.体内研究ROCK2-IN-13(compound25)(30and50mg/kg,i.p.,dailyfor26days)significantlysuppressestumorgrowthinaprostatecancerxenograftmodel[1].AnimalModel:PC-3cells(1×106,s.c.)induce-BALB/cnudemice(Seven-week-old)[1]Dosage:30and50mg/kg2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAdministration:i.p.,dailyfor26daysResult:Significantlyanddose-dependentlyreducedtumorgrowthinthexenograftmodel.Hadanti-tumoreffectafter26daysofdailyadministrationat3mg/kg.Producedasignificantlylowertumorweightthandocetaxel.REFERENCES[1].LeeJ,etal.InhibitionofnuclearROCK2byanovelthioureaderivativeinducespotentantitumoreffectsthroughPTEN/FOXO1pathwayrestorationinprostatecancer.BioorgChem.2025Dec;167:1092