Inhibitors of apoptosis proteins (IAPs) antagonists
The effectors of the cell death program are enzymes called caspases, that degrade essential proteins within the cell and effectively digest the cell from the inside. Capsases can be regulated directly or indirectly by the so called inhibitor of apoptosis proteins (IAPs). It has been shown that some tumour types, such as hepatocarcinoma, are frequently associated with amplification of cIAP1 and that the tumour cells require cIAP1 to progress to full blown tumours (Zender, L., et al. Cell (2006)).
The discovery of natural mammalian IAP antagonists (by Verhagen et al (2000); Du et al (2000)) and their mode of action led directly to the development of IAP-targeting drugs that mimicked the action of the natural IAP antagonists. Our lab has been fortunate to collaborate with one of the companies involved in the development of such drugs; Tetralogic Pharmaceuticals. Together with Tetralogic Pharmaceuticals, our lab has described how these novel compounds are able to kill cancer cells and this exciting work was published in the prestigious Journal Cell (Silke, J., et al Cell (2007)).
One particularly exciting aspect of these drugs is that they specifically target cancer cells but leave normal cells relatively unaffected and we are focused on trying to discover why the drugs are so selective with the aim of further improving the utility of these new drugs.