A small molecule smac mimic potentiates TRAIL- and TNFα-mediated cell death

Lin Li, Ranny Mathew Thomas, Hidetaka Suzuki, Jef K. De Brabander, Xiaodong Wang, Patrick G. Harran

Research output: Contribution to journalArticle

561 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1471-1474
Number of pages4
JournalScience
Volume305
Issue number5689
DOIs
StatePublished - Sep 3 2004

ASJC Scopus subject areas

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