PI3Kα-IN-5-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPI3Kα-IN-5Cat.No.:HY-144829分?式:C??H??N?O?分?量:601.66作?靶點(diǎn):PI3K;mTOR作?通路:PI3K/Akt/mTOR儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性PI3Kα-IN-5(Compound6ab)?種有效的PI3Kα抑制劑，IC50值為0.7nM。PI3Kα-IN-5具有抗腫瘤活性，且具有良好的代謝穩(wěn)定性和安全性[1]。IC50&TargetPI3KαPI3KβPI3KγPI3Kδ0.7nM(IC50)4.3nM(IC50)8.7nM(IC50)27.4nM(IC50)mTOR3.3nM(IC50)體外研究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?邊的抑制劑?師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.體內(nèi)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?邊的抑制劑?師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