PX-316-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPX-316Cat.No.:HY-119134CASNo.:253440-95-8分⼦式:C₂₈H₅₇O₁₀P分⼦量:584.72作⽤靶点:Akt作⽤通路:PI3K/Akt/mTOR储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性PX-316⼀种Akt抑制剂。PX-316可使Akt磷酸化，但不抑制PDK1或PKC的磷酸化。PX-316能特异性地增加⼀组线粒体相关因的表达。PX-316可⽤于结肠癌和乳腺癌的研究[1]。IC50&TargetAkt体外研究PX-316(0-15μM,2h)specificallyinhibitsAkt(IC50=1.7μM)activationinHT-29humancoloncancercellswithoutaffectingupstreamkinasePDK1orrelatedkinasePKC[1].PX-316(0.5-20μM,3days)inhibitstheproliferationofMCF-7andHT-29cells[1].WesternBlotAnalysis[1]CellLine:HT-29humancoloncancercellsConcentration:0μM,5μM,10μM,15μMIncubationTime:2hResult:InhibitedEGF-inducedAktphosphorylation(phosphorylationofSer473site)inaconcentration-dependentmannerwithanIC50valueof1.7μM,butdidnotinhibitPDK1phosphorylation(Ser241site)orPKCphosphorylation(Thr638/641site).体内研究PX-316(37.5-150mg/kg,i.p.,once)effectivelyinhibitstheAktsignalingpathwayanditsdownstreamtargetsinHT-29cellsxenograftmice,andtheinhibitoryeffectismaintainedevenaftermultipleadministrations[1].PX-316(50-150mg/kg,i.p.,oncefor4-10days)demonstratesdose-andregimen-dependentantitumor1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEactivityintwodifferentmicexenograftmodelsofhumantumors(MCF-7andHT-29)[1].AnimalModel:HT-29coloncancercells(107)wereinjectedsubcutaneouslyintotheflanksofmaleseverecombinedimmunodeficient(scid)mice[1].Dosage:37.5mg/kg,75mg/kg,150mg/kgAdministration:I.p.,onceResult:Asingleadministrationof150mg/kginhibitedAkt(Ser473)phosphorylationintumorsbyupto78%at10hours,recoveringto34%inhibitionafter48hours.Thehalf-maximalinhibitorydose(ID50)forAktphosphorylationintumorswas80mg/kg,whiletheID50fornormaltissue(spleen)was128mg/kg.Ataconcentrationof150mg/kg,phosphorylationofGSK-3β(Ser9),adownstreamtargetofAkt,wasalsoinhibited,withinhibitionratesof53%and77%at5hoursand24hours,respectively.Atadoseof75mg/kg,whetheradministeredoncedailyfor5consecutivedaysoronceevery3daysfor5consecutivedays,Aktactivitywasconsistentlyinhibited(inhibitionrateof70%-80%).AnimalModel:MCF-7humanbreastcancercells(107cells)weremixedwithMatrigelandsubcutaneouslyinjectedintotheflankoffemaleSCIDmice.Onedaybeforetumorcellinoculation,miceweresubcutaneouslyimplantedwith60-daysustained-release17-β-estradiolpelletstosupportthegrowthofthisestrogen-dependenttumor[1].Dosage:50mg/kg,75mg/kg,100mg/kgAdministration:I.p.,oncedailyfor10days,10daysand5days,respectivelyResult:75mg/kgshowedagoodinhibitoryeffect(T/C=20%),while100mg/kgshowedaslightlyweakereffect(T/C=39%).AnimalModel:HT-29humancoloncancercells(107cells)weresubcutaneouslyinjectedintotheflankofSCIDmice[1].Dosage:100mg/kg,150mg/kgAdministration:I.p.,oncedailyfor4daysResult:Causedgrowthinhibitionof5-dayHT-29coloncancerxenograftswhenadministeredfor4daysIPat150mg/kg/day(T/C33.3%,P<0.05)butnoactivityat100mg/kg/day.REFERENCES[1].MeuilletEJ,etal.InvivomolecularpharmacologyandantitumoractivityofthetargetedAktinhibitorPX-316.OncolRes.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2004;14(10):513-27.McePdfHeightCaution:Producthas