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Small Molecule XIAP Inhibitor

22.07.2010
Apoptosis is a highly conserved process regulating the balance between cell death and proliferation for the maintenance of tissue homeostasis. Inhibitor of apoptosis proteins (IAPs) are a group of antiapoptotic proteins that

inhibit caspases, central players in the apoptotic cascade. <p> XIAP, the most potent and well characterized member of the IAP family is an inhibitor of caspase-3, -7 and -9. Through virtual screening of commercially available databases several compounds were identified as novel XIAP inhibitors. These compounds, which showed no cytotoxicity on their own, were tested in a human leukaemia cell line stably overexpressing XIAP for their ability to overcome the cells’ chemoresistance. <p>In order to develop the full therapeutic potential of our XIAP inhibitors, we currently work on the underlying apoptosis signalling mechanisms, NMR binding studies, and towards an in vivo proof of principle.

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