夏普
细胞凋亡
肿瘤坏死因子α
小分子
程序性细胞死亡
细胞生物学
半胱氨酸蛋白酶
癌症研究
受体
化学
半胱氨酸蛋白酶8
信号转导
凋亡抑制因子
分子生物学
生物
免疫学
生物化学
作者
Li Lin,Ranny Mathew Thomas,Hidetaka Suzuki,Jef K. De Brabander,Xiaodong Wang,Patrick G. Harran
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2004-09-03
卷期号:305 (5689): 1471-1474
被引量:629
标识
DOI:10.1126/science.1098231
摘要
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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