Fragmentbased
Fragment-based (often referred to as fragment-based drug discovery or FBDD) is a strategy in medicinal chemistry in which small, low-molecular-weight chemical fragments are screened for binding to a biological target. These fragments, typically with molecular weight under 300 Da and high ligand efficiency, bind with weak affinity but offer efficient coverage of chemical space. Hits are then elaborated through structure-guided optimization to produce higher-affinity, drug-like compounds.
Fragment libraries are designed to maximize structural diversity and include diverse heteroatoms; screening methods include biophysical
Optimization strategies include fragment growing (adding atoms to increase affinity), fragment merging (combining two bound fragments),
Advantages include efficient exploration of chemical space with smaller libraries, higher hit rates per molecule, and
Fragment-based approaches have contributed to numerous drug discovery programs across targets such as kinases and proteases