Identification and Optimisation of Inhibitors of the Aurora A/N-Myc Protein-Protein Interaction in Neuroblastoma

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The project will focus on identifying compounds which can disrupt the Aurora A/N-Myc protein-protein interaction. The N-Myc protein is often overexpressed in the paediatric tumour Neuroblastoma and correlates with a poorer prognosis. N-Myc is highly variable and is considered "undruggable". However the Aurora A/N-Myc complex contains sites which could be targeted by small molecules and disrupt the interaction. When N-Myc is removed from this complex, sites of phosphorylation become accessible, which targets the protein for proteasomal degradation. Reduction of N-Myc leads to cell death and shows promise as a therapy for some cancers.The project will involve virtual screening to identify initial hits from fragment and compound libraries, biological assays to assess binding strength and synthesis of analogues to optimise hits.