Targeted Protein Degradation Using Small Molecules

Recent work from the Giamas group has concentrated on the discovery and mechanism of action of Lemur Tyrosine Kinase 3 (LMTK3). The latter is implicated in resistance to endocrine cancer therapies including tamoxifen, by phosphorylation of the ER protein (http://www.sussex.ac.uk/lifesci/giamaslab/). A recent, unpublished, collaboration with the Spencer group (http://www.sussex.ac.uk/lifesci/spencerlab/) has led to the discovery of selective, nM potent LMTK3 inhibitors. This iCASE project, funded by GlaxoSmithKline (GSK) and EPSRC, and involving a 3-month placement at GSK, Stevenage, will be based at Sussex and will look to produce PROTACs (proteolysis targeting chimeras) to selectively target LMTK3 and destroy it via the proteasome. Further studies will explore novel modalities of inducing protein degradation