MDM2 and cancer: Even though this molecule has only one polar interaction, the increased volume of the substituents that enhance the interactions in the key binding pockets is sufficient to achieve potent binding to MDM2 of IC50 = 0.65 nM, cell activity of IC50 = 122 nM in wt-p53 HCT116 cancer cells, and robust antitumor activity in vivo in an SJSA-1 xenograft model (Table 1).