Though we focused our analysis on the Enamine 350/3 database (vide supra), we sought to ascertain whether the trends that emerged are consistent with those from the smaller Mcule database presented in Figure . Despite the difference in size (by orders of magnitude) between the Enamine and Mcule databases, the same trends emerged in our analysis. The Mcule (Figure ) database also indicates that the same transformations identified in our analysis of the Enamine database give the lowest percentages of commercial products. For example, the pyrazole-to-furan conversion gives products with the lowest percentages of commercial compounds in both databases (0.20%). Similarly, other multiple-atom transformations, such as the isoxazole-toimidazole, oxazole-to-pyrazole, and furan-to-imidazole virtual skeletal edits, give lower percentages (0.36%-1.02%) of commercial products. However, the bias toward these multipleatom transformations over single-atom skeletal edits is not as pronounced as in the Enamine database.