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

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.