Structure-based virtual screening approach to the discovery of phosphoinositide 3-kinase alpha inhibitors

Phosphoinositide 3-kinase alpha (PI3K alpha) has proved to be an attractive target for the development of therapeutics for the treatment of cancer. Herein we report a successful application of the structure-based virtual screening to identify the novel inhibitors of PI3K alpha. These inhibitors have desirable physicochemical properties as a drug candidate and reveal a moderate potency with IC50 values ranging from 20 to 40 mu M. Therefore, they deserve a consideration for further development by structure-activity relationship (SAR) studies to optimize the inhibitory activities. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of PI3K alpha are addressed in detail. (C) 2011 Elsevier Ltd. All rights reserved.