The present invention describes an improved method for screening compounds for activity in inhibiting the enzymatic activity of Akt1 protein kinase. In general, the method comprises: (1) providing a plurality of compounds suspected of having Akt1 kinase inhibitory activity (2) modeling the docking of each of the plurality of the compounds with a target binding site (3) ranking the docked compounds by goodness of fit (4) further selecting compounds (5) optionally, visually analyzing structures of compounds selected in step (4) to remove any compounds with improbable docking geometry and (6) experimentally testing the selected compounds from step (4) or step (5), if step (5) is performed, to determine their inhibitory activity against Akt1. The invention also encompasses pharmaceutical compositions including compounds whose inhibitory activity against Akt1 is discovered by the screening method, as well as methods of use of the pharmaceutical compositions to prevent and treat cancer and other conditions.
