PI3Kδ-γ-IN-3-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPI3Kδ/γ-IN-3Cat.No.:HY-150638CASNo.:2730151-31-0分⼦式:C₂₃H₂₀ClN₉O分⼦量:473.92作⽤靶点:PI3K;Apoptosis作⽤通路:PI3K/Akt/mTOR;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性PI3Kδ/γ-IN-3(Compound58)⼀种⼝服有效的PI3Kδ和PI3Kγ双抑制剂，IC50值分别为1nM和16nM。PI3Kδ/γ-IN-3诱导肿瘤细胞凋亡（apoptosis），可⽤于B细胞恶性肿瘤的研究。IC50&TargetPI3KδPI3Kγ1nM(IC50)16nM(IC50)体外研究PI3Kδ/γ-IN-3(Compound58)(72h)showsantiproliferativeactivityagainstB-celllymphoma(DLBCL)cells[1].PI3Kδ/γ-IN-3(0.5μM,24h)arrestscellcycleatG0/G1phaseinSUDHL-6andDOHH2cells[1].PI3Kδ/γ-IN-3(1.5and2μM,48h)inducescellapoptosisinSUDHL-6andDOHH2cells[1].CellProliferationAssay[1]CellLine:SUDHL-4,SUDHL-6andDOHH2cellsConcentration:IncubationTime:72hResult:ShowedantiproliferativeactivitywithIC50sof0.03±0.03,0.06±0.01and0.20±0.04μMagainstSUDHL-4,SUDHL-6andDOHH2cells,respectively.CellCycleAnalysis[1]CellLine:SUDHL-6andDOHH2cells1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEConcentration:0.5μMIncubationTime:AloneorincombinationwithIbrutininb(HY-10997)(0.5μMor1μM)for24hResult:CausedalossofG2/MphasecellsandanincreaseinthepercentageofcellsintheG0/G1phase.InducedcellcyclearrestaloneorincombinationwithIbrutinibinbothcells.ApoptosisAnalysis[1]CellLine:SUDHL-6andDOHH2cellsConcentration:1.5μMand2μMIncubationTime:AloneorincombinationwithIbrutininb(1.5μMor1μM)for48hResult:DemonstratedtheinductionofapoptosisinbothSUDHL-6andDOHH2cells,andthecombinationwasstrongerthantreatedalone.体内研究PI3Kδ/γ-IN-3(Compound58)(5and10mg/kg;p.o.;dailyfor14d)suppressesthetumorvolumeinadose-dependentmannerwithoutobvioustoxicityinmice[1].AnimalModel:Femalenonobesediabetes/severecombinedimmunodeficient(NOD/SCID)mice,6-to8-week-old,SUDHL-6xenograftmodel[1]Dosage:5and10mg/kgaloneorincombinationwith10mg/kgIbrutinibAdministration:Oraladministration,dailyfor14daysResult:Suppressedthetumorvolumeinadose-dependentmanneranddemonstratedsuperiorefficacyrelativetoIbrutinibat10mg/kgQDadministration.WhenincombinationwithIbrutinib,showedgreatertumorgrowthinhibitoryeffects.AnimalModel:SDrats[1]Dosage:5mg/kgAdministration:Oralorintravenousadministration(PharmacokineticAnalysis)Result:PKProfilesofPI3Kδ/γ-IN-3(Compound58)inMaleSDRats[1]Compounddose(mg/kg)administrationrouteCmax(ng/mL)Tmax(h)AUC0-t(h•μg/L)T1/2(h)CL(L/h/kg)Vss(L/kg)F(%)585oral3637.813.338612.579.460.79--126.55intravenous860.090.086806.922.790.752.86--PKprofiles:Cmax,maximumplasmaconcentration;Tmax,timREFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].LiuK,etal.Discovery,Optimization,andEvaluationofPotentandSelectivePI3Kδ-γDualInhibitorsfortheTreatmentofB-cellMalignancies.JMedChem.2022Jul13.McePdfHeightCaution:Producthasnotbeenfullyvalidate