{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T15:36:08Z","timestamp":1780414568641,"version":"3.54.1"},"reference-count":76,"publisher":"American Chemical Society (ACS)","issue":"16","license":[{"start":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T00:00:00Z","timestamp":1691539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA045473"],"award-info":[{"award-number":["DA045473"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Chem. Inf. Model."],"published-print":{"date-parts":[[2023,8,28]]},"DOI":"10.1021\/acs.jcim.3c00651","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T08:00:35Z","timestamp":1691568035000},"page":"5056-5065","source":"Crossref","is-referenced-by-count":20,"title":["De Novo Design of \u03ba-Opioid Receptor Antagonists Using a Generative Deep-Learning Framework"],"prefix":"10.1021","volume":"63","author":[{"given":"Leslie","family":"Salas-Estrada","sequence":"first","affiliation":[{"name":"Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2868-303X","authenticated-orcid":true,"given":"Davide","family":"Provasi","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5327-832X","authenticated-orcid":true,"given":"Husnu \u00dcmit","family":"Kaniskan","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi-Ping","family":"Huang","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health, Psychoactive Drug Screening Program, Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey F.","family":"DiBerto","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health, Psychoactive Drug Screening Program, Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Marcelo","family":"Lamim Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2387-3862","authenticated-orcid":true,"given":"Jian","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States"},{"name":"Mount Sinai Center for Therapeutics Discovery, Departments of Oncological Sciences and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0561-6520","authenticated-orcid":true,"given":"Bryan L.","family":"Roth","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health, Psychoactive Drug Screening Program, Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, United States"},{"name":"Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill Eshelman School of Pharmacy, Chapel Hill, North Carolina 27599, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4382-8276","authenticated-orcid":true,"given":"Marta","family":"Filizola","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2023,8,9]]},"reference":[{"key":"ref1\/cit1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-33823-9_2"},{"key":"ref2\/cit2","unstructured":"Azadfraf, M. H.; M R; Leaming, J. M. Opioid Addiction\n                      StatPearls\n                      2022."},{"key":"ref3\/cit3","unstructured":"U.S. Overdose Deaths in\n2021 Increased Half as Much as in 2020 - But Are Still Up 15%\n                      . CDC\/NCHS, Ed. 2022."},{"key":"ref4\/cit4","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7006a4"},{"key":"ref5\/cit5","unstructured":"UNODC.\n                      World Drug Report\n2021\n                      . Ed. 2021."},{"key":"ref6\/cit6","unstructured":"CDC.\n                      Emergency Preparedness\nand Response. Increase in Fatal Drug Overdoses Across the United States\nDriven by Synthetic Opioids Before and During the COVID-19 Pandemic\n                      . Ed. 2020."},{"key":"ref7\/cit7","unstructured":"FDA.\n                      FDA\u2032S 2018 Strategic\nPolicy Roadmap. Healthy Innovation, Safer Families\n                      , Ed. 2018."},{"key":"ref8\/cit8","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6626a4"},{"key":"ref9\/cit9","unstructured":"NIH.\n                      NIH HEAL Initiative\nResearch Plan\n                      . Ed. 2023."},{"key":"ref10\/cit10","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-018-0292-5"},{"key":"ref11\/cit11","doi-asserted-by":"publisher","DOI":"10.1002\/da.22500"},{"key":"ref12\/cit12","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1979-13.2013"},{"key":"ref13\/cit13","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100503"},{"key":"ref14\/cit14","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2006.10.002"},{"key":"ref15\/cit15","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200620090-00001"},{"key":"ref16\/cit16","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145701002632"},{"key":"ref17\/cit17","first-page":"151","volume":"284","author":"Xi Z. X.","year":"1998","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref18\/cit18","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.127415"},{"key":"ref19\/cit19","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-005-0167-4"},{"key":"ref20\/cit20","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90329-j"},{"key":"ref21\/cit21","doi-asserted-by":"publisher","DOI":"10.1124\/mol.111.074195"},{"key":"ref22\/cit22","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2011.05.021"},{"key":"ref23\/cit23","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2012.151"},{"key":"ref24\/cit24","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2014.03.040"},{"key":"ref25\/cit25","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.1166"},{"key":"ref26\/cit26","unstructured":"Austin, D. H. T.\n                      Research and Development in the Pharmaceutical Industry\n                      , Congressional Budget Office, 2021."},{"key":"ref27\/cit27","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat2663"},{"key":"ref28\/cit28","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14073"},{"key":"ref29\/cit29","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.7b00346"},{"key":"ref30\/cit30","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.7b01137"},{"key":"ref31\/cit31","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.8b00474"},{"key":"ref32\/cit32","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.8b00839"},{"key":"ref33\/cit33","doi-asserted-by":"publisher","DOI":"10.1038\/nature25978"},{"key":"ref34\/cit34","doi-asserted-by":"publisher","DOI":"10.1002\/minf.201700153"},{"key":"ref35\/cit35","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b00494"},{"key":"ref36\/cit36","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.7b00690"},{"key":"ref37\/cit37","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c00927"},{"key":"ref38\/cit38","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.1608"},{"key":"ref39\/cit39","doi-asserted-by":"publisher","DOI":"10.48550\/ARXIV.2212.13295"},{"key":"ref40\/cit40","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0224-x"},{"key":"ref41\/cit41","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv352"},{"key":"ref42\/cit42","doi-asserted-by":"publisher","DOI":"10.1038\/nature10939"},{"key":"ref43\/cit43","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.0c00675"},{"key":"ref44\/cit44","doi-asserted-by":"publisher","DOI":"10.1021\/jm901137j"},{"key":"ref45\/cit45","doi-asserted-by":"publisher","DOI":"10.2174\/1389200054021799"},{"key":"ref46\/cit46","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.1.1.91"},{"key":"ref47\/cit47","doi-asserted-by":"publisher","DOI":"10.1021\/jm9602928"},{"key":"ref48\/cit48","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.565644"},{"key":"ref49\/cit49","doi-asserted-by":"publisher","DOI":"10.1021\/jm000942e"},{"key":"ref50\/cit50","unstructured":"RDKit:\n                      Open-source\ncheminformatics\n                      ; 2010. https:\/\/www.rdkit.org\/."},{"key":"ref51\/cit51","doi-asserted-by":"publisher","DOI":"10.1021\/ci990307l"},{"key":"ref52\/cit52","doi-asserted-by":"publisher","DOI":"10.1021\/ci034243x"},{"key":"ref53\/cit53","unstructured":"Kingma, D. P. B.; J A In\n                      A method for stochastic optimization\n                      , 3rd International Conference for Learning Representations, San Diego, CA, US, 2015."},{"key":"ref54\/cit54","unstructured":"OpenEye Python Toolkits. OpenEye, Cadence Molecular Sciences: Santa Fe, NM 2021 http:\/\/www.eyesopen.com."},{"key":"ref55\/cit55","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.200800178"},{"key":"ref56\/cit56","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.8b00234"},{"key":"ref57\/cit57","doi-asserted-by":"publisher","DOI":"10.1007\/BF00992696"},{"key":"ref58\/cit58","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2021.116308"},{"key":"ref59\/cit59","unstructured":"Quacpac ToolkitOpen. Eye, Cadence Molecular Sciences: Santa Fe, NM, 2021, http:\/\/www.eyesopen.com."},{"key":"ref60\/cit60","unstructured":"Omega Toolkit. OpenEye,\nCadence Molecular Sciences: Santa Fe, NM, 2021, http:\/\/www.eyesopen.com."},{"key":"ref61\/cit61","doi-asserted-by":"publisher","DOI":"10.1186\/1758-2946-4-27"},{"key":"ref62\/cit62","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.8b00684"},{"key":"ref63\/cit63","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201700505"},{"key":"ref64\/cit64","unstructured":"Bannan, C. OE_toandfrom_RDK.ipynb. https:\/\/gist.github.com\/bannanc\/810ccc4636b930a4522636baab1965a6."},{"key":"ref65\/cit65","unstructured":"LigPrep,\nProtein Preparation\nWizard, QikProp, and Glide. Schr\u00f6dinger, LLCNew York, NY\n                      , 2020."},{"key":"ref66\/cit66","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.8b01026"},{"key":"ref67\/cit67","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3235"},{"key":"ref68\/cit68","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3943"},{"key":"ref69\/cit69","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201600182"},{"key":"ref70\/cit70","doi-asserted-by":"publisher","DOI":"10.1016\/s0169-409x(02)00008-x"},{"key":"ref71\/cit71","doi-asserted-by":"publisher","DOI":"10.1186\/1758-2946-1-8"},{"key":"ref72\/cit72","first-page":"6410","author":"You J.","year":"2018","journal-title":"Adv. Neurol. Inf. Process. Syst."},{"key":"ref73\/cit73","unstructured":"GraphPad\nPrism\n                      ; GraphPad Software: San Diego, California, US www.graphpad.com."},{"key":"ref74\/cit74","first-page":"366","volume-title":"Methods in Neurosciences","volume":"25","author":"Ballesteros J. A.","year":"1995"},{"key":"ref75\/cit75","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2014.11.001"},{"key":"ref76\/cit76","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1010"}],"container-title":["Journal of Chemical Information and Modeling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jcim.3c00651","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jcim.3c00651","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T04:34:38Z","timestamp":1693197278000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jcim.3c00651"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,9]]},"references-count":76,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2023,8,28]]}},"alternative-id":["10.1021\/acs.jcim.3c00651"],"URL":"https:\/\/doi.org\/10.1021\/acs.jcim.3c00651","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.04.25.537995","asserted-by":"object"}]},"ISSN":["1549-9596","1549-960X"],"issn-type":[{"value":"1549-9596","type":"print"},{"value":"1549-960X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,9]]}}}