ON01910, a non-ATP-competitive small molecule inhibitor of Plk1, is a potent anticancer agent

  • Cancer Cell. 2005 Mar;7(3):275-86. doi: 10.1016/j.ccr.2005.02.009.
Kiranmai Gumireddy  1 ,  M V Ramana Reddy ,  Stephen C Cosenza ,  R Boominathan ,  Stacey J Baker ,  Nabisa Papathi ,  Jiandong Jiang ,  James Holland ,  E Premkumar Reddy
Affiliations
  • 1. Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 N. Broad Street, Philadelphia, Pennsylvania 19140, USA.
PMID: 15766665 DOI: 10.1016/j.ccr.2005.02.009
Abstract

Elevated expression of polo-like kinase1 (PLK1) has been reported in many human tumors, and inhibition of PLK1 activity results in their mitotic arrest and Apoptosis. Here we describe the profile of ON01910, a small molecule inhibitor of PLK1 activity, which induces mitotic arrest of tumor cells characterized by spindle abnormalities leading to their Apoptosis. This compound was not ATP-competitive, but competed for the substrate binding site of the enzyme. In vivo, this compound did not exhibit hematotoxicity, liver damage, or neurotoxicity, and was a potent inhibitor of tumor growth in a variety of xenograft nude mouse models. ON01910 showed strong synergy with several chemotherapeutic agents, often inducing complete regression of tumors.

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