Science. 1999 Oct 29;286(5441):971-4.

Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen.

Mayer TU, Kapoor TM, Haggarty SJ, King RW, Schreiber SL, Mitchison TJ.

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Department of Cell Biology, and Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Thomas_Mayer@hms.harvard.edu

Abstract

Small molecules that perturb specific protein functions are valuable tools for dissecting complex processes in mammalian cells. A combination of two phenotype-based screens, one based on a specific posttranslational modification, the other visualizing microtubules and chromatin, was used to identify compounds that affect mitosis. One compound, here named monastrol, arrested mammalian cells in mitosis with monopolar spindles. In vitro, monastrol specifically inhibited the motility of the mitotic kinesin Eg5, a motor protein required for spindle bipolarity. All previously known small molecules that specifically affect the mitotic machinery target tubulin. Monastrol will therefore be a particularly useful tool for studying mitotic mechanisms.

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Science. 1999 Oct 29;286(5441):913-4.

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