Abstract
X-linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitor of apoptosis proteins family of caspase inhibitors that selectively binds and inhibits caspases-3, -7 and -9, but not caspase-8. As such, XIAP blocks a substantial portion of the apoptosis pathway and is an attractive target for novel therapeutic agents for the treatment of malignancy. Antisense oligonucleotides directed against XIAP are effective in vitro and are currently being evaluated in clinical trials. Small molecule XIAP inhibitors that target the baculovirus IAP repeat (BIR) 2 or BIR 3 domain are in preclinical development and are advancing toward the clinic. This review will discuss the progress being made in developing antisense and small-molecule XIAP inhibitors.
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Abbreviations
- XIAP:
-
X-linked inhibitor of apoptosis protein
- BIR:
-
baculovirus IAP repeat
- RING:
-
really interesting new gene
- SMAC:
-
second mitochondrial activator of caspases
- AML:
-
acute myeloid leukemia
- NMR:
-
nuclear magnetic resonance
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Acknowledgements
This work was supported by grants from the Leukemia and Lymphoma Society. ADS is a Canadian Institutes of Health Research Clinician Scientist. SJR is a Fellow of the Leukemia and Lymphoma Society. We thank Fiona Scott for helpful advice and discussion, Priscilla De Luca and Francesca Pulice for assistance in preparation of the manuscript.
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Schimmer, A., Dalili, S., Batey, R. et al. Targeting XIAP for the treatment of malignancy. Cell Death Differ 13, 179–188 (2006). https://doi.org/10.1038/sj.cdd.4401826
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