Lead Discovery

Once a biological target has been identified the search for a chemical lead begins.  Potential sources may start with an understanding of the underlying physiology and the hormones that trigger a particular pathway.  Alternatively biophysical methods, such as X-ray crystallography and NMR, can provide 3D models of proteins that can be used to design new compounds that might bind to the target.  Virtual screening techniques have been developed to predict ways in which libraries of compounds might interact with proteins and prioritise the order in which they should be tested.  These fall into two categories: methods where a small molecule is docked into a specific site on a protein; and those where compounds are selected on the basis of their similarity to the physical properties of a known ligand.  Some early success suggests that these methods can give 10-100 fold improvements in finding initial hits over simple high throughput screening strategies. The DDC has facilities for creating molecular models to help find initial hits.

A certain amount of chemical synthesis is required to develop bioassay tools, although the first hits identified may well be commercially available compounds or existing drugs.  The DDC can help with synthesis of compounds required for this stage, as well as optimising early stage hits into leads.