Identification and Design of Potent Leads for AKT1: Pharmacophore Modeling and Virtual Screening

AKT1 is a serine threonine kinase, which is emerging as a vital target for the treatment of cancer. The aim of this study was to identify novel scaffolds and utilize them in designing potent AKT1 inhibitors. Pharmacophore hypothesis was developed. The high correlating model (r=0.979) with one hydrogen bond acceptor, one hydrogen bond donor, one hydrophobic and one ring aromatic feature was selected, validated and used in virtual screening. Hit compounds were subjected to various drug-like filters and molecular docking studies. Finally threestructurally diverse compounds with high GOLDfitness scores and interactions with critical active site amino acids were identified. These final hits can be developed as potent virtual leads with effective AKT1 inhibitor designing.