Fragment-Based Drug Discovery implies usage of small, not very selective compounds – fragments. The compounds are selected by the “Rule of 3” cutoff, so that it would be possible to combine fragment hits to form a drug-like compound.
This solution, in summary, allows sampling the chemical space without using exhaustive screens with large in-stock collections. Moreover, as the fragment-like compounds are not so specific while binding to the protein, FBDD enables discovery of the unknown binding sites on the protein (the “hot spots”).
Recently, an approach that goes further into this area was published*: use even smaller compounds to identify the “hot” and “warm” spots on the surface. Usage of the information on these sites, especially the “warm” ones (that are not easily identified through traditional and fragment screens) leads to better understanding the active site binding and improve large ligand affinity.
Discover Chemspace Tiny Fragments – a library of PAINS- and undesirable reactivity-free compounds that have 5-8 heavy atoms. For make-on-demand set, please contact us at firstname.lastname@example.org.
*O’Reilly, M. et al., Drug Discovery Today (2019)