Fragment-based discovery identifies low molecular weight molecules which make key interactions with their target binding site. Fragments provide a range of efficient starting points from which potent ligands, and eventually drugs, can be developed.
Over the past decade we've developed our proprietary library of fragments, successfully applied to more than 20 targets. Our library is screened experimentally, typically using NMR spectroscopy, with the structure of bound fragments determined by X-ray crystallography or, if required, NMR.
By combining structural, thermodynamic and kinetic information from the wide range of ligand hits, we are able to design novel potent drug-like molecules.
Fragment to development candidate: 6 months
- Hsp90 - phase II candidate and oral backup
- Fragment to lead; rapid structure-based optimisation
- Chk1 - pre-clinical candidate
- Fragment growth
- PDPK1 - tool compound to probe biology
- Merging fragments with literature compounds
- Bcl-2 - protein-protein interaction - phase I clinical candidate
- Mcl-1 - protein-protein interaction - phase I clinical candidate
- NMR to generate models of ligand binding; biophysics to characterise compound properties
- FAAH - completed phase 1
- Modelling to rapidly generate candidate
- Tankyrase - tool compound to probe biology
- Fragment hits from X-ray; off-rate screening
- PDHK1 - off-rate screening to identify selective lead