LETTER TO THE EDITOR Quantitative chemical proteomics reveals a Plk1

Because multiple cancers require Polo-like kinase (Plk) 1 for survival [1-3], Plk1 has been investigated intensively as a target for novel anti-cancer agents [4-6]. Although many small molecule Plk1 inhibitors have reached the clinic, our knowledge about their target pro-files is limited, because their biochemical properties are determined mostly using in vitro kinase assays. It remains unclear whether this approach reflects the true pharmaco-dynamic properties of Plk1 inhibitors, since these assays often address only small portions of the human kinome and typically use a recombinant kinase and an artificial substrate. In the present study, for a more comprehensive characterization of the clinical Plk1 inhibitor BI2536, we treated HeLa cells with serial dilutions of this inhibitor. At rising concentrations of up to 100 nM BI2536, we observed a significant mitotic arrest, a high percentage of rounded cells and increasing levels of cell death (Figure 1A and Supplementary information, Figure S1A). Above this drug concentration, the apoptotic activity did not fur-ther increase significantly or decreased to a small exten