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Differential Targeting of Human Topoisomerase II Isoforms with Small Molecules

Lookup NU author(s): Angelica Mariani, Dr Mandeep Atwal, Ka Lee, Emerita Professor Caroline AustinORCiD

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Abstract

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.

Publication metadata

Author(s): Mariani A, Bartoli A, Atwal M, Lee KC, Austin CA, Rodriguez R

Publication type: Article

Publication status: Published

Journal: Journal of Medicinal Chemistry

Year: 2015

Volume: 58

Issue: 11

Pages: 4851-4856

Print publication date: 11/06/2015

Online publication date: 06/05/2015

ISSN (print): 0022-2623

ISSN (electronic): 1520-4804

Publisher: American Chemical Society

URL: http://dx.doi.org/10.1021/acs.jmedchem.5b00473

DOI: 10.1021/acs.jmedchem.5b00473

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