{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T03:29:10Z","timestamp":1787887750409,"version":"build-2784847793"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"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":[[2023,10]]},"DOI":"10.1016\/j.ejmech.2023.115601","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T01:50:18Z","timestamp":1687744218000},"page":"115601","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"special_numbering":"C","title":["Disulfide-incorporated lipid prodrugs of cidofovir: Synthesis, antiviral activity, and release mechanism"],"prefix":"10.1016","volume":"258","author":[{"given":"Baogang","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binwang","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu-Chun","family":"Bei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Likun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongna","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangliang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yabin","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongquan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2023.115601_bib1","article-title":"Second meeting of the international health regulations (2005) (IHR) emergency committee regarding the multi-country outbreak of monkeypox","year":"2022","journal-title":"World Health Organization"},{"key":"10.1016\/j.ejmech.2023.115601_bib2","article-title":"2022 mpox (monkeypox) outbreak: global trends","year":"2023","journal-title":"World Health Organization"},{"key":"10.1016\/j.ejmech.2023.115601_bib3","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/s41577-022-00775-4","article-title":"Monkeypox: disease epidemiology, host immunity and clinical interventions","volume":"22","author":"Lum","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ejmech.2023.115601_bib4","doi-asserted-by":"crossref","DOI":"10.1126\/science.aaw8977","article-title":"Diverse variola virus (smallpox) strains were widespread in northern Europe in the Viking Age","volume":"369","author":"Muhlemann","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2023.115601_bib5","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.01683-19","article-title":"Drug development against smallpox: present and future","volume":"64","author":"Delaune","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2023.115601_bib6","unstructured":"Bioterrorism Agents\/Diseases, Centers for Disease Control and Prevention, https:\/\/emergency.cdc.gov\/agent\/agentlist-category.asp. 2018.."},{"key":"10.1016\/j.ejmech.2023.115601_bib7","doi-asserted-by":"crossref","first-page":"2726","DOI":"10.1128\/AAC.05983-11","article-title":"First pharmacokinetic and safety study in humans of the novel lipid antiviral conjugate CMX001, a broad-spectrum oral drug active against double-stranded DNA viruses","volume":"56","author":"Painter","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2023.115601_bib8","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1182\/blood-2016-10-748426","article-title":"The cumulative burden of double-stranded DNA virus detection after allogeneic HCT is associated with increased mortality","volume":"129","author":"Hill","year":"2017","journal-title":"Blood"},{"key":"10.1016\/j.ejmech.2023.115601_bib9","doi-asserted-by":"crossref","first-page":"7293","DOI":"10.1073\/pnas.0800200105","article-title":"Hexadecyloxypropyl-cidofovir, CMX001, prevents adenovirus-induced mortality in a permissive, immunosuppressed animal model","volume":"105","author":"Toth","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ejmech.2023.115601_bib10","first-page":"261","volume":"8","author":"Clercq","year":"1987","journal-title":"Antiviral activity of phosphotiylmethoxyalkyl derivatives of purine and pyrimidines"},{"key":"10.1016\/j.ejmech.2023.115601_bib11","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/nrd1877","article-title":"Acyclic nucleoside phosphonates: a key class of antiviral drugs","volume":"4","author":"Clercq","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2023.115601_bib12","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1128\/CMR.16.4.569-596.2003","article-title":"Clinical potential of the acyclic nucleoside phosphonates cidofovir, adefovir, and tenofovir in treatment of DNA virus and retrovirus infections","volume":"16","author":"Clercq","year":"2003","journal-title":"Clin. Microbiol. Rev."},{"key":"10.1016\/j.ejmech.2023.115601_bib13","doi-asserted-by":"crossref","first-page":"10400","DOI":"10.1021\/acs.jmedchem.6b00523","article-title":"Nucleoside phosphate and phosphonate prodrug clinical candidates","volume":"59","author":"Thornton","year":"2016","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115601_bib14","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1053\/j.ajkd.2005.02.010","article-title":"Antiviral drug-induced nephrotoxicity","volume":"45","author":"Izzedine","year":"2005","journal-title":"Am. J. Kidney Dis."},{"key":"10.1016\/j.ejmech.2023.115601_bib15","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1128\/AAC.46.4.991-995.2002","article-title":"Enhanced inhibition of orthopoxvirus replication in vitro by alkoxyalkyl esters of cidofovir and cyclic cidofovir","volume":"46","author":"Kern","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2023.115601_bib16","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1128\/AAC.46.8.2381-2386.2002","article-title":"Alkoxyalkyl esters of cidofovir and cyclic cidofovir exhibit multiple-log enhancement of antiviral activity against cytomegalovirus and herpesvirus replication in vitro","volume":"46","author":"Beadle","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2023.115601_bib17","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.tibtech.2004.06.008","article-title":"Design and development of oral drugs for the prophylaxis and treatment of smallpox infection","volume":"22","author":"Painter","year":"2004","journal-title":"Trends Biotechnol."},{"key":"10.1016\/j.ejmech.2023.115601_bib18","doi-asserted-by":"crossref","first-page":"A84","DOI":"10.1016\/j.antiviral.2009.01.005","article-title":"Alkoxyalkyl prodrugs of acyclic nucleoside phosphonates enhance oral antiviral activity and reduce toxicity: current state of the art","volume":"82","author":"Hostetler","year":"2009","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2023.115601_bib19","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0166-3542(03)00110-4","article-title":"Esterification of cidofovir with alkoxyalkanols increases oral bioavailability and diminishes drug accumulation in kidney","volume":"59","author":"Ciesla","year":"2003","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2023.115601_bib20","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1586\/14787210.2014.948847","article-title":"Development of CMX001 (Brincidofovir) for the treatment of serious diseases or conditions caused by dsDNA viruses","volume":"12","author":"Florescu","year":"2014","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"10.1016\/j.ejmech.2023.115601_bib21","doi-asserted-by":"crossref","first-page":"2726","DOI":"10.1128\/AAC.05983-11","article-title":"First pharmacokinetic and safety study in humans of the novel lipid antiviral conjugate CMX001, a broad-spectrum oral drug active against double-stranded DNA viruses","volume":"56","author":"Painter","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2023.115601_bib22","article-title":"A phase 2a study of IV BCV in subjects with adenovirus infection","year":"2022","journal-title":"ClinicalTrials.gov"},{"key":"10.1016\/j.ejmech.2023.115601_bib23","article-title":"Study to confirm of the safety and tolerability of brincidofovir in subjects with BK virus infection (Viremia) after kidney transplantation","year":"2022","journal-title":"ClinicalTrials.gov"},{"key":"10.1016\/j.ejmech.2023.115601_bib25","doi-asserted-by":"crossref","first-page":"5071","DOI":"10.1021\/cr300358b","article-title":"Disulfide-cleavage-triggered chemosensors and their biological applications","volume":"113","author":"Lee","year":"2013","journal-title":"Chem. Rev."},{"key":"10.1016\/j.ejmech.2023.115601_bib26","doi-asserted-by":"crossref","DOI":"10.1002\/marc.201900531","article-title":"Disulfide-based self-immolative linkers and functional bioconjugates for biological applications","volume":"41","author":"Deng","year":"2020","journal-title":"Macromol. Rapid Commun."},{"key":"10.1016\/j.ejmech.2023.115601_bib27","doi-asserted-by":"crossref","first-page":"7097","DOI":"10.1021\/acs.jmedchem.6b00428","article-title":"Reduction sensitive lipid conjugates of tenofovir: synthesis, stability, and antiviral activity","volume":"59","author":"Giesler","year":"2016","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115601_bib28","doi-asserted-by":"crossref","first-page":"10244","DOI":"10.1021\/acs.jmedchem.6b01292","article-title":"Next-generation reduction sensitive lipid conjugates of tenofovir: antiviral activity and mechanism of release","volume":"59","author":"Giesler","year":"2016","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115601_bib29","series-title":"Lipid Disulfide Prodrugs and Uses Related Thereto","author":"Liotta","year":"2020"},{"key":"10.1016\/j.ejmech.2023.115601_bib30","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.1016\/S0040-4039(00)76875-4","article-title":"A practical synthesis of (S)-HPMPC","volume":"35","author":"Brodfuehrer","year":"1994","journal-title":"Tetrahedron Lett."},{"key":"10.1016\/j.ejmech.2023.115601_bib31","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.antiviral.2011.04.014","article-title":"Development of Vaccinia reporter viruses for rapid, high content analysis of viral function at all stages of gene expression","volume":"91","author":"Dower","year":"2011","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2023.115601_bib32","doi-asserted-by":"crossref","first-page":"2632","DOI":"10.1128\/JVI.05416-11","article-title":"Identification of a pyridopyrimidinone inhibitor of orthopoxviruses from a diversity-oriented synthesis library","volume":"86","author":"Dower","year":"2012","journal-title":"J. Virol."},{"key":"10.1016\/j.ejmech.2023.115601_bib33","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1002\/jmv.25544","article-title":"Screening and evaluation of potential inhibitors against vaccinia virus from 767 approved drugs","volume":"91","author":"Wu","year":"2019","journal-title":"J. Med. Virol."},{"key":"10.1016\/j.ejmech.2023.115601_bib34","article-title":"Identification of small molecules with improved potency against orthopoxviruses from vaccinia to smallpox","volume":"66","author":"Brown Lauren","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2023.115601_bib35","series-title":"Handbook of Detergents: Formulation","author":"Showell","year":"2005"},{"key":"10.1016\/j.ejmech.2023.115601_bib36","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1128\/AAC.48.5.1869-1871.2004","article-title":"Inhibitory activity of alkoxyalkyl and alkyl esters of cidofovir and cyclic cidofovir against orthopoxvirus replication in vitro","volume":"48","author":"Keith","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2023.115601_bib37","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1128\/AAC.49.2.656-662.2005","article-title":"Comparison of the antiviral activities of alkoxyalkyl and alkyl esters of cidofovir against human and murine cytomegalovirus replication in vitro","volume":"49","author":"Wan","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2023.115601_bib38","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.ejpb.2014.12.010","article-title":"Micelle formulation of hexadecyloxypropyl-cidofovir (HDP-CDV) as an intravitreal long-lasting delivery system","volume":"89","author":"Ma","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.ejmech.2023.115601_bib39","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jconrel.2011.02.008","article-title":"Reduction-triggered delivery using nucleoside-lipid based carriers possessing a cleavable PEG coating","volume":"151","author":"Oumzil","year":"2011","journal-title":"J. Contr. Release"},{"key":"10.1016\/j.ejmech.2023.115601_bib40","series-title":"Formulations of Brincidofovir","author":"Ware","year":"2018"},{"key":"10.1016\/j.ejmech.2023.115601_bib41","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1021\/jm00228a025","article-title":"Effect of chain length on critical micelle formation and protein binding of quaternary ammonium compounds","volume":"19","author":"Lien","year":"1976","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115601_bib42","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0378-5173(99)00078-2","article-title":"Effects of tail alkyl chain length (n), head group structure and junction (Z) on amphiphilic properties of 1-Z-R-d,l-xylitol compounds (R=CnH2n+1)","volume":"182","author":"Savelli","year":"1999","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejmech.2023.115601_bib43","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jcis.2012.12.056","article-title":"Colloidal properties of single component naphthenic acids and complex naphthenic acid mixtures","volume":"395","author":"Mohamed","year":"2013","journal-title":"J. Colloid Interface Sci."},{"key":"10.1016\/j.ejmech.2023.115601_bib44","doi-asserted-by":"crossref","first-page":"6778","DOI":"10.1021\/jp037487t","article-title":"Micelle Formation and the hydrophobic effect","volume":"108","author":"Maibaum","year":"2004","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.ejmech.2023.115601_bib45","first-page":"416","article-title":"Tumor microenvironment responsive drug delivery systems","volume":"15","author":"He","year":"2020","journal-title":"Asian J. Pharm. Sci."},{"key":"10.1016\/j.ejmech.2023.115601_bib46","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1038\/nprot.2008.75","article-title":"Neutral red uptake assay for the estimation of cell viability\/cytotoxicity","volume":"3","author":"Repetto","year":"2008","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.ejmech.2023.115601_bib47","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0166-3542(02)00196-1","article-title":"Potential antiviral therapeutics for smallpox, monkeypox and other orthopoxvirus infections","volume":"57","author":"Baker","year":"2003","journal-title":"Antivir. Res."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523423005676?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523423005676?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T14:57:30Z","timestamp":1759330650000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523423005676"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10]]},"references-count":46,"alternative-id":["S0223523423005676"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2023.115601","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2023,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Disulfide-incorporated lipid prodrugs of cidofovir: Synthesis, antiviral activity, and release mechanism","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2023.115601","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":"115601"}}