Disclosed are a new class of non-lipid small molecule inhibitors which interfere with the interaction between PIP3 and pleckstrin homology domains. These molecules target a broad range of PIP3-dependent signaling events in vitro and exert significant anti-tumor activity in vivo. 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 in treating cancer. Pharmaceutical compositions and methods for treating cancer are provided.
