Fsp3, FCstereo, nSPS were calculated for comparison for all compounds from the different data sets (Figure ). Interestingly, we observed that a high proportion of the DCM compound collection shows relatively low nSPS with a median score of 14.3. DrugBank gave a relatively high overlap with DCM with the median score of 14.4, however, its distribution also showed a very long tail with the maximum nSPS values reaching 66.4. Compounds from the Enamine collection had higher median nSPS than DCM and DrugBank molecules and was equal to 18.2. There is a general chemical intuition that NPs produced via biosynthetic cascades are typically more complex than synthetic molecules produced via chemical reactions. In line with this intuition, ChEMBL NPs have the highest nSPS median value (28.0) and a relatively broad distribution (maximum nSPS of 76.0) relative to the other reference sets. The wide range of nSPS values for NPs expresses their rich structural diversity, which includes such simple molecules like salicylic-and cinnamic acid but also extends to more intricate compounds such as morphine or strychnine. Despite its more structurally-holistic approach, nSPS still conserves the characteristic distinction between the distributions of synthetic compounds and NPs as it is seen for FCstereo. An analogous analysis employing size-normalised Cm scores could not differentiate the reference compound sets (Figure ). The relatively high FCstereo and Fsp3 of NPs may explain the significant correlation of nSPS to the NP-likeness score.