We have developed a strategy that gives rapid access to a large number of structurally different PNPs from commercial sources. To this end, we developed an improved version of the natural product fragment combination (NPFC) tool which identifies and classifies PNPs by identifying NP fragments and their combination types in chemical structures. Using this tool, we analyzed the full library of 3.5M synthetic small molecules and screening libraries, which are available and widely sourced by the scientific community from Enamine for PNP content, as a proxy for potential future bioactive compounds. For possible correlation of structural complexity with degree of bioactivity, the spatial complexity of the Enamine library was assessed using the normalized Spatial Score (nSPS). Bioactivity of a selected subset of PNPs obtained from Enamine was determined in the unbiased morphological cell painting assay (CPA), and compared to the performance of a PNP collection synthesized in the course of research projects aimed at the establishment of the PNP principle. The analysis revealed that 32% of the Enamine library are PNPs with predominant fragment composition and combinations that resemble PNPs identified in the most recently released ChEMBL 32 dataset. Enamine-PNPs contain a significant number of compounds with unexpected and probably new bioactivity.