Figure 5 from Screening FDA-Approved Oncology Drugs with Three-Dimensional Spheroids Identifies Romidepsin as a Therapeutic Candidate for Osteosarcoma

<p>Romidepsin is more promising than all other tested HDIs. Romidepsin was compared with the three other FDA-approved HDIs, as well as eight that are in clinical trials. Five of the HDIs in clinical trials (abexinostat, givinostat, mocetinostat, pracinostat, and quisinostat) weakly inhibited sarcosphere metabolic activity when tested at their Cmax in preliminary studies and were therefore excluded from further study (Supplementary Fig. S7). All heatmaps in this figure are sorted by the overall row means shown in the first column of each heat map. Dark blue indicates highest values (most favorable), dark red the lowest values (least favorable), and white is set at the median of the row means. <b>A</b> and <b>B,</b> Ratios of Cmax/sarcosphere (Sarco) ED<sub>50</sub> with and without MAP reflect potency at clinically achievable concentrations. Cmax and dose responses are shown in Supplementary Table S3 and Supplementary Fig. S8. ED<sub>50</sub>s were determined for sarcospheres derived from LM7, 143B, and MG63.3-GFP cell lines in <i>N</i> = 3 independent dose–response experiments with each drug. Each experiment included three sarcospheres per group. <b>C,</b> Ratios of TD<sub>50</sub>/sarcosphere (Sarco) ED<sub>50</sub> reflect therapeutic indices with NHOst. TD<sub>50</sub>s were determined in <i>N</i> = 3 independent dose–response experiments with each drug. Each experiment included at least three culture wells per group.</p>