{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:31:01Z","timestamp":1787495461370,"version":"build-2736575974"},"reference-count":32,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T00:00:00Z","timestamp":1597190400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T00:00:00Z","timestamp":1597190400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T00:00:00Z","timestamp":1597190400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["P30 DA035778A1"],"award-info":[{"award-number":["P30 DA035778A1"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A traditional single-target analgesic, though it may be highly selective and potent, may not be sufficient to mitigate pain. An alternative strategy for alleviation of pain is to seek simultaneous modulation at multiple nodes in the network of pain-signaling pathways through a multitarget analgesic or drug combinations. Here we present a comprehensive pain-domain-specific chemogenomics knowledgebase (Pain-CKB) with integrated computing tools for target identification and systems pharmacology research. Pain-CKB is constructed on the basis of our established chemogenomics technology with new features, including multiple compound support, multicavity protein support, and customizable symbol display. The determination of bioactivity is also revised to avoid the use of complex machine learning models. Our one-stop computing platform describes the chemical molecules, genes, and proteins involved in pain regulation. To date, Pain-CKB has archived 272 analgesics in the market, 84 pain-related targets with 207 available 3D crystal or cryo-EM structures, and 234\u202f662 chemical agents reported for these target proteins. Moreover, Pain-CKB implements user-friendly web-interfaced computing tools and applications for the prediction and analysis of the relevant protein targets and visualization of the outputs, including HTDocking, TargetHunter, BBB permeation predictor, NGL viewer, Spider Plot, etc. The Pain-CKB server is accessible at https:\/\/www.cbligand.org\/g\/pain-ckb.<\/jats:p>","DOI":"10.1021\/acs.jcim.0c00633","type":"journal-article","created":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T12:50:30Z","timestamp":1597236630000},"page":"4429-4435","source":"Crossref","is-referenced-by-count":5,"title":["Pain-CKB, A Pain-Domain-Specific Chemogenomics Knowledgebase\nfor Target Identification and Systems Pharmacology Research"],"prefix":"10.1021","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6533-8932","authenticated-orcid":true,"given":"Zhiwei","family":"Feng","sequence":"first","affiliation":[{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maozi","family":"Chen","sequence":"additional","affiliation":[{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhe","family":"Shen","sequence":"additional","affiliation":[{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianjian","family":"Liang","sequence":"additional","affiliation":[{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6881-6175","authenticated-orcid":true,"given":"Xiang-Qun","family":"Xie","sequence":"additional","affiliation":[{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,8,12]]},"reference":[{"key":"2026081804390870900_cit1","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s13142-012-0110-2","article-title":"The future of pain research, education,\nand treatment: a summary of the IOM report \u201cRelieving pain\nin America: a blueprint for transforming prevention, care, education,\nand research\u201d","volume":"2","author":"Steglitz","year":"2012","journal-title":"Transl. Behav. Med."},{"key":"2026081804390870900_cit2","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.chiabu.2006.12.007","article-title":"Childhood abuse, chronic pain, and\ndepression in the National Comorbidity Survey","volume":"31","author":"Sachs-Ericsson","year":"2007","journal-title":"Child Abuse Neglect"},{"key":"2026081804390870900_cit3","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1146\/annurev-publhealth-031914-122957","article-title":"The prescription\nopioid and heroin\ncrisis: a public health approach to an epidemic of addiction","volume":"36","author":"Kolodny","year":"2015","journal-title":"Annu. Rev. 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Chem."},{"key":"2026081804390870900_cit7","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.drudis.2012.01.003","article-title":"A series of case\nstudies: practical methodology for identifying antinociceptive multi-target\ndrugs","volume":"17","author":"Pang","year":"2012","journal-title":"Drug Discovery Today"},{"key":"2026081804390870900_cit8","doi-asserted-by":"publisher","first-page":"D158","DOI":"10.1093\/nar\/gkw1099","article-title":"UniProt:\nthe universal\nprotein knowledgebase","volume":"45","author":"UniProt Consortium","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"2026081804390870900_cit9","doi-asserted-by":"publisher","first-page":"D464","DOI":"10.1093\/nar\/gky1004","article-title":"RCSB Protein Data Bank: biological macromolecular structures\nenabling research and education in fundamental biology, biomedicine,\nbiotechnology and energy","volume":"47","author":"Burley","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2026081804390870900_cit10","doi-asserted-by":"publisher","first-page":"D1121","DOI":"10.1093\/nar\/gkx1076","article-title":"Therapeutic\ntarget database update 2018: enriched resource for facilitating bench-to-clinic\nresearch of targeted therapeutics","volume":"46","author":"Li","year":"2018","journal-title":"Nucleic Acids\nRes."},{"key":"2026081804390870900_cit11","doi-asserted-by":"publisher","first-page":"D1118","DOI":"10.1093\/nar\/gkt1129","article-title":"Therapeutic\ntarget database update 2014: a resource\nfor targeted therapeutics","volume":"42","author":"Qin","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2026081804390870900_cit12","doi-asserted-by":"publisher","first-page":"D1031","DOI":"10.1093\/nar\/gkz981","article-title":"Therapeutic target database 2020:\nenriched resource for facilitating\nresearch and early development of targeted therapeutics","volume":"48","author":"Wang","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2026081804390870900_cit13","doi-asserted-by":"publisher","first-page":"D1069","DOI":"10.1093\/nar\/gkv1230","article-title":"Therapeutic target\ndatabase update 2016: enriched resource for bench to clinical drug\ntarget and targeted pathway information","volume":"44","author":"Yang","year":"2016","journal-title":"Nucleic\nAcids Res."},{"key":"2026081804390870900_cit14","doi-asserted-by":"publisher","first-page":"D787","DOI":"10.1093\/nar\/gkp1014","article-title":"Update of TTD: Therapeutic Target Database","volume":"38","author":"Zhu","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2026081804390870900_cit15","doi-asserted-by":"publisher","first-page":"D1128","DOI":"10.1093\/nar\/gkr797","article-title":"Therapeutic target database update\n2012: a resource for facilitating target-oriented drug discovery","volume":"40","author":"Zhu","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2026081804390870900_cit16","doi-asserted-by":"publisher","first-page":"D1100","DOI":"10.1093\/nar\/gkr777","article-title":"ChEMBL:\na large-scale bioactivity database for drug discovery","volume":"40","author":"Gaulton","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2026081804390870900_cit17","doi-asserted-by":"publisher","first-page":"D1074","DOI":"10.1093\/nar\/gkx1037","article-title":"DrugBank 5.0: a major update to the DrugBank database\nfor 2018","volume":"46","author":"Wishart","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2026081804390870900_cit18","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1021\/acs.jcim.8b00623","article-title":"DAKB-GPCRs:\nAn Integrated Computational Platform for Drug Abuse Related GPCRs","volume":"59","author":"Chen","year":"2019","journal-title":"J. Chem. Inf. Model."},{"key":"2026081804390870900_cit19","doi-asserted-by":"publisher","first-page":"3486","DOI":"10.1021\/acschemneuro.9b00109","article-title":"Computational\nSystems\nPharmacology-Target Mapping for Fentanyl-Laced Cocaine Overdose","volume":"10","author":"Cheng","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"2026081804390870900_cit20","doi-asserted-by":"publisher","first-page":"2428","DOI":"10.1021\/acsomega.9b03960","article-title":"Insight into Ginkgo\nbiloba L. 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