Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPI3Kδ/HDAC6-IN-1Cat.No.:HY-174396CASNo.:3075011-99-0分?式:C??H??N??O?分?量:650.73作?靶點(diǎn):PI3K;HDAC;Bcl-2Family;Caspase;ReactiveOxygen

Species(ROS);Apoptosis;HistoneMethyltransferase;

Microtubule/Tubulin作?通路:PI3K/Akt/mTOR;CellCycle/DNADamage;Epigenetics;Apoptosis;Immunology/Inflammation;MetabolicEnzyme/Protease;NF-κB;Cytoskeleton儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性PI3Kδ/HDAC6-IN-1(Compound22E)PI3Kδ和HDAC6?服有效的雙重有效抑制劑，IC50值分別為2.4nM和6.2nM。PI3Kδ/HDAC6-IN-1對(duì)?霍奇?淋巴瘤(NHL)細(xì)胞表現(xiàn)出強(qiáng)?的抗增殖作?，并具有體內(nèi)抗腫瘤活性且?明顯毒性。PI3Kδ/HDAC6-IN-1將細(xì)胞周期阻滯于G0/G1期，并誘導(dǎo)細(xì)胞凋亡(apoptosis)。PI3Kδ/HDAC6-IN-1阻斷PI3K/AKT/mTOR信號(hào)通路，并增加α-微管蛋?和組蛋?H3的??；?平[1]。IC50&TargetPI3KδHDAC62.4nM(IC50)6.2nM(IC50)體外研究PI3Kδ/HDAC6-IN-1(compound22E)(0.1nM-10μM,24-120h)showsinhibitoryactivityagainstbothPI3KδandHDAC6withIC50valuesof2.4nMand6.4nM,andexhibitsantiproliferativeactivityagainstJEKO-1cells[1].PI3Kδ/HDAC6-IN-1(10-30μM,45°C-85°C)improvesthermalstabilityofPI3KδandHDAC6[1].PI3Kδ/HDAC6-IN-1(0.1-10μM,4days)inhibitstheproliferationofNHLcells,withIC50valuesof34nM(SU-DHL-6cells)and53nM(JEKO-1cells)[1].PI3Kδ/HDAC6-IN-1(0.3-9μM,24h)inducesG0/G1phasearrestintheSU-DHL-6andJEKO-1cells[1].PI3Kδ/HDAC6-IN-1(0.3-9μM,72h)inducesapoptosis(AnnexinVpositive)concentration-dependentintheSU-DHL-6andJEKO-1cells[1].PI3Kδ/HDAC6-IN-1(0.3-9μM,12h)inhibitsPI3KandHDAC-relatedproteinsatthecellularlevelintheSU-DHL-6andJEKO-1cells[1].1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellCycleAnalysis[1]CellLine:SU-DHL-6andJEKO-1cellsConcentration:0.3μM,1μM,3μM,9μMIncubationTime:24hResult:IncreasedtheratioofcellsinG0/G1phase,blockedcancercellsintheG0/G1phase.DownregulatedcyclinD1,cyclinE1,CDK6,CDK4,andCDK2proteins.ApoptosisAnalysis[1]CellLine:SU-DHL-6andJEKO-1cellsConcentration:0.3μM,1μM,3μM,9μMIncubationTime:72hResult:InducedAnnexinVpositivity,downregulatedtheanti-apoptoticproteinBCL-2,increasedlevelsofcleavedPARPandcleavedcaspase-3.Inducedaconcentration-dependentincreaseintheROS-positivecellcountinJEKO-1cells.WesternBlotAnalysis[1]CellLine:SU-DHL-6andJEKO-1cellsConcentration:0.3μM,1μM,3μM,9μMIncubationTime:12hResult:InhibitedhosphorylationofdownstreamsignalingproteinsofPI3K,includingAKT,P70S6K,and4EBP1,aswellastheoncogene-encodedproteinc-MYC,whilehavingnoeffectontotalproteinlevels.IncreasedhistoneH3andα-tubulinacetylationlevels.體內(nèi)研究PI3Kδ/HDAC6-IN-1(Compound22E)(25mg/kg,p.o.,onceaday,21days)hasanti-tumorpotential,inhibitsPI3KpathwayandHDAC-relatedproteinsinSU-DHL-6andJEKO-1tumorxenograftmodelsinNOD-SCIDmice[1].AnimalModel:SU-DHL-6andJEKO-1tumorxenograftmodelsinNOD-SCIDmice[1]Dosage:25mg/kgAdministration:p.o.,21daysResult:Reducedtumorgrowth,exhibitedantitumoractivity,withcorrespondingTGIratesof2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE69.42%intheSU-DHL-6modeland67.56%intheJEKO-1model.Reducedp-AKTlevelsandincreasedacetyl-α-tubulinlevels,reducedKi-67levelsandincreasedcleavedcaspase-3levels.REFERENCES[1].ZuoY,etal.Design,synthesis,andbiologicalevaluationofnovelPI3Kδ/HDAC6dualinhibitorsforthetreatmentofnon-Hodgkin'slymphoma.EurJMedChem.2025Oct15;296:117852.McePdfHeightCaution:Producth