Author/Authors :
Kiranmai Gumireddy، نويسنده , , Kiranmai and Reddy، نويسنده , , M.V. Ramana and Cosenza، نويسنده , , Stephen C. and Nathan، نويسنده , , R. Boomi and Baker، نويسنده , , Stacey J. and Papathi، نويسنده , , Nabisa and Jiang، نويسنده , , Jiandong and Holland، نويسنده , , James and Reddy، نويسنده , , E. Premkumar Reddy، نويسنده ,
Abstract :
Summary
ed 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.
