Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPROTACPI3Kδdegrader-1Cat.No.:HY-176239分?式:C??H??N??O?S分?量:1150.44作?靶點(diǎn):PROTACs;PI3K;Akt;Apoptosis;Autophagy作?通路:PROTAC;PI3K/Akt/mTOR;Apoptosis;Autophagy儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性PROTACPI3Kδdegrader-1?種靶向賴氨酸的共價(jià)PI3KδPROTAC降解劑，DC50為3.98nM。PROTACPI3Kδdegrader-1具有強(qiáng)效的抗增殖活性和PI3Kδ選擇性抑制(IC50：8nM)。PROTACPI3Kδdegrader-1還能顯著降解p-AKT，誘導(dǎo)細(xì)胞周期停滯于G1期，并促進(jìn)細(xì)胞凋亡(apoptosis)和?噬(autophagy)。PROTACPI3Kδdegrader-1可有效抑制SU-DHL-6異種移植??模型中的腫瘤?長(zhǎng)[1]。粉?：PI3Kδligand(HY-169983)；藍(lán)?：VHLligaseligand(HY-112078)；??：linker(HY-W013381)IC50&TargetPI3KδPI3KδPI3KαPI3Kβ3.98nM(DC50)8nM(IC50)589nM(IC50)>10000nM(IC50)PI3Kγ605nM(IC50)體外研究PROTACPI3Kδdegrader-1(CompoundB14)(0.001-10μM,72h)hasapotentantiproliferationactivityagainstSU-DHL-6andPfeiffercells(GI50:0.17and0.35μM,respectively)[1].PROTACPI3Kδdegrader-1(10mM,0-48h)hasexcellentstabilitywith80%remainsAfter48hincubation[1].PROTACPI3Kδdegrader-1(0.1-1μM,6-24h)dose-andtime-dependentlydegradesp-AKTandp110δ(DC50:3.98nM)inSU-DHL-6cells[1].PROTACPI3Kδ(1-100nM,24h)degrader-1increasestheratioofLC3II/LC3I,bootinguptheautophagyinSU-DHL-6cells[1].PROTACPI3Kδdegrader-1(0.1-1μM,12h)hasasuperiorbindingaffinitytoVHLligaseligand,p110δandp-AKT,anditstwoderivativeshasaweakerantiproliferativeactivitycomparedtoitself(GI50:0.17vs0.90and0.87μM)[1].PROTACPI3Kδdegrader-1(100nM,12h)degradesp110δwithaubiquitin-proteasomepathwaysinSU-1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEDHL-6cells,andthiseffectisreversedbyMLN4924(HY-70062)(ubiquitinationinhibitor)andMG132(HY-13259)(proteasomeinhibitor)[1].PROTACPI3Kδdegrader-1selectivelyinhibitsPI3Kδ(IC50:8nM),with>70-foldselectivityfortheotherthreeisoforms(IC50s:>589nM,respectively)inSU-DHL-6cells[1].PROTACPI3Kδdegrader-1(1-1000nM,24h)hasastrongdegradationeffectinp110δbutweakeffectinp110αandp110βproteinlevels(DC50>1000nM)andnodegradationinp110γinSU-DHL-6cells[1].PROTACPI3Kδdegrader-1(0.01-1μM,24h)dose-dependentlyincreasestheproportionofcellsinG1phaseandsignificantlyinducescelldeathanddamageinSU-DHL-6cells[1].WesternBlotAnalysis[1]CellLine:SU-DHL-6cellsConcentration:0.1,1,3,10,30,100,1000nMIncubationTime:24hResult:Effectivelydegradedtheproteinlevelsofp110δandp-AKTat100and1000nM.Inducedthedegradationofp110δinaconcentration-dependentmanner,andthelevelsofp-AKTwereloweredcorrespondingly.IncreasedtheratioofLC3II/LC3I,bootinguptheautophagy.exhibitedmucheffectivep110δdegradationactivitywith58%and65%degradationofp110δat100and1000nM.CellCycleAnalysis[1]CellLine:SU-DHL-6cellsConcentration:0.01,0.1,1μMIncubationTime:24hResult:Dose-dependentlyincreasedtheproportionofcellsinG1phase.Potentlyinducedthecellcyclearrestat0.1μMcomparedthatat10μMofIdelalisib(HY-13026).ApoptosisAnalysis[1]CellLine:SU-DHL-6cellsConcentration:0.01,0.1,1μMIncubationTime:24hResult:Inducedasignificantamountofcelldeathanddamage.InducedmuchhighercellapoptoticpercentagesthanthatofIdelalisibwiththesamedose.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE體內(nèi)研究PROTACPI3Kδdegrader-1(CompoundB14)(2-10mg/kg,i.p.,every2daysfor21?days)demonstratessignificantantitumorefficacywithoutobvioustoxicityinSU-DHL-6xenograftmicemodel[1].AnimalModel:MaleBalb/cnudemice(4-6weeksold)wereinjectedsubcutaneouslywithSU-DHL-6cells(1×?107cells/mouse)[1].Dosage:2,10?mg/kgAdministration:i.p.,every2daysfor21?daysandthenmeasuredtumorsizeandbodyweight.Result:Exhibitedremarkableantitumorefficacywithtumorgrowthinhibitionof59.1and73.3%at2and10mg/kgdoses,respectively.Inducednosubstantialtoxiceffectswithoutsignificantbodyweightchangesanddeathupto10mg/kg.Significantlyreducedp110δproteinlevels,anddose-dependentlydecreasedtheexpressionofp-AKT.HadasignificantantiproliferativeactivitywithreductionofKi67level.Causednoobviousorgandamagewithnormalmorphologyinthetissuesofheart,liver,spleen,andkidneys.REFERENCES[1].YuanB,etal.Lysine-TargetedCovalentStrategyLeadingtotheDiscoveryofNovelPotentPROTAC-BasedPI3KδDegraders.JMedChem.2025Jun12;68(11):11437-11467.YuanB,etal.Lysine-TargetedCovalentStrategyLeadingtotheDiscoveryofNovelPotentPROTAC-BasedPI3KδDegraders.JMedChem.202