{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T08:54:16Z","timestamp":1785228856649,"version":"3.55.0"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2023,9]]},"DOI":"10.1016\/j.ejmech.2023.115532","type":"journal-article","created":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T21:32:04Z","timestamp":1685914324000},"page":"115532","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"special_numbering":"C","title":["Identification of 5-[5-cyano-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxamido] thiazole-4-carboxylic acid as a promising dual inhibitor of urate transporter 1 and xanthine oxidase"],"prefix":"10.1016","volume":"257","author":[{"given":"Fengwei","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyang","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuhua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaojie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2023.115532_bib1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.addr.2007.06.011","article-title":"PEG-uricase in the management of treatment-resistant gout and hyperuricemia","volume":"60","author":"Sherman","year":"2008","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.ejmech.2023.115532_bib2","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.jare.2017.03.003","article-title":"Physiological functions and pathogenic potential of uric acid: a review","volume":"8","author":"El Ridi","year":"2017","journal-title":"J. Adv. Res."},{"key":"10.1016\/j.ejmech.2023.115532_bib3","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.autrev.2012.07.024","article-title":"Gout as autoinflammatory disease: new mechanisms for more appropriated treatment targets","volume":"12","author":"Punzi","year":"2012","journal-title":"Autoimmun. Rev."},{"key":"10.1016\/j.ejmech.2023.115532_bib4","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/s41598-017-00706-7","article-title":"Discovery and characterization of verinurad, a potent and specific inhibitor of URAT1 for the treatment of hyperuricemia and gout","volume":"7","author":"Tan","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejmech.2023.115532_bib5","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s11926-016-0587-7","article-title":"Urate handling in the human body","volume":"18","author":"Hyndman","year":"2016","journal-title":"Curr. Rheumatol. Rep."},{"key":"10.1016\/j.ejmech.2023.115532_bib6","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s42358-019-0080-x","article-title":"Benzbromarone in the treatment of gout","volume":"59","author":"Azevedo","year":"2019","journal-title":"Adv. Rheumatol."},{"key":"10.1016\/j.ejmech.2023.115532_bib7","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1097\/BOR.0000000000000146","article-title":"New medications in development for the treatment of hyperuricemia of gout","volume":"27","author":"Diaz-Torne","year":"2015","journal-title":"Curr. Opin. Rheumatol."},{"key":"10.1016\/j.ejmech.2023.115532_bib8","doi-asserted-by":"crossref","first-page":"F361","DOI":"10.1152\/ajprenal.00207.2006","article-title":"Renal expression of organic anion transporter OAT2 in rats and mice is regulated by sex hormones","volume":"292","author":"Ljubojevic","year":"2007","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"10.1016\/j.ejmech.2023.115532_bib9","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1002\/art.27327","article-title":"High versus low dosing of oral colchicine for early acute gout flare: twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study","volume":"62","author":"Terkeltaub","year":"2010","journal-title":"Arthritis Rheum."},{"key":"10.1016\/j.ejmech.2023.115532_bib10","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1021\/acs.jmedchem.1c02057","article-title":"Discovery of novel bicyclic imidazolopyridine-containing human urate transporter 1 inhibitors as hypouricemic drug candidates with improved efficacy and favorable druggability","volume":"65","author":"Zhao","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115532_bib11","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s40265-016-0550-y","article-title":"Lesinurad: first global approval","volume":"76","author":"Hoy","year":"2016","journal-title":"Drugs"},{"key":"10.1016\/j.ejmech.2023.115532_bib12","doi-asserted-by":"crossref","first-page":"179","DOI":"10.2165\/00003495-198020030-00002","article-title":"Sulfinpyrazone: a review of its pharmacological properties and therapeutic use","volume":"20","author":"Margulies","year":"1980","journal-title":"Drugs"},{"key":"10.1016\/j.ejmech.2023.115532_bib13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12012-011-9145-8","article-title":"The history and future of probenecid","volume":"12","author":"Robbins","year":"2012","journal-title":"Cardiovasc. Toxicol."},{"key":"10.1016\/j.ejmech.2023.115532_bib14","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1021\/acsmedchemlett.0c00176","article-title":"Discovery of dotinurad (FYU-981), a new phenol derivative with highly potent uric acid lowering activity","volume":"11","author":"Uda","year":"2020","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2023.115532_bib15","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1080\/14740338.2019.1594771","article-title":"Safety and tolerability of available urate-lowering drugs: a critical review","volume":"18","author":"Strilchuk","year":"2019","journal-title":"Expet Opin. Drug Saf."},{"key":"10.1016\/j.ejmech.2023.115532_bib16","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1124\/dmd.117.077818","article-title":"Metabolic epoxidation is a critical step for the development of benzbromarone-induced hepatotoxicity","volume":"45","author":"Wang","year":"2017","journal-title":"Drug Metabol. Dispos.: Biol. Fate. Chem"},{"key":"10.1016\/j.ejmech.2023.115532_bib17","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1002\/phar.2609","article-title":"The association between urate-lowering therapies and treatment-related adverse events, liver damage, and major adverse cardiovascular events (MACE): a network meta-analysis of randomized trials","volume":"41","author":"Zhang","year":"2021","journal-title":"Pharmacotherapy"},{"key":"10.1016\/j.ejmech.2023.115532_bib18","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.phrs.2014.10.009","article-title":"Tranilast: a review of its therapeutic applications","volume":"91","author":"Darakhshan","year":"2015","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.ejmech.2023.115532_bib19","doi-asserted-by":"crossref","DOI":"10.1002\/prp2.291","article-title":"Uricosuric targets of tranilast","volume":"5","author":"Mandal","year":"2017","journal-title":"Pharmacol. Res. Perspect."},{"key":"10.1016\/j.ejmech.2023.115532_bib20","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1177\/1759720X16646703","article-title":"Treatment of hyperuricemia in gout: current therapeutic options, latest developments and clinical implications","volume":"8","author":"Sattui","year":"2016","journal-title":"Ther. Adv. Muscoskel. Dis."},{"key":"10.1016\/j.ejmech.2023.115532_bib21","doi-asserted-by":"crossref","first-page":"7772","DOI":"10.53730\/ijhs.v6nS2.6926","article-title":"Pharmacological overview for therapy of gout and hyperuricemia","author":"Yadav","year":"2022","journal-title":"Int. J. Health Sci."},{"key":"10.1016\/j.ejmech.2023.115532_bib22","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.201708689","article-title":"Tranilast directly targets NLRP3 to treat inflammasome-driven diseases","volume":"10","author":"Huang","year":"2018","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.ejmech.2023.115532_bib23","doi-asserted-by":"crossref","DOI":"10.1016\/j.coph.2022.102241","article-title":"Emerging strategies for treating gout","volume":"65","author":"Huddleston","year":"2022","journal-title":"Curr. Opin. Pharmacol."},{"key":"10.1016\/j.ejmech.2023.115532_bib24","doi-asserted-by":"crossref","first-page":"885","DOI":"10.4155\/fmc.14.50","article-title":"Conformational restriction: an effective tactic in 'follow-on'-based drug discovery","volume":"6","author":"Fang","year":"2014","journal-title":"Future Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115532_bib25","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ejmech.2017.04.003","article-title":"Indoles as therapeutics of interest in medicinal chemistry: bird's eye view","volume":"134","author":"Chadha","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115532_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2019.103021","article-title":"Medicinal chemistry of indole derivatives: current to future therapeutic prospectives","volume":"89","author":"Kumari","year":"2019","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2023.115532_bib27","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.ejmech.2014.10.065","article-title":"A review on recent developments of indole-containing antiviral agents","volume":"89","author":"Zhang","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115532_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2020.112077","article-title":"Design, synthesis and biological evaluation of 1-alkyl-5\/6-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-1H-indole-3-carbonitriles as novel xanthine oxidase inhibitors","volume":"190","author":"Gao","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115532_bib29","doi-asserted-by":"crossref","DOI":"10.1155\/2016\/8952520","article-title":"Tryptophan biochemistry: structural, nutritional, metabolic, and medical aspects in humans","volume":"2016","author":"Palego","year":"2016","journal-title":"J. Amino Acids"},{"key":"10.1016\/j.ejmech.2023.115532_bib30","series-title":"Indole Derivative and its Preparation Method and Application in Preparation of Drug for Treating And\/or Preventing Hyperuricemia and Gout, Chinese Patent Application #CN105789221A","author":"Wang","year":"2021"},{"key":"10.1016\/j.ejmech.2023.115532_bib31","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/s41401-021-00640-5","article-title":"CDER167, a dual inhibitor of URAT1 and GLUT9, is a novel and potent uricosuric candidate for the treatment of hyperuricemia","volume":"43","author":"Zhao","year":"2022","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.ejmech.2023.115532_bib32","article-title":"Recent updates of natural and synthetic URAT1 inhibitors and novel screening methods","volume":"2021","author":"Chen","year":"2021","journal-title":"Evid. base Compl. Alternative Med."},{"key":"10.1016\/j.ejmech.2023.115532_bib33","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1080\/13543776.2019.1676727","article-title":"Novel urate transporter 1 (URAT1) inhibitors: a review of recent patent literature (2016-2019)","volume":"29","author":"Dong","year":"2019","journal-title":"Expert Opin. Ther. Pat."},{"key":"10.1016\/j.ejmech.2023.115532_bib34","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2023.115532_bib35","doi-asserted-by":"crossref","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","article-title":"AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models","volume":"50","author":"Varadi","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ejmech.2023.115532_bib36","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/j.bmcl.2015.01.055","article-title":"Design and synthesis of novel 2-(indol-5-yl)thiazole derivatives as xanthine oxidase inhibitors","volume":"25","author":"Song","year":"2015","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.ejmech.2023.115532_bib37","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.semarthrit.2018.06.004","article-title":"Combination urate-lowering therapy in the treatment of gout: what is the evidence?","volume":"48","author":"Perez-Ruiz","year":"2019","journal-title":"Semin. Arthritis Rheum."},{"key":"10.1016\/j.ejmech.2023.115532_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2019.103564","article-title":"Novel 3-[4-alkoxy-3-(1H-tetrazol-1-yl) phenyl]-1,2,4-oxadiazol-5(4H)-ones as promising xanthine oxidase inhibitors: design, synthesis and biological evaluation","volume":"95","author":"Gao","year":"2020","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2023.115532_bib39","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1016\/j.bmcl.2017.06.059","article-title":"Synthesis and evaluation of 1-phenyl-1H-1,2,3-triazole-4-carboxylic acid derivatives as xanthine oxidase inhibitors","volume":"27","author":"Zhang","year":"2017","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.ejmech.2023.115532_bib40","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.ejmech.2018.01.060","article-title":"Design, synthesis and biological evaluation of 1-hydroxy-2-phenyl-4-pyridyl-1H-imidazole derivatives as xanthine oxidase inhibitors","volume":"146","author":"Zhang","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115532_bib41","doi-asserted-by":"crossref","first-page":"4192","DOI":"10.1016\/j.bmcl.2014.07.041","article-title":"Synthesis and evaluation of naphthoflavones as a new class of non purine xanthine oxidase inhibitors","volume":"24","author":"Singh","year":"2014","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.ejmech.2023.115532_bib42","first-page":"1","article-title":"Design, synthesis and evaluation of 2,4-diarylpyrano[3,2-c]chromen-5(4H)-one as a new class of non-purine xanthine oxidase inhibitors","volume":"30","author":"Virdi","year":"2014","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115532_bib43","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1039\/C8MD00512E","article-title":"Benzoflavone derivatives as potent antihyperuricemic agents","volume":"10","author":"Singh","year":"2019","journal-title":"Medchemcomm"},{"key":"10.1016\/j.ejmech.2023.115532_bib44","series-title":"01; Chemical Computing Group ULC, 1010 Sherbrooke St. West, Suite #910","volume":"2R7","author":"Molecular Operating Environment (Moe)","year":"2019"},{"key":"10.1016\/j.ejmech.2023.115532_bib45","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2021.113928","article-title":"Design, synthesis, and biological evaluation of N-(3-cyano-1H-indol-5\/6-yl)-6-oxo-1,6-dihydropyrimidine-4-carboxamides and 5-(6-oxo-1,6-dihydropyrimidin-2-yl)-1H-indole-3-carbonitriles as novel xanthine oxidase inhibitors","volume":"227","author":"Zhang","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115532_bib46","unstructured":"SPSS Inc, (Chicago, IL, USA).."},{"key":"10.1016\/j.ejmech.2023.115532_bib47","unstructured":"One-way ANOVA followed by Dunnett's multiple comparisons test was performed using GraphPad Prism version 7.0.0 for Windows, GraphPad Software, San Diego, California USA, www.graphpad.com.."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523423004981?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523423004981?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T14:53:16Z","timestamp":1730991196000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523423004981"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9]]},"references-count":47,"alternative-id":["S0223523423004981"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2023.115532","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2023,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Identification of 5-[5-cyano-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxamido] thiazole-4-carboxylic acid as a promising dual inhibitor of urate transporter 1 and xanthine oxidase","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2023.115532","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"115532"}}