In vitro activity: HDM201 acts by binding to the p53 binding-site of the Mdm2 protein, thereby disrupting the interaction of the two proteins (p53 and Mdm2) and leading to the activation of the p53 pathway. It induces robust p53-dependent cell cycle arrest and apoptosis in human p53 wild-type tumor cells. HDM201 exhibits highly selectivity across a panel of cancer cell lines

Cell Assay: The in vitro combination screen was performed at Horizon Discovery (Cambridge, MA) on cancer cell lines, and data analysis was performed as described previously. Here we focused the data analysis on combinations with CGM097, a previous class of selective TP53-MDM2 inhibitors. A total of 485 cancer cell lines were treated with varying concentrations of CGM097 and for 25 other compounds. We integrated the information on TP53 mutation status and differentiated cell lines with no TP53 mutation from cell lines with TP53 alteration. We assessed the synergistic effect of combinations of HDM201and A-1155463 as described previously.