Abstract

Current Perspectives in Fragment Based Lead Discovery

Roderick Hubbard, Senior Fellow & Professor, Vernalis R&D Ltd

Fragment-Based Lead Discovery (FBLD) is now maturing as an approach to hit identification, with many compounds now in clinical trials and the first compound on the market.   The central feature is that the drug discovery process begins with identification (usually by biophysical methods) of small (<250 MW), weakly binding (affinity of 100s of µM) compounds which are then optimised to drug candidates by structure-guided design.  The advantages are that a small library can sample a potentially large chemical diversity to generate novel lead compounds and that hits can be identified for new classes of target for which existing compound collections cannot provide a hit.
I will discuss recent developments in the methods and their application with a focus on fragment to hit evolution. This includes such issues as deciding which fragments to progress; combining fragments with HTS and literature data; and how to work with challenging targets, such as protein-protein interactions.