We have shown recently a correlation of target-based activity with nSPS scores between 20-40, and demonstrated for selected PNP classes enriched in bioactivity that for them the nSPS also falls into this range. However, there is no direct correlation between the nSPS and activity in the CPA employed here as one of many possible measures of bioactivity, probably because of the unbiased nature of the assay and the experience that it also detects non-target related compound activity, like e.g. lysosomotropism and cholesterol homeostasis impairment. Still, an nSPS in the range of 20-40 will probably be advantageous. In addition, based on findings with our in-house data, there is a positive correlation between molecular weight and the hit rate in CPA (fig. ; fig. S2b from ref. ). These two findings together may explain the hit rate observed for the selected Enamine-PNPs. Indeed, although molecular weight has been identified before as a limiting property in the performance of compound collections, the design of the Enamine collection does reflect the generally higher demand of the medicinal chemistry community for compounds with lower molecular weight, which is also reflected in the compounds selected here for biological analysis.