The aim of this project is to combine molecular modeling with state-of-the-art medicinal chemistry methods to design and synthesise novel, selective, low molecular weight, substrate-like inhibitors of the MET tyrosine kinase. The Nottingham group is involved in the discovery of new agents that target cell-signaling pathways in order to develop rational chemotherapeutic strategies. Receptor protein kinases have been identified as potential new targets for drug design because of their involvement in cell signaling.
MET kinase is of particular interest, as it does not appear to be expressed in normal tissue thus minimizing the risks of a long-term kinase blockade strategy. To date most strategies aimed at receptor tyrosine kinases have involved blocking the ATP binding site and rely on exploiting differences between relatively well- conserved binding pockets to attain selectivity. The approach that will be taken here is different in that it is the substrate binding sites that will be targeted.
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