{"entity": "publication", "iuid": "e69f1d23de31471aa11ad3d6ce0983e6", "timestamp": "2026-08-29T04:16:51.288Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e69f1d23de31471aa11ad3d6ce0983e6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e69f1d23de31471aa11ad3d6ce0983e6"}}, "title": "Identification of bioactive compounds with popular single-atom modifications: Comprehensive analysis and implications for compound design.", "authors": [{"family": "Feng", "given": "Bo", "initials": "B"}, {"family": "Yu", "given": "Hui", "initials": "H"}, {"family": "Dong", "given": "Xu", "initials": "X"}, {"family": "D\u00edaz-Holgu\u00edn", "given": "Alejandro", "initials": "A"}, {"family": "Hu", "given": "Huabin", "initials": "H"}], "type": "journal article", "published": "2025-02-05", "journal": {"title": "Eur J Med Chem", "issn": "1768-3254", "volume": "283", "pages": "117051", "issn-l": "0223-5234"}, "abstract": "The extensive bioactivity data available in public databases, such as ChEMBL, has facilitated in-depth structure-activity relationship (SAR) analysis, which are essential for understanding the impact of molecular modifications on biological activity in a comprehensive manner. A central strategy in SAR analysis is the assessment of molecular similarity. Several approaches preferred by medicinal chemists have been developed to efficiently capture structurally related compounds on a large scale. Represented as a popular molecular editing strategy in hit-to-lead and lead optimization processes, we previously introduced four types of single-atom modifications (SAMs) as chemical similarity criterion and conducted a systematic analysis of their application in compound design. In this study, we expanded the analysis to cover 10 common SAMs, including carbon-nitrogen (N\u2194C), O\u2194C, N\u2194O, S\u2194O, as well as simpler modifications such as OH\u2194H, CH3\u2194H, and halogen-hydrogen (F, Cl, Br, I\u2194H) exchanges. Leveraging high-confidence bioactivity data from ChEMBL (version 34), we assembled a comprehensive dataset comprising 374,979 SAM pairs. Following an evaluation of the frequency of these SAM types in medicinal chemistry efforts, we focused on SAM-induced activity cliffs (ACs), yielding over 7400 ACs, substantially expanding the current knowledgebase of ACs associated with single-atom changes. Furthermore, structural analysis of these ACs, supported by experimental data, provides critical insights into the role of single-atom modifications in modulating compound activity, offering practical guidance for the structure-based optimization of molecular properties in drug development. As a result, we are providing open access to all identified ACs along with their associated structural information.", "doi": "10.1016/j.ejmech.2024.117051", "pmid": "39631098", "labels": [], "xrefs": [{"db": "pii", "key": "S0223-5234(24)00933-4"}], "notes": [], "created": "2026-08-21T11:18:38.238Z", "modified": "2026-08-21T11:18:38.264Z"}