TY - JOUR
T1 - A small molecule smac mimic potentiates TRAIL- and TNFα-mediated cell death
AU - Li, Lin
AU - Thomas, Ranny Mathew
AU - Suzuki, Hidetaka
AU - De Brabander, Jef K.
AU - Wang, Xiaodong
AU - Harran, Patrick G.
PY - 2004/9/3
Y1 - 2004/9/3
N2 - 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.
AB - 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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U2 - 10.1126/science.1098231
DO - 10.1126/science.1098231
M3 - Article
C2 - 15353805
AN - SCOPUS:4444243683
SN - 0036-8075
VL - 305
SP - 1471
EP - 1474
JO - Science
JF - Science
IS - 5689
ER -