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A Small Molecule Smac Mimic Potentiates TRAIL- and TNFα-Mediated Cell Death
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.
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Metadata
- Authors
- Li, L., Thomas, R. M., Suzuki, H., De Brabander, J. K., Wang, X., & Harran, P. G.
- Venue
- Science
- Published
- 2004-09-03
- Volume
- 305
- Issue
- 5689
- Pages
- 1471-1474
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1986320887
- Cited by
- 656
- References
- 2
- FWCI
- 15.74
- Type
- journal article
- Language
- en
- Open access
- closed
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