Design, Synthesis, and Evaluation of Potent, Nonpeptidic Mimetics of Second Mitochondria-Derived Activator of Caspases

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• 作者：Wei Sun ; Zaneta Nikolovska-Coleska ; Dongguang Qin ; Haiying Sun ; Chao-Yie Yang ; Longchuang Bai ; Su Qiu ; You Wang ; Dawei Ma ; Shaomeng Wang
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：February 12, 2009
• 年：2009
• 卷：52
• 期：3
• 页码：593-596
• 全文大小：164K
• 年卷期：v.52,no.3(February 12, 2009)
• ISSN：1520-4804

文摘

A series of new Smac mimetics have been designed, synthesized, and evaluated. The most potent compound 10 binds to XIAP, cIAP-1, and cIAP-2 BIR3 proteins with K_i of 3.9, 0.37, and 0.25 nM, respectively. Compound 10 antagonizes XIAP in a cell-free functional assay and induces rapid cIAP-1 degradation in cancer cells. Compound 10 inhibits cell growth in the MDA-MB-231 cancer cell line with an IC₅₀ of 8.9 nM.