Identification and development of compounds targeting childhood brain cancer

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Our collaborators have identified a protein called ATIC, an enzyme that catalyses that last two steps of the de novo purine biosynthesis pathway, as being important for the survival of a subset of childhood brain tumours. Their experiments with a small molecule ATIC inhibitor developed by our lab has shown that these tumour cell lines are sensitive to ATIC inhibition, significantly increasing the survival rate in pre-clinical mouse models. In this project, we will develop next-generation inhibitors of ATIC with improved in vitro and cell-based activity. This will involve synthesis and testing of analogues of our ATIC inhibiotr. In addition to the medicinal chemistry core of this project, the project will proivide training in a variety of chemical biology teniques such as recombinant protein-expression and purificaiton, and biochemical and cell-based assays.