A high-content, cell-based screen identifies micropolyin, a new inhibitor of microtubule dynamics.
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.
De Rycker
Manu
M
Protein Phosphorylation Laboratory, London Research Institute, Cancer Research UK, London, UK.
Rigoreau
Laurent
L
Dowding
Sarah
S
Parker
Peter J
PJ
D000465:Algorithms; D000813:Anilides / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003078:Colchicine / Q000378:metabolism; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D049468:Prometaphase; D054852:Small Molecule Libraries; D012984:Software; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000737:chemistry / Q000494:pharmacology*
D000813:Anilides; D054852:Small Molecule Libraries; D014404:Tubulin; D050257:Tubulin Modulators; D003078:Colchicine