Fragment-based lead discovery against the protein-protein interaction between Aurora A and TPX2 for the treatment of cancer (360G-Wellcome-101134_Z_13_A)

The Wellcome Trust has awarded over £2.3 million to Chris Abell, John Skidmore and co-workers at the University of Cambridge to use fragment-based approaches for the generation of molecules which disrupt the interaction between the kinase Aurora A and the regulatory protein TPX2. Such compounds are expected to have utility in the treatment of a number of solid and haematological cancers, with one particular focus being reversal of taxane resistance in solid tumours. The project will generate lead compounds suitable for screening in cancer cell-lines and animal models to further validate the target and will also provide leads for future optimisation towards a drug. This funding follows on directly from an ongoing Strategic Award pioneering the use of fragment-based approaches against protein-protein interactions, which used biophysical screening and X-ray crystallography to generate the fragment leads for the planned project.