(Figure ). Hundreds to thousands (Median 841) of these SPMs are available for each fragment. Considering the larger leadlike chemical space, derivatives which are substituted in more than one position and with larger substituents, tens to hundreds of thousands (Median 76 532) of possible follow-up compounds become accessible, thus allowing for rapid expansion of binding fragments (Figure ). In addition, for each fragment a multitude of similar fragments are available in each underlying cluster. This means that besides the multitude of substituted derivatives, there are at least ten different scaffold variations (Median 18) available for each, similar in 3D-shape and arrangement of chemical features (Figure ). This allows rapid scaffold hopping and thereby aids the easy and quick development of putative hits further and contributes to the already tremendous sociability of these fragments.