This presentation will discuss the structure based drug design and the optimization of two lead series of PLK1 inhibitors.  This work led to the discovery of TAK-960, an orally available and selective PLK1 inhibitor currently in a Phase I clinical trial in patients with advanced non-hematologic malignances. PLK1 inhibition is an attractive approach for the treatment of proliferative diseases, for PLK1 plays a key role in the regulation of mitotic progression and the over-expression of PLK1 is associated with poor prognosis and survival rates in a number of human cancers. The discovery of TAK-960 highlights how the incorporation of fluorine atoms during optimization can be used to address MDR-1 efflux deficiencies of a lead series.

Structure based drug design and optimization of inhibitors of Polo-like Kinase 1 (PLK1)

244th National Meeting (2012)

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