Abstract

Using Fragments To Activate, Inhibit And Probe

Roderick Hubbard, Professor, University of York

It is now over 20 years since the first fragment based discovery projects were disclosed. The techniques are now mature for most “conventional” targets, identifying tractable chemical startpoints that non-covalently inhibit an enzyme activity – and a large number of fragment derived compounds are now in clinical trials and two are on the market. There has also been growing success on more challenging targets, such as protein-protein interactions. In this presentation, I will briefly illustrate the currently adopted paradigm with examples from successful drug discovery projects. I will then discuss applications of fragment methods to chemical biology projects: (1) identifying and then tethering fragments to activate enzyme activity, (2) the initial results from a semi-phenotypic screen of the bacterial replisome to identify potential strategies for antibiotic discovery and (3) use of fragments to explore binding sites.