The c-MYC/MAX transcription factor mediates a number of important cellular functions; most notably those related to proliferation and differentiation. c-MYC upregulation has been implicated in a number of cancers and is correlated with a poorer prognosis and median survival. However, despite the clear importance of c-MYC/MAX in the progression of carcinogenesis, no inhibitors of c MYC/MAX activity have yet reached clinical application. In this thesis, attempts to use the well characterised couple of reverse two hybrid system and split-intein circular ligation of peptides and proteins (RTHS/SICLOPPS) were used to attempt to find novel cyclic peptide inhibitors of this interaction. With the failure of the standard methodology to provide any lead compounds from several screens and libraries, new techniques were developed. The ultimate development of this approach was the addition of next generation sequencing to attempts to identify protein-protein interaction inhibitors; however, even this approach did not yield lead compounds for the c-MYC/MAX RTHS. However, this work showed some systems are resistant to standard SICLOPPS screening without specific adaptations (specially designed libraries, for instance). In addition, the new SICLOPPS/RTHS/NGS workflow improves screening significantly by; providing early hints of structure-activity information before bioassay; allowing full characterisation of peptides with good RTHS disruption; and minimising screening noise from mutant cells escaping RTHS control.