Searching the Enamine REAL Space -Some structures from Schmidt et al. To illustrate the performance of our substructure search algorithm for searches in the Enamine REAL Space we consider structures that were mentioned in a recent publication on computing the IMCS in combinatorial spaces. The Enamine REAL space is the only commercial space, for which we have access to a synthon representation, therefore we cannot state any results for the WuXi AppTec GalaXi 12 or OTAVA CHEMriya 13 spaces. It is difficult to directly compare runtimes for our and their method for two reasons: (i) their method in general solves a much harder problem, and (ii) their method only works under the strong restriction that ring / non-ring edges are exclusively matched to similar edges. Regarding (ii), it is important to stress that our method comes without any restrictions except for that the query substructure must be connected and that it returns the exact solution to the given substructure search problem and not in any way an approximation.