Many drugs contain unique scaffolds with varying structural relationships to scaffolds of currently available bioactive compounds

• Scaffolds were systematically extracted from drugs.
• Drug scaffolds were compared to scaffolds from bioactive compounds.
• A set of 221 drug-unique scaffolds was identified.
• Structural relationships between drug-unique and bioactive scaffolds were explored.
• Many drug-unique scaffolds also displayed only limited relationships to bioactive scaffolds.

Molecular scaffolds were systematically extracted from approved drugs and analyzed. The majority of drug scaffolds, 552 of 700, were found to represent only a single drug. Moreover, 221 drug scaffolds were not detected in currently available bioactive compounds, i.e., the pool from which drug candidates usually originate. These “drug-unique” scaffolds displayed a variety of structural relationships to currently known bioactive scaffolds, reflecting rather different degrees of relatedness. Many drug-unique scaffolds formed only very limited structural relationships to bioactive scaffolds. These drug scaffolds should represent promising candidates for further chemical exploration and drug repositioning efforts and are made freely available.

Shown is a representative drug-unique scaffold (left) that is involved in three different types of structural relationships with scaffolds derived from bioactive compounds (right). Structural differences are highlighted.Figure optionsDownload as PowerPoint slide