Targeting Taspase1 for Cancer Therapy—Letter Available to Purchase

We read with interest the article by Chen and colleagues (1), identifying a potential Taspase1 inhibitor by using a cellular translocation assay similar to the one described by Bier and colleagues (2). These results impressively underline the power of cell-based screening, as previous attempts to identify effective small-molecule Taspase1 inhibitors by in silico or in vitro assays failed. However, one is wondering why screening was conducted in HEK293T cells, which do not express measurable levels of Taspase1 (3). Also, the results of the Ala-scan mutagenesis question the previously published Taspase1 consensus motif (2). The authors claim the critical importance of isoleucine at position P5, although the Taspase1 target USF2 contains an aspartate at P5 (2). Collectively, these factors might have contributed to the fact that only one chemical inhibitor, NSC48300, was identified, showing Taspase1 specificity in in vitro assays. Albeit...