Targeting protein-protein interactions for therapeutic intervention: a challenge for the future

Over the last two decades, an increasing research effort in academia and industry has focused on the modulation (both inhibition and stabilization) of protein-protein interactions (PPIs) in order to develop novel therapeutic approaches and target-selective agents in drug discovery.

The diversity and complexity of highly dynamic systems such as PPIs present many challenges for the identification of drug-like molecules with the ability to modulate the PPI with the necessary selectivity and potency. In this review, a number of these strategies will be presented along with a critical overview of the challenges and potential solutions relating to the exploitation of PPIs as molecular targets.

Both traditional drug discovery approaches and some more recently developed innovative strategies have already provided valuable tools for the discovery of PPI modulators, and a number of successful examples have highlighted the potential of targeting PPIs for therapeutic intervention, especially in the oncology area.