Novel molecular strategies for targeting Pin1 to treat cancer

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Developing new drugs to treat cancer is a high priority in clinical and pharmaceutical research. For many cancers there are no effective drugs, or existing drugs have severe side-effects which negatively impact on patient wellbeing. Therefore, there is an urgent need for the development of new medicines that work in smarter ways. This project will develop cutting-edge pharmaceuticals that target an important communication hub protein called Pin1. Pin1 is a prolyl isomerase protein that is heavily implicated in many cancer types and inhibiting its activity has been shown to be an effective therapeutic strategy. A handful of Pin1 small molecule inhibitors have been reported, but so far none have made a significant impact. This is largely due to problems associated with poor potency and selectivity. Furthermore, the molecular basis for Pin1 function is poorly understood which hampers its maturation as a drug target. This project will address these issues by investigating recently discovered cooperative dual ligand inhibition of Pin1, allosteric ligand binding effects, and consequences of Pin1 phosphorylation.