Differential Targeting of Human Topoisomerase II Isoforms with Small Molecules

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• 作者：Angelica Mariani ; Alexandra Bartoli ; Mandeep Atwal ; Ka C. Lee ; Caroline A. Austin ; Rapha毛l Rodriguez
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：June 11, 2015
• 年：2015
• 卷：58
• 期：11
• 页码：4851-4856
• 全文大小：289K
• ISSN：1520-4804

文摘

The TOP2 poison etoposide has been implicated in the generation of secondary malignancies during cancer treatment. Structural similarities between TOP2 isoforms challenge the rational design of isoform-specific poisons to further delineate these processes. Herein, we describe the synthesis and biological evaluation of a focused library of etoposide analogues, with the identification of two novel small molecules exhibiting TOP2B-dependent toxicity. Our findings pave the way toward studying isoform-specific cellular processes by means of small molecule intervention.