1. Academic Validation
  2. Wortmannin, a widely used phosphoinositide 3-kinase inhibitor, also potently inhibits mammalian polo-like kinase

Wortmannin, a widely used phosphoinositide 3-kinase inhibitor, also potently inhibits mammalian polo-like kinase

  • Chem Biol. 2005 Jan;12(1):99-107. doi: 10.1016/j.chembiol.2004.11.009.
Yongsheng Liu 1 Kevin R Shreder Wenzhi Gai Sergio Corral Douglas K Ferris Jonathan S Rosenblum
Affiliations

Affiliation

  • 1 ActivX Biosciences, Inc., 11025 North Torrey Pines Road, La Jolla, CA 92037, USA. yongshengl@activx.com
Abstract

Polo-like kinases (PLKs) play critical roles throughout mitosis. Here, we report that wortmannin, which was previously thought to be a highly selective inhibitor of phosphoinositide (PI) 3-kinases, is a potent inhibitor of mammalian PLK1. Observation of the wortmannin-PLK1 interaction was enabled by a tetramethylrhodamine-wortmannin conjugate (AX7503) that permits rapid detection of PLK1 activity and expression in complex proteomes. Importantly, we show that wortmannin inhibits PLK1 activity in an in vitro kinase assay with an IC(50) of 24 nM and when incubated with intact cells. Taken together, our results indicate that, at the concentrations of wortmannin commonly used to inhibit PI 3-kinases, PLK1 is also significantly inhibited.

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