Drug Discovery Opinion

Polo-like kinase 1 (Plk1) has received attention in recent years as a potential target for intervention in cancer. It is known to be important in regulation of cell cycle progression during M-phase and has been shown to be overexpressed in certain tumours. Now scientists at the NYU Cancer Institute and Howard Hughes Medical Institute have shown that Plk1 is involved in a new pathway associated with the cellular response to DNA damage. In the July 25th issue of Cell, the authors describe targeting of the phosphatase Cdc14B to APC/C, a protein that marks other proteins for destruction. The resultant activated APC/C then tags Plk1 for destruction. If Plk1 remains active, the cell continues to divide despite the DNA damage.

Tekmira Pharmaceuticals, a specialist in delivery of RNA interference molecules, has just announced plans to advance an siRNA product targeting Plk1 into Phase 1 clinical trials in the second half of 2009. Meanwhile, the search for small molecule inhibitors of Plk1 continues. Scientists at Pfizer deposited x-ray coordinates of the catalytic domain of a mutant Plk1(complexed with BI2536) in the protein data bank earlier this year. Additional structure factors have been deposited by Sunesis scientists, although the coordinates have not yet been released.