Quantitative chemical proteomics reveals a Plkl inhibitor-compromised cell death pathway in human cells

Dear Editor, Because multiple cancers require Polo-like kinase （Plk） 1 for survival [1-3], Plkl has been investigated intensively as a target for novel anti-cancer agents [4- 6]. Although many small molecule Plkl inhibitors have reached the clinic, our knowledge about their target profiles is limited, because their biochemical properties are determined mostly using in vitro kinase assays. It remains unclear whether this approach reflects the true pharmacodynamic properties of Plkl 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 Plkl inhibitor BI2536, we treated HeLa cells with serial dilutions of this inhibitor.