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.
Highlights
OO H NWe report a new unified search strategy that has made it possible to identify these activity cliffs (AC) in bioactive compounds in concert applying consistent criteria, determine the overlap between different AC categories and study ACs belonging to these categories
An extended data structure based upon dual-site activity cliffs (AC) is introduced
Author contributions J Bajorath and H Hu conceived the study; H Hu carried out the analysis; H Hu and J Bajorath analyzed the results, J Bajorath and H Hu prepared the manuscript
Summary
We report a new unified search strategy that has made it possible to identify these ACs in bioactive compounds in concert applying consistent criteria, determine the overlap between different AC categories and study ACs belonging to these categories. This strategy is related to, yet distinct from the one applied in the original assessment of PS-ACs, which were most recently introduced [22], and has yielded the first public collection of PS-ACs. All new ACs identified in our systematic analysis are made freely available as a part of this study, providing a wealth of examples for follow-up investigations. Compound fragmentation To ensure consistent generation of ACs belonging to different categories, a recently introduced compound fragfuture science group www.future-science.com ds-AC iso-AC
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