Fragment libraries must not only represent the available chemical space evenly in terms of structure but also in terms of properties. There is a shift towards smaller and more RO3compliant fragments for the Core and General libraries. For the Core library, most of the fragments (73%) have a heavy atom count (HAC) between 11-15 and 80% of these fragments have a molecular weight between 140 and 220 Da, thus focusing on the smaller compounds from the in-stock library (Figure A & B). This allows for plenty of room for subsequent optimisation and limits complexity and, possibly, the risk of unfavourable interactions. Threequarters of the fragments possess one or two hydrogen-bond acceptors, allowing for the formation of strong binding interactions without creating too much complexity (Figure ).