Discovery of Dual Kinase Inhibitors Targeting PI3Kα and AKT1: Structure-based Pharmacophore Modelling, Virtual Screening, and Molecular Docking Studies

This study aimed to identify novel dual AKT1 and PI3Kα kinase inhibitors, given their synergistic roles in driving cancer cell proliferation and survival. Structure-based pharmacophore models were developed for AKT1 and PI3Kα, and the ZincPharmer web tool was used to virtually screen the ZINC database, yielding 38 common hit compounds. SwissADME analysis identified six promising candidates based on their drug-likeness and physicochemical properties. Molecular docking simulations confirmed ZINC05999146 and ZINC04268860 as promising AKT1 and PI3Kα binders, exhibiting key hinge-region interactions with Ala230 (AKT1) and Val851 (PI3Kα). These results suggest that both compounds have potential as dual kinase inhibitors, provided that further in vitro and in vivo assessments are conducted.