The serine-threonine kinase B (AKT or also PKB) is a key kinase in tumorigenesis since it favors tumor progression by increasing cell proliferation, angiogenesis, apoptosis prevention and drug resistance. There are three AKT isoforms reported: AKT1, AKT2 and AKT3; these isoforms are overexpressed in some types of cancer cells; however, recent research suggests that AKT isoforms are not functionally redundant; this fact should be considered for the design of selective AKT inhibitors. Herein in this work we present an in silico approach to find potential selective inhibitors, particularly against AKT1 isoform. Using structure based-design methodology were designed 42 trisubstituted pyridines, then docking calculations were performed in Glide, AutoDock 4.2 and AutoDock Vina to find the most promising inhibitors. Molecular dynamics simulations were also performed to describe the dynamic behavior of complexes. Six molecules shown selectivity on AKT1, where the hydrophobic energy contribution together with AKT kinase domain architecture leads the selectivity.<br/>

In search of AKT inhibitors as anticancer agents, an in silico approach

253rd National Meeting (2017)

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