PI3Kα-IN-5-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPI3Kα-IN-5Cat.No.:HY-144829分⼦式:C₃₀H₃₅N₉O₅分⼦量:601.66作⽤靶点:PI3K;mTOR作⽤通路:PI3K/Akt/mTOR储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性PI3Kα-IN-5(Compound6ab)⼀种有效的PI3Kα抑制剂，IC50值为0.7nM。PI3Kα-IN-5具有抗肿瘤活性，且具有良好的代谢稳定性和安全性[1]。IC50&TargetPI3KαPI3KβPI3KγPI3Kδ0.7nM(IC50)4.3nM(IC50)8.7nM(IC50)27.4nM(IC50)mTOR3.3nM(IC50)体外研究PI3Kα-IN-5(Compound6ab)(0-100µM,48or72h)exhibitspotentantiproliferativeeffectsinhumancancercellsandEGFRmutantcellswithoutobvioustoxicitytonormalcells[1].PI3Kα-IN-5(0-100µM,3h)showspotentialtoinhibitthePI3K-Akt-mTORsignalingpathway[1].PI3Kα-IN-5(0-6µM,24h)significantlyinhibitsthemigrationoftheHCT116cellsinaconcentration-dependentmanner,andinducesHCT116cellcyclearrestintheG2/Mphase[1].PI3Kα-IN-5(0-10µM,24h)exhibitspotentinhibitoryactivityontumorcellsandinducecellapoptosis[1].PI3Kα-IN-5displaysgoodstabilityinbothartificialgastrointestinalfluidsandbloodplasma[1].CellProliferationAssay[1]CellLine:MDA-MB-231,HeLa,CNE2,HCT116,MCF-7,HepG2,LO2,A431(EGFRWT),H1975(EGFRL858R/T790M),andBaF(EGFRL858R/T790M/C797S)celllinesConcentration:0-100µMIncubationTime:48h(72hforEGFRmutants)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:ShowedantiproliferativeeffectswithIC50valuesof6.48±0.52,13.44±2.16,0.07±0.01,0.11±0.09,2.22±0.13,15.14±0.54,>100,0.218±0.0016,0.217±0.018,and0.217±0.035µMagainstMDA-MB-231,HeLa,CNE2,HCT116,MCF-7,HepG2,LO2,A431(EGFRWT),H1975(EGFRL858R/T790M),andBaF3(EGFRL858R/T790M/C797S)cells,respectively.WesternBlotAnalysis[1]CellLine:HCT116Concentration:10and100µMIncubationTime:3hResult:ImmenselypreventedthephosphorylationofAkt(p-Akt-S473)andp70S6K(p-p70S6K-T389).CellCycleAnalysis[1]CellLine:HCT116Concentration:1.5,3and6µMIncubationTime:24hResult:ThepercentageofcellsintheG2/Mphaseincreasedfrom22.20%to30.80%.ApoptosisAnalysis[1]CellLine:HCT116Concentration:2.5,5and10µMIncubationTime:24hResult:Thepercentageoftotalapoptosiscellsincreasedto39.10%,23.01%and35.2%atconcentrationsof2.5,5and10µM,respectively.体内研究PI3Kα-IN-5(Compound6ab)(20mg/kg;i.v.)exhibitssignificantantitumorefficacywithgoodsafetyprofiles[1].AnimalModel:FemaleBalb/Cnudemice(HCT116xenograftmodel)[1]Dosage:20mg/kg,10µL/gAdministration:Intravenousinjection2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:ProducedsignificantantitumorefficacyagainstHCT-116modelwithatumorgrowthinhibition(TGI)valueof41.6%onday19.AnimalModel:SDrats[1]Dosage:20mg/kgAdministration:Intravenousinjection(PharmacokineticAssay)Result:PharmacokineticparametersofPI3Kα-IN-5afterasingle20mg/kgivdoseinSDratsaCompoundAUC(0-72)(µg/L*h)AUC(0-inf)(µg/L*h)MRT(h)T1/2(h)Tmax(h)Cl(mL/min/kg)Vss(L/kg)PI3Kα-IN-529950±138030575±145610.4±0.219.0±1.30.0310.9±0.517.9±1.3aAUC:areaundertheplasmaconcentrationtimecurve;MRT:meanresonancetime;T1/2:half-time;Tmax:peaktime;Cl:clearance;Vss:volumeofdistributionatsteadystate.REFERENCES[1].Chun-FengWu,etal.Synthesisandbioevaluationofdiarylureaderivativesaspotentialantitumoragentsforthetreatmentofhumancolorectalcancer.EurJMedChem.2022Feb5;229:114055.McePdfHeightCaution:Producthas