2. Academic Validation
  3. Differential Targeting of Human Topoisomerase II Isoforms with Small Molecules

Differential Targeting of Human Topoisomerase II Isoforms with Small Molecules

  • J Med Chem. 2015 Jun 11;58(11):4851-6. doi: 10.1021/acs.jmedchem.5b00473.
Angelica Mariani 1,  Alexandra Bartoli 1,  Mandeep Atwal 2,  Ka C Lee 2,  Caroline A Austin 2,  Raphaël Rodriguez 1 3
Affiliations

Affiliations

  • 1 †Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles du CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
  • 2 ‡Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom.
  • 3 §Organic Synthesis and Cell Biology Group, Institut Curie Research Center, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
PMID: 25945730 DOI: 10.1021/acs.jmedchem.5b00473
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.

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