Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEPeS-9Cat.No.:HY-174377分子式:C??H??O??S分子量:580.56作用靶點:AndrogenReceptor;p38MAPK;Caspase;CytochromeP450;CalciumChannel;ReactiveOxygenSpecies(ROS);Apoptosis;MitochondrialMetabolism;GLUT作用通路:VitaminDRelated/NuclearReceptor;MAPK/ERKPathway;Apoptosis;MetabolicEnzyme/Protease;MembraneTransporter/IonChannel;NeuronalSignaling;Immunology/Inflammation;NF-κB儲存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性PeS-9是一種雄激素受體(AR)降解劑，可誘導雄激素受體降解。PeS-9通過促進細胞毒性ROS產(chǎn)生，誘導線粒體和內(nèi)質(zhì)網(wǎng)應激，導致線粒體細胞色素C和AIF釋放。PeS-9可激活caspase-9和caspase-3，引起DNA片段化和細胞凋亡(apoptosis)。PeS-9具有抗前列腺癌活性，并在體內(nèi)表現(xiàn)出抗腫瘤和抗轉移活性，且副作用較小。PeS-9可用于GLUT-1過表達腫瘤的研究[1]。體外研究PeS-9(48h)showscytotoxicityincancercellswithIC50sof0.49μM(DU145),and0.58μM(LNCaP),whilehaslowcytotoxicityfornoncancercellswithIC50sof3.41μM(PNT2),3.53μM(MRC-9),11.7μM(HUVEC)and7.51μM(HEK)[1].PeS-9(0-2.5μM,4-48h)downregulatestheARsignalingpathway,producesROS,anddamagesDNAin22Rv1cells[1].PeS-9(48h)synergizeswithantiandrogenEnzalutamide(HY-70002)andPARPinhibitorOlaparib(HY-10162)withCI＜0.75in22Rv1cells[1].PeS-9(0-1μM,1h)activatestheMAPKsignalingpathwaysbyincreasingthelevelofstresskinasesp-p38,p-JNK,andp-ERKin22Rv1cells,whichcanbeantagonizedbythetestedMAPKinhibitor[1].PeS-9(0-2.5μM,1-48h)inducesapoptosisin22Rv1cellsthroughmitochondrialtargetingandcytotoxicROSinduction[1].PeS-9(0-2.5μM,1-48h)causesincreasedcytosolicCa2+levels,expansionoftheendoplasmicreticulum(ER),alteredmitochondrialmembranepermeability,andDNAdamage,asquantifiedbyanelevatedsub-G1cellpopulation[1].PeS-9(0.5-4μM,24h)inhibitstheuptakeofglucosein22Rv1cells,andthiseffectcanbeinhibitedby1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEGLUT-1inhibitorPhloretin(HY-N0142)[1].PeS-9(0.1-10μM,every5daysover20days)reducesthesurvivalfractionsoftumoroidsupondose-dependently[1].WesternBlotAnalysis[1]CellLine:22Rv1cellsConcentration:1,2μMIncubationTime:48hResult:DownregulatedAR-FL,AR-V7,PSA,IGF-1proteinsdose-dependently.RealTimeqPCR[1]CellLine:22Rv1cellsConcentration:0,0.5,1,2μMIncubationTime:48hResult:InhibitedthetranscriptionofTMPRSS2,FKBP5andPSAgenesdose-dependently.Immunofluorescence[1]CellLine:22Rv1cellsConcentration:1.25,2.5μMIncubationTime:4,24h,48hResult:InducedDNAdouble-strandbreaks(DSBs),asdemonstratedbyγH2AX/53BP1fociformationTriggeredprimaryDNAdamagewithin4hoursoftreatment,reachedpeakdamagelevelsat24hours,andshowedsignsofDNArepairactivationby48hours.WesternBlotAnalysis[1]CellLine:22Rv1cellsConcentration:0.5-4μMIncubationTime:48hResult:IncreasedBax/Bcl-2ratio(0.5,1,2,4,8μM).Downregulatedofantiapoptoticsurviving-survivin(1,2μM).Releasedcytotoxicmitochondrialproteinssuchasapoptosis-inducingfactor(AIF)andcytochromeCtocellularcytoplasm(2,4μM).Increasedthelevelofcaspase-9,caspase-3andPRAP(2,4μM).2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemE體內(nèi)研究PeS-9(27.9mg/kg,i.p.,dailyfor15days)exertsinvivoantitumorandantimetastaticactivitywithminorsideeffectsinimmunocompromisedNOD/SCIDgamma(NSG)micebearingsubcutaneouslyxenotransplantedhumanprostatecancer22Rv1cells[1].AnimalModel:NOD/SCIDgamma(NSG)8-12weeksmicebearingsubcutaneouslyxenotransplantedhumanprostatecancer22Rv1cells[1].Dosage:27.9mg/kgAdministration:Dailyi.p.administrationfor15daysResult:Reduced40.0%tumorvolumecomparedwiththecontrolgroup(1069.5mm3vs.646.6mm3).Reduced4.4-foldlungmicrometastases.Showednosignificantdifferenceontheweightsofthebody,heart,lungs,liver,andkidney.Enlargedspleenthatindicateanimmunostimulatoryeffectofthetreatment.Showednosignificantdifferenceonthewhiteandredbloodcells,platelets,hemoglobincontent,andhematocrit.Revealednosignsoftissuedamage,inflammationorgranuloma.REFERENCESBusenbenderT,etal.6-((1,4-naphthoquinone-2-yl)methyl)thio-glucoseconjugates,anoveltargetedapproachforadvancedprostatecancer.MolCancerTher.2025