Increasing the public activity cliff knowledge base with new categories of activity cliffs

Abstract

Aim: Extending the public knowledge base of activity cliffs (ACs) with new categories of ACs having special structural characteristics. Methodology: Dual-site ACs, isomer ACs and ACs with privileged substructures are described and their systematic identification is detailed. Exemplary results & data: More than 7400 new ACs belonging to different categories with activity against more than 200 targets were identified and are made publicly available. Limitations & next steps: For dual-site ACs, limited numbers of isomers are available as structural analogs for rationalizing contributions to AC formation. The search for such analogs will continue. In addition, the target distribution of ACs containing privileged substructures will be further analyzed.

Keywords

• active compounds
• activity cliffs
• computational analysis
• medicinal chemistry
• open access data
• privileged substructures