{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T15:04:53Z","timestamp":1770563093561,"version":"3.49.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":38,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The supervision of novel psychoactive substances (NPSs) is a global problem, and the regulation of NPSs was heavily relied on identifying structural matches in established NPSs databases. However, violators could circumvent legal oversight by altering the side chain structure of recognized NPSs and the existing methods cannot overcome the inaccuracy and lag of supervision. In this study, we propose a scaffold and transformer-based NPS generation and Screening (STNGS) framework to systematically identify and evaluate potential NPSs. A scaffold-based generative model and a rank function with four parts are contained by our framework. Our generative model shows excellent performance in the design and optimization of general molecules and NPS-like molecules by chemical space analysis and property distribution analysis. The rank function includes synthetic accessibility score and frequency score, as well as confidence score and affinity score evaluated by a neural network, which enables the precise positioning of potential NPSs. Applied STNGS framework with molecular docking and a G protein-coupled receptor (GPCR) activation-based sensor (GRAB), we successfully identify three novel synthetic cannabinoids with activity. STNGS constrains the chemical space to generate NPS-like molecules database with diversity and novelty, which assists in the ex-ante regulation of NPSs.<\/jats:p>","DOI":"10.1093\/bib\/bbae690","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T01:29:41Z","timestamp":1735608581000},"source":"Crossref","is-referenced-by-count":5,"title":["STNGS: a deep scaffold learning-driven generation and screening framework for discovering potential novel psychoactive substances"],"prefix":"10.1093","volume":"26","author":[{"given":"Dongping","family":"Liu","sequence":"first","affiliation":[{"name":"School of Science, China Pharmaceutical University , Nanjing 211198 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinghao","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Science, China Pharmaceutical University , Nanjing 211198 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,","place":["China"]},{"name":"Office of China National Narcotics Control Commission, China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control , Beijing 100193 ,","place":["China"]},{"name":"School of Pharmacy, China Pharmaceutical University , Nanjing 211198 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shangxuan","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Peking University School of Life Sciences , Beijing 100871 ,","place":["China"]},{"name":"PKU-IDG\/McGovern Institute for Brain Research , Beijing 100871 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulong","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Peking University School of Life Sciences , Beijing 100871 ,","place":["China"]},{"name":"PKU-IDG\/McGovern Institute for Brain Research , Beijing 100871 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jubo","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, China Pharmaceutical University , Nanjing 211198 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyang","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhejiang Lab , Hangzhou 311500 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Engineering, China Pharmaceutical University , Nanjing 211198 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Drug Monitoring and Control, Drug Intelligence and Forensic Center, Ministry of Public Security , Beijing 100193 ,","place":["China"]},{"name":"Office of China National Narcotics Control Commission, China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control , Beijing 100193 ,","place":["China"]},{"name":"School of Pharmacy, China Pharmaceutical University , Nanjing 211198 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Di","sequence":"additional","affiliation":[{"name":"Office of China National Narcotics Control Commission, China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control , Beijing 100193 ,","place":["China"]},{"name":"School of Pharmacy, China Pharmaceutical University , Nanjing 211198 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0617-5840","authenticated-orcid":false,"given":"Jun","family":"Liao","sequence":"additional","affiliation":[{"name":"School of Science, China Pharmaceutical University , Nanjing 211198 ,","place":["China"]},{"name":"Office of China National Narcotics 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