A small molecule Smac mimic potentiates TRAIL-and TNFα-mediated cell death
L Li, RM Thomas, H Suzuki, JK De Brabander, X Wang… - Science, 2004 - science.org
L Li, RM Thomas, H Suzuki, JK De Brabander, X Wang, PG Harran
Science, 2004•science.orgWe 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 …
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 …
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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