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

Kiranmai Gumireddy, M. V.Ramana Reddy, Stephen C. Cosenza, R. Boomi Nathan, Stacey J. Baker, Nabisa Papathi, Jiandong Jiang, James Holland, E. Premkumar Reddy

Research output: Contribution to journalArticlepeer-review

334 Scopus citations

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.

Original languageEnglish
Pages (from-to)275-286
Number of pages12
JournalCancer Cell
Volume7
Issue number3
DOIs
StatePublished - Mar 2005

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