To study the effect of cellular context on perturbational responses, we compared the signatures of 2,429 drugs across 9 cancer cell lines. On average, 38% of compounds scored as transcriptionally active in any single cell type (range 28%-45%) and 92% of small molecule drugs scored as active in at least one cell line. Of 1,399 (58%) compounds active in at least 3 cell lines, 26% (corresponding to 15% of all compounds) produced highly similar signatures across the entire panel, whereas the remainder were active in only 1 or 2 cell lines or produced a diversity of cellular signatures (see STAR Methods and Figure S2B, S2C).