Reactivation of p53 via MDM2 inhibition.

Abstract

At diagnosis, 498% of neuroblastoma are p53 wild-type with intact downstream apoptotic machinery.[1]
Initial efforts to optimize the Nutlin compounds led to the first investigational MDM2 inhibitor, RG7112.6 Preclinical evaluation of RG7112 demonstrated robust activation of the p53 pathway with a potent antitumor effect in vitro and in vivo.[8,9]
Hai et al tested the efficacy of RG7388 in several cell lines of non-small cell lung cancer.[12]. They confirmed that RG7388 led to p53-dependent apoptosis of cancer cells, and in vivo, RG7388 significantly inhibited subcutaneous tumor xenografts from p53 wild-type cells but not tumors derived from p53 mutant cells