The Cover

Discodermolide is a potent microtubule stabilizer whose actions are not affected by cells with mutations in the paclitaxel binding site. Such resistant human ovarian carcinoma cells (PTX10) treated with 62.5 nM discodermolide are shown in this multiparameter fluorescence image, which includes the drug-stabilized microtubule cytoskeleton (green), cellular nuclei (yellow), and the phosphorylated forms of histone H3 (red) and the stress kinase target RSK90 (blue). Defining the heterogeneous response of populations of living cells is made possible with high content profiling, an automated image analysis platform for drug discovery. For details on how this system was used to evaluate simplified synthetic analogs of discodermolide, see 1305 in this issue.