Efficiency of hit generation and structural characterization in fragment-based ligand discovery

Fragment-based ligand discovery constitutes a useful strategy for the generation of high affinity ligands with suitable physico-chemical properties to serve as drug leads. There is an increasing number of generic biophysical screening strategies established with the potential for accelerating the generation of useful fragment hits. Crystal structures of these hits can subsequently be used as starting points for fragment evolution to high affinity ligands. Emerging understanding of the efficiency and operative aspects of hit generation and structural characterization in FBLD suggests that this method should be well suited for academic ligand development of chemical tools and experimental therapeutics.

► FBLD is a resource efficient strategy to generate ligands.
► Good structural information is essential for FBLD.
► The toolbox for biophysical screening of fragments is rapidly growing.
► FBLD is gaining interest as a tool for screening for chemical probes in academia.