Small molecule inhibitors of the XIAP protein-protein interaction

The X-linked inhibitor of apoptosis proteins (XIAP) is thought to play a key role in the unchecked proliferation of cancer cells by interfering with the signaling cascade leading to cell death. The structure and mechanism of XIAP has been widely investigated and characterized over the past few years, to the point where this may be the best understood apoptosis protein inhibitor. As a result, XIAP is viewed as an attractive target for the treatment of cancer. To date, several research groups have reported on the discovery of small molecule inhibitors of this protein. This review focuses on the discovery and optimization of these leads.