High Affinity Non-Peptidic Small Molecule Inhibitors of MDM2-p53 - Interaction through Virtual Screening Strategies

Since the discovery of p53 in 1979 (Lane et al., 1979; DeLeo et al., 1979; Linzer et al., 1979); it has surfaced as a most important tumor suppressor protein central to regulation of cell cycle, apoptosis, DNA repair, senescence, and angiogenesis (Vousden et al., 2002; Fridman et al., 2003; Teodor et al., 2007). The prominent role of p53 is reflected in nearly 50% cases of malignancies wherein p53 gene is either mutated or under expressed (Feki et al., 2004, Srivatanakul et al., 2004; Xu et al., 2012, Tian et al., 2013). However, the pioneering studies by Oliner et al. (1992) provided a convincing evidence of involvement of other regulatory proteins that encourages abnormal cell division. Involvement of MDM2 (Murine Double Minute 2) as an ancillary protein in sarcomas (Oliner et al., 1992, Yang et al., 2014) provided a fresh