Counts of all NP fragments, fragment pair combinations, and PNP fragment pair combinations occurring in the post-2008 Clinical and Reference compounds are summarised in Table . The fragment pair combinations can have more than one of each fragment type present. Of the 1673 individual fragments in the NP library, it is notable that only 176 (10.6%) are used in Clinical compounds, and a further 296 (17.7%) are unique to Reference compounds (Table ). However, the 176 Clinical fragments comprise 97.8% of the total fragment coverage seen in Reference compounds. For the much higher numbers of fragment pair combinations, there is lower coverage by Clinical compounds (e.g. 72.8% for all fragment pairs and 63.1% for all fragment pair PNP combinations, Table ) and Reference-only fragment pairs outnumber Clinical fragment pairs by upto 10-fold across major target classes (e.g. GPCRs, Table ). Reference singleton counts are dominant in both classes of fragment pairs. The occurrence of the most common fragments and fragment combinations seen in all post-2008 Clinical compounds was compared to that seen in the Reference compounds. The 58 most common fragments, occurring ≥8 times in Clinical compounds (Figure ), account for 90.5% of the total Clinical fragment occurrence. Of the 58 fragments, 15 (26%) occur significantly more frequently in Clinical versus Reference compounds (by odds ratio, p <0.05), and 4 (7%) are significantly increased in Reference compounds (Figure ). The 30 most common Clinical fragment pair combinations (Figure ), occurring ≥14 times, account for 22% of the total Clinical fragment occurrence and 10 of these (33%) are significantly more abundant clinically. Similar Clinical preferences are seen for the 31 most common PNP combinations, occurring ≥8 times and accounting for 22% of the total Clinical occurrence (Figure ). It is apparent from Figures and that the pyrrolidine and cyclopropyl rings feature prominently, individually and in combination with other fragments, as having higher abundance in Clinical over Reference compounds.