A high-content, cell-based screen identifies micropolyin, a new inhibitor of microtubule dynamics

Manu De Rycker, Laurent Rigoreau, Sarah Dowding, Peter J. Parker

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

High-content cell-based screens provide a powerful tool to identify new chemicals that interfere with complex biological processes. Here, we describe the identification of a new inhibitor of microtubule dynamics (micropolyin) using a high-content screen. Integrated high-resolution imaging allowed for fast selection of hits and progression to target identification. Treatment of cells with micropolyin efficiently causes a pro-metaphase arrest, with abnormal spindle morphology and with the spindle assembly checkpoint activated. The arrest appears to result from interference of micropolyin with microtubule dynamics. We show in vitro that tubulin is indeed the target of micropolyin and that micropolyin inhibits microtubule polymerization. Our results demonstrate the power of high-content image- and cell-based screening approaches to identify potential new drug candidates. As our approach is unbiased, it should allow for discovery of new targets that may otherwise be overlooked.

Original languageEnglish
Pages (from-to)599-610
Number of pages12
JournalChemical Biology and Drug Design
Volume73
Issue number6
DOIs
Publication statusPublished - Jun 2009

Keywords

  • Cell cycle
  • Chemical genetics
  • High-content screen
  • Inhibitors
  • Microtubule

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