Design, Synthesis, and Biological Evaluation of a Series of Anthracene-9,10-dione Dioxime 尾-Catenin Pathway Inhibitors

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• 作者：Raffaella Soldi ; Stephen K. Horrigan ; Marek W. Cholody ; Janak Padia ; Venkataswamy Sorna ; Jared Bearss ; Glynn Gilcrease ; Kapil Bhalla ; Anupam Verma ; Hariprasad Vankayalapati ; Sunil Sharma
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：August 13, 2015
• 年：2015
• 卷：58
• 期：15
• 页码：5854-5862
• 全文大小：559K
• ISSN：1520-4804

文摘

The Wnt/尾-catenin signaling pathway plays a vital role in cell growth, the regulation, cell development, and the differentiation of normal stem cells. Constitutive activation of the Wnt/尾-catenin signaling pathway is found in many human cancers, and thus, it is an attractive target for anticancer therapy. Specific inhibitors of this pathway have been keenly researched and developed. Cell based screening of compounds library, hit-to-lead optimization, computational and structure-based design strategies resulted in the design and synthesis of a series of anthracene-9,10-dione dioxime series of compounds demonstrated potent inhibition of 尾-catenin in vitro (IC₅₀ < 10 nM, 14) and the growth of several cancer cell lines. This article discusses the potential of inhibiting the Wnt/尾-catenin signaling pathway as a therapeutic approach for cancer along with an overview of the development of specific inhibitors.