US9040585: Small molecule antagonists of phosphatidylinositol-3,4,5-triphosphate (PIP3) and uses thereof

Disclosed are new members of a class of non-lipid small molecule inhibitors which interfere with the interaction between phosphoinositol-3,4,5-triphosphate (PIP3) and Pleckstrin Homology (PH) domains. These molecules have a broad range of PIP3-dependent signalling events in and exert significant anti-tumor activity, with improved activity and selectivity toward particular PH domains. The small molecule inhibitors of the invention can be used alone or together with Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) or other cancer medicament to treat cancer. Small molecule inhibitors of the invention act synergistically in combination with TRAIL and with other Akt inhibitors in treating cancer. Pharmaceutical compositions and methods for treating cancer are provided.