RG7388 is representative of an entirely new branch of the nutlin family of MDM2 antagonists and the second agent with this mechanism of action sponsored by Roche. As with the lead compound (RO5045337), RG7388 binds selectively to the p53 site on the surface of the MDM2 molecule in vitro with high affinity and can effectively displace p53 from MDM2, leading to stabilization and accumulation of p53 protein and activation of the p53 pathway. RG7388 is from a different chemical series compared to the lead compound and binds with higher potency and selectivity to the MDM2 protein. This follow-on compound has substantially improved pharmacological properties. Preclinical models predict superior efficacy of RG7388 in the clinic at lower doses and exposures. Compared to the lead molecule, lower variability may be seen given that RG7388 does not have significant pH dependent solubility (fasted and fed-state simulated intestinal fluid solubilities are similar). RG7388 at 0.3 μM has equivalent apoptotic activity to RO5045337 at 10-fold higher (3 μM) concentration and at 25 mg/kg has equivalent efficacy to RO5045337 at 4-fold higher dose (100 mg/kg) and better potency when given once weekly.