RG7112, the first MDM2 inhibitor to progress into Phase 1 clinical trials, is a structurally modified analogue of Nutlin-3 with improved MDM2 affinity (IC50 ~18 nM), increased potency (Kd ~11 nM) and enhanced selectivity with a 14-fold higher affinity for mutant compared with wt p53 [124,132,133] Preclinical evaluation of RG7112 in glioblastomas and osteosarcoma models demonstrates its effectiveness in triggering tumor cell apoptosis and reducing tumor volume, specifically in MDM2-overexpressing tumors with wt p53 [132,134]. The gene discussed is TP53; the disease is osteosarcoma.