An early example of a class A mimetic involves a modified octapeptide comprising four non-natural amino acids that binds HDM2 in vitro with nanomolar affinities.[357–359] This peptide mediates the accumulation of p53 in cancer cells, thereby promoting cell death by apoptosis.[360] Again, low cellular uptake and low proteolytic resistance are the main drawbacks of this peptide. Here, TP53 is linked to cancer.