A Small Molecule Smac Mimic Potentiates TRAIL- and TNFα-Mediated Cell Death
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- 3 September 2004
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 305 (5689) , 1471-1474
- https://doi.org/10.1126/science.1098231
Abstract
We describe the synthesis and properties of a small molecule mimic of Smac, a pro-apoptotic protein that functions by relieving inhibitor-of-apoptosis protein (IAP)–mediated suppression of caspase activity. The compound binds to X chromosome– encoded IAP (XIAP), cellular IAP 1 (cIAP-1), and cellular IAP 2 (cIAP-2) and synergizes with both tumor necrosis factor α (TNFα) and TNF-related apoptosis-inducing ligand (TRAIL) to potently induce caspase activation and apoptosis in human cancer cells. The molecule has allowed a temporal, unbiased evaluation of the roles that IAP proteins play during signaling from TRAIL and TNF receptors. The compound is also a lead structure for the development of IAP antagonists potentially useful as therapy for cancer and inflammatory diseases.Keywords
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