Targeting the c-MYC oncoprotein with stapled-peptides for cancer therapeutics

The oncoprotein c-MYC is a well-established target for anti-cancer therapeutics.

However, it has been extremely challenging to develop a clinically viable drug against c-MYC because it is a nuclear transcription factor and an intrinsically disordered protein devoid of any stable structural fold with druggable pockets. This presents a major obstacle in the discovery of drugs through conventional methods.

We will therefore embark on an integrative research program towards developing innovative therapeutic molecules against c-MYC such as stapled-peptides.

These are a novel class of bioactive alpha helical compounds that are developed to specifically target and modulate protein-protein interactions (PPIs).

Despite their immense promise, the generally poor cell membrane permeability of these peptides has limited their potential therapeutic utility against intracellular PPIs which are prime targets for drug development.

This research work will therefore aim to establish new strategic pipeline to design, develop and efficiently deliver stapled-peptides into cells to inhibit the activity of c-MYC in vitro and in vivo.

A successful outcome will offer promising lead compounds to target c-MYC for clinical use and serve as a generic modality to expand the druggable target space of stapled-peptides as intracellular PPI inhibitors.