Compounds were further assigned into three complexity levels, depending on the considered scoring system. Based on Fsp3 index, molecules were classified using score thresholds of 0.3 and 0.6, and based on FCstereo, using thresholds of 0.0 and 0.25. The selected FCstereo classification values also matched the categorisation values used previously by Clemons et al. Compounds were assumed to have low nSPS when the score was below 11.2 (25 th percentile of the analysed ChEMBL compounds) or high nSPS with the value above 17.7 (75 th percentile). The analysis revealed that molecules with medium or high Fsp3 (above 0.3) tend to have higher activity in assays than compounds with high unsaturation (Figure ). We also observed that structures with medium values of FCstereo have the highest proportion of the high compound activity (54%) compared to compounds with either no stereogenic carbons or compounds with high values of FCstereo (Figure ). The differences in activity between molecule bins, with low, medium and high nSPS values are highly conspicuous. Low nSPS is associated with a high proportion of low activity compounds (39%) and a low proportion of highly active compounds (28%). The proportion of highly active structures increases for the molecules with medium nSPS (45%) and reaches a majority (55%) for structures with high nSPS. Compounds with a high nSPS also have a low proportion of structures with low activity in assays (23%; Figure ). Further data analysis of relationship between activity and nSPS revealed that on average the highest activity is achieved by compounds with nSPS values between ca. 20 and 40 (Figure ). A further increase in nSPS appears to be generally non-advantageous for compound potency and is analogous to the findings of Clemons et al. for highly complex molecules characterized by high FCstereo. A similar analysis was conducted for trends in target selectivity using compounds in the ChEMBL database. In order to render the analysis more reliable, the target selectivity analysis was performed only for compounds with the average pChEMBL > 5.3, thus, excluding all weakly active compounds. By analogy to the classification used by Clemons et al. and Kombo et al., the compounds were binned as highly selective (binding to only 1 protein), partially selective (binding 2-5 proteins) or as promiscuous (binding 6 or more proteins). Compounds with higher values of Fsp3 (>0.3) as well as FCstereo (>0.0) show a notable increase in the proportion of highly selective binders and a significant decrease in the proportion of the promiscuous molecules (Figure ). As in the case of the compound activity, the compounds with moderate FCstereo range have higher proportion of selective and lower proportion of promiscuous structures than compounds assigned a high FCstereo value. The obtained results for Fsp3 and FCstereo are in agreement with previous reports. Structures with low nSPS have relatively high proportion of promiscuity (12%), and low proportion of highly selective compounds (47%). Molecules with medium nSPS have a decreased proportion of promiscuous compounds (6%) and increased proportion of compounds with only 1 binder (58%). Although the bin with the high nSPS values does not have a higher proportion of highly selective compounds, its fraction of promiscuous structures decreases to below 4% (Figure ). A closer investigation of the relationship between selectivity and nSPS indicated that there is a decreasing trend in the average number of binding proteins with the increase in the nSPS values up to 20. It thus seems that the most optimal nSPS values for target selectivity are 20 and above (Figure ). The predictive powers of Fsp3, FCstereo and nSPS were assessed with respect to compound potency and promiscuity using receiver operating characteristic curves (ROC) and calculated area under the curve (AUC). We tested how well these indicators perform in terms of binary classification into compounds with high and medium-to-low potency (Figure ), as well as into promiscuous and selective molecules (Figure ) in comparison to random choice (AUC of 0.5). nSPS gave the best AUC of 0.61 in respect to potency, whereas Fsp3 and FCstereo achieved the AUC of 0.58 each. Similar performance was achieved for the classification with respect to promiscuity, where nSPS, Fsp3 and FCstereo gave the AUC of 0.60, 0.62 and 0.59, respectively. Although these results do not express high diagnostic ability, the positive performance of the assessed indicators is considerable and proves that nSPS has at least the same or better relation to potency and selectivity than the highly popular Fsp3 and FCstereo metrics.