{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:14:17Z","timestamp":1791976457916,"version":"4.4.0"},"reference-count":62,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100010035","name":"Outstanding Youth Foundation of Jiangsu Province of China","doi-asserted-by":"publisher","award":["BK20200081"],"award-info":[{"award-number":["BK20200081"]}],"id":[{"id":"10.13039\/501100010035","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173686"],"award-info":[{"award-number":["82173686"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973186"],"award-info":[{"award-number":["81973186"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.ejmech.2025.118146","type":"journal-article","created":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T22:28:39Z","timestamp":1757284119000},"page":"118146","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"special_numbering":"C","title":["Design, synthesis, and anti-cancer evaluation of NQO1-responsive prodrug of gemcitabine"],"prefix":"10.1016","volume":"300","author":[{"given":"Tian-Yu","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze-Tao","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangji","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Zhen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"4","key":"10.1016\/j.ejmech.2025.118146_bib1","first-page":"394","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"70","author":"Bray","year":"2020","journal-title":"CA Cancer J. Clin."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118146_bib2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/nrc1529","article-title":"Chemotherapy and the war on cancer","volume":"5","author":"Chabner","year":"2005","journal-title":"Nat. Rev. Cancer"},{"issue":"8","key":"10.1016\/j.ejmech.2025.118146_bib3","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.addr.2011.02.002","article-title":"Prodrugs for improving tumor targetability and efficiency","volume":"63","author":"Mahato","year":"2011","journal-title":"Adv. Drug Deliv. Rev."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118146_bib4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1023\/A:1016370407633","article-title":"The potential of nucleotide analogs as inhibitors of retroviruses and tumors","volume":"1","author":"Robins","year":"1984","journal-title":"Pharm. Res."},{"issue":"4","key":"10.1016\/j.ejmech.2025.118146_bib5","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S0006-2952(99)00035-0","article-title":"Role of antimetabolites of purine and pyrimidine nucleotide metabolism in tumor cell differentiation","volume":"58","author":"Hatse","year":"1999","journal-title":"Biochem. Pharmacol."},{"issue":"11","key":"10.1016\/j.ejmech.2025.118146_bib6","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1021\/jo00246a002","article-title":"Synthesis of 2-deoxy-2,2-difluoro-D-ribose and 2\u2032-deoxy-2\u2032,2\u2032-difluoro-D-ribo-furanosyl nucleosides","volume":"53","author":"Hertel","year":"1988","journal-title":"J. Org. Chem."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118146_bib7","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/bjc.1996.18","article-title":"Phase II study of gemcitabine in patients with advanced pancreatic cancer","volume":"73","author":"Carmichael","year":"1996","journal-title":"Br. J. Cancer"},{"issue":"14","key":"10.1016\/j.ejmech.2025.118146_bib8","first-page":"4417","article-title":"Evaluation of the antitumor activity of gemcitabine (2\u2032,2\u2032-difluoro-2\u2032-deoxycytidine)","volume":"50","author":"Hertel","year":"1990","journal-title":"Cancer Res."},{"issue":"3","key":"10.1016\/j.ejmech.2025.118146_bib9","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/BF00194526","article-title":"Comparison of the antitumor activity of gemcitabine and ara-C in a panel of human breast, colon, lung and pancreatic xenograft models, Invest","volume":"14","author":"Merriman","year":"1996","journal-title":"N. Drugs"},{"issue":"3","key":"10.1016\/j.ejmech.2025.118146_bib10","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1586\/14737140.5.3.429","article-title":"Gemcitabine in metastatic breast cancer","volume":"5","author":"Heinemann","year":"2005","journal-title":"Exert. Rev. Anticanc."},{"issue":"2","key":"10.1016\/j.ejmech.2025.118146_bib11","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/sj.bjc.6603860","article-title":"Pharmacogenomics of gemcitabine: can genetic studies lead to tailor-made therapy?","volume":"97","author":"Ueno","year":"2007","journal-title":"Brit. J. Cancer"},{"key":"10.1016\/j.ejmech.2025.118146_bib12","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ejps.2016.08.021","article-title":"Recent advances in drug delivery strategies for improved therapeutic efficacy of gemcitabine","volume":"93","author":"Dubey","year":"2016","journal-title":"Eur. J. Pharmaceut. Sci."},{"issue":"22","key":"10.1016\/j.ejmech.2025.118146_bib13","first-page":"6110","article-title":"Action of 2\u2032,2\u2032-difluorodeoxycytidine on DNA synthesis","volume":"51","author":"Huang","year":"1991","journal-title":"Cancer Res."},{"issue":"4","key":"10.1016\/j.ejmech.2025.118146_bib14","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/0006-2952(93)90566-F","article-title":"2\u2032,2\u2032-Difluorodeoxycytidine (gemcitabine) incorporation into RNA and DNA of tumor cell lines","volume":"46","author":"Veerman","year":"1993","journal-title":"Biochem. Pharmacol."},{"issue":"2","key":"10.1016\/j.ejmech.2025.118146_bib15","first-page":"S7","article-title":"Preclinical, pharmacologic, and phase I studies of gemcitabine","volume":"24","author":"Storniolo","year":"1997","journal-title":"Semin. Oncol."},{"issue":"11","key":"10.1016\/j.ejmech.2025.118146_bib16","doi-asserted-by":"crossref","first-page":"3477","DOI":"10.1158\/1078-0432.CCR-07-4521","article-title":"Oral administration of gemcitabine in patients with refractory tumors: a clinical and pharmacologic study","volume":"14","author":"Veltkamp","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ejmech.2025.118146_bib17","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.drup.2015.10.002","article-title":"Gemcitabine resistance in pancreatic ductal adenocarcinoma, drug","volume":"23","author":"Binenbaum","year":"2015","journal-title":"Resist. Updates."},{"issue":"11","key":"10.1016\/j.ejmech.2025.118146_bib18","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.1158\/1078-0432.CCR-07-4885","article-title":"Modulation of gemcitabine (2\u2032,2\u2032-Difluoro-2\u2032-Deoxycytidine) pharmacokinetics, metabolism, and bioavailability in mice by 3,4,5,6-Tetrahydrouridine","volume":"14","author":"Beumer","year":"2008","journal-title":"Clin. Cancer Res."},{"issue":"5","key":"10.1016\/j.ejmech.2025.118146_bib19","doi-asserted-by":"crossref","first-page":"v7","DOI":"10.1093\/annonc\/mdj941","article-title":"Cellular pharmacology of gemcitabine","volume":"17","author":"Mini","year":"2006","journal-title":"Ann. Oncol."},{"issue":"19","key":"10.1016\/j.ejmech.2025.118146_bib20","first-page":"4349","article-title":"Functional nucleoside transporters are required for gemcitabine influx and manifestation of toxicity in cancer cell lines","volume":"58","author":"Mackey","year":"1998","journal-title":"Cancer Res."},{"key":"10.1016\/j.ejmech.2025.118146_bib21","first-page":"7217","article-title":"Mechanisms of uptake and resistance to troxacitabine, a novel deoxycytidine nucleoside analogue, in human leukemic and solid tumor cell lines","volume":"61","author":"Gourdeau","year":"2001","journal-title":"Cancer Res."},{"issue":"15","key":"10.1016\/j.ejmech.2025.118146_bib22","first-page":"4138","article-title":"Development and molecular characterization of a 2\u2032,2\u2032-difluorodeoxycytidine-resistant variant of the human ovarian carcinoma cell line A2780","volume":"54","author":"Ruiz van Haperen","year":"1994","journal-title":"Cancer Res."},{"issue":"6","key":"10.1016\/j.ejmech.2025.118146_bib23","first-page":"371","article-title":"Pretreatment deoxycytidine kinase levels predict in vivo gemcitabine sensitivity","volume":"1","author":"Kroep","year":"2002","journal-title":"Mol. Cancer Therapeut."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118146_bib24","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1471-2210-4-8","article-title":"Resistance to gemcitabine in a human follicular lymphoma cell line is due to partial deletion of the deoxycytidine kinase gene","volume":"4","author":"Galmarini","year":"2004","journal-title":"BMC Pharmacol."},{"key":"10.1016\/j.ejmech.2025.118146_bib25","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.ejmech.2017.08.010","article-title":"Prodrug strategy for cancer cell-specific targeting: a recent overview","volume":"139","author":"Zhang","year":"2017","journal-title":"Eur. J. Med. Chem."},{"issue":"3","key":"10.1016\/j.ejmech.2025.118146_bib26","doi-asserted-by":"crossref","first-page":"466","DOI":"10.3390\/genes13030466","article-title":"Recent development of prodrugs of gemcitabine","volume":"13","author":"Pandit","year":"2022","journal-title":"Genes"},{"issue":"33","key":"10.1016\/j.ejmech.2025.118146_bib27","doi-asserted-by":"crossref","first-page":"5562","DOI":"10.2174\/0929867326666190816230650","article-title":"Small molecular gemcitabine prodrugs for cancer therapy","volume":"27","author":"Miao","year":"2020","journal-title":"Curr. Med. Chem."},{"issue":"22","key":"10.1016\/j.ejmech.2025.118146_bib28","doi-asserted-by":"crossref","first-page":"6958","DOI":"10.1021\/jm901181h","article-title":"Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine","volume":"52","author":"Bender","year":"2009","journal-title":"J. Med. Chem."},{"issue":"3","key":"10.1016\/j.ejmech.2025.118146_bib29","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1007\/s10637-009-9377-7","article-title":"Antiproliferative activity, mechanism of action and oral antitumor activity of CP-4126, a fatty acid derivative of gemcitabine, in in vitro and in vivo tumor models","volume":"29","author":"Bergman","year":"2010","journal-title":"Invest. N. Drugs"},{"issue":"4","key":"10.1016\/j.ejmech.2025.118146_bib30","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1007\/s10637-013-9925-z","article-title":"Phase I study of oral CP-4126, a gemcitabine derivative, in patients with advanced solid tumors","volume":"31","author":"Stuurman","year":"2013","journal-title":"Invest. N. Drugs"},{"issue":"4","key":"10.1016\/j.ejmech.2025.118146_bib31","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1021\/jm401853a","article-title":"Application of ProTide technology to gemcitabine: a successful approach to overcome the key cancer resistance mechanisms leads to a new agent (NUC-1031) in clinical development","volume":"57","author":"Slusarczyk","year":"2014","journal-title":"J. Med. Chem."},{"issue":"4","key":"10.1016\/j.ejmech.2025.118146_bib32","doi-asserted-by":"crossref","first-page":"S272","DOI":"10.1016\/j.annonc.2020.08.058","article-title":"80TiP global phase III study of NUC-1031 plus cisplatin vs gemcitabine plus cisplatin for first-line treatment of patients with advanced biliary tract cancer (NuTide:121)","volume":"31","author":"Knox","year":"2020","journal-title":"Ann. Oncol."},{"issue":"5","key":"10.1016\/j.ejmech.2025.118146_bib33","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/0006-2952(91)90284-C","article-title":"High levels of expression of the NAD(P)H:quinone oxidoreductase (NQO1) gene in tumor cells compared to normal cells of the same origin","volume":"42","author":"Cresteil","year":"1991","journal-title":"Biochem. Pharmacol."},{"issue":"5","key":"10.1016\/j.ejmech.2025.118146_bib34","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1124\/mol.65.5.1238","article-title":"NAD(P)H:Quinone oxidoreductase 1: role as a superoxide scavenger","volume":"65","author":"Siegel","year":"2004","journal-title":"Mol. Pharm."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118146_bib35","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1756-9966-33-14","article-title":"Clinical implications of high NQO1 expression in breast cancers","volume":"33","author":"Yang","year":"2014","journal-title":"J. Exp. Clin. Cancer Res."},{"issue":"7","key":"10.1016\/j.ejmech.2025.118146_bib36","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/bjc.1997.485","article-title":"DT-diaphorase and cytochrome B5 reductase in human lung and breast tumours","volume":"76","author":"Mar\u00edn","year":"1997","journal-title":"Br. J. Cancer"},{"issue":"6","key":"10.1016\/j.ejmech.2025.118146_bib37","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.3892\/or.2014.3494","article-title":"NAD(P)H:quinone oxidoreductase-1 overexpression predicts poor prognosis in small cell lung cancer","volume":"32","author":"Cui","year":"2014","journal-title":"Oncol. Rep."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118146_bib38","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1186\/s12885-015-1227-8","article-title":"NQO1 protein expression predicts poor prognosis of non-small cell lung cancers","volume":"15","author":"Li","year":"2015","journal-title":"BMC Cancer"},{"issue":"28","key":"10.1016\/j.ejmech.2025.118146_bib39","doi-asserted-by":"crossref","first-page":"11832","DOI":"10.1073\/pnas.0702176104","article-title":"An NQO1- and PARP-1-mediated cell death pathway induced in non-small-cell lung cancer cells by beta-lapachone","volume":"104","author":"Bey","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"issue":"4","key":"10.1016\/j.ejmech.2025.118146_bib40","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/mc.20107","article-title":"Targeting NAD(P)H:quinone oxidoreductase (NQO1) in pancreatic cancer","volume":"43","author":"Lewis","year":"2005","journal-title":"Mol. Carcinog."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118146_bib41","doi-asserted-by":"crossref","first-page":"102","DOI":"10.4161\/cbt.4.1.1382","article-title":"Efficacy of beta-lapachone in pancreatic cancer treatment: exploiting the novel, therapeutic target NQO1","volume":"4","author":"Ough","year":"2005","journal-title":"Cancer Biol. Ther."},{"key":"10.1016\/j.ejmech.2025.118146_bib42","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.jconrel.2022.07.033","article-title":"Albumin binding revitalizes NQO1 bioactivatable drugs as novel therapeutics for pancreatic cancer","volume":"349","author":"Dou","year":"2022","journal-title":"J. Control. Release"},{"issue":"2","key":"10.1016\/j.ejmech.2025.118146_bib43","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.yexmp.2013.12.008","article-title":"Significance of NQO1 overexpression for prognostic evaluation of gastric adenocarcinoma","volume":"96","author":"Lin","year":"2014","journal-title":"Exp. Mol. Pathol."},{"issue":"5","key":"10.1016\/j.ejmech.2025.118146_bib44","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1124\/mol.65.5.1238","article-title":"NAD(P)H: quinone oxidoreductase 1: role as a superoxide scavenger","volume":"65","author":"Siegel","year":"2004","journal-title":"Mol. Pharmacol."},{"issue":"16","key":"10.1016\/j.ejmech.2025.118146_bib45","doi-asserted-by":"crossref","first-page":"6983","DOI":"10.1021\/acs.jmedchem.8b00124","article-title":"NAD(P)H:Quinone oxidoreductase 1 (NQO1) as a therapeutic and diagnostic target in cancer","volume":"61","author":"Zhang","year":"2018","journal-title":"J. Med. Chem."},{"issue":"40","key":"10.1016\/j.ejmech.2025.118146_bib46","doi-asserted-by":"crossref","first-page":"8014","DOI":"10.1021\/bi300760u","article-title":"Human NAD(P)H:Quinone oxidoreductase type I (hNQO1) activation of quinone propionic acid trigger groups","volume":"51","author":"Mendoza","year":"2012","journal-title":"Biochemistry"},{"issue":"1","key":"10.1016\/j.ejmech.2025.118146_bib47","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1021\/ja309346f","article-title":"Profluorogenic reductase substrate for rapid, selective, and sensitive visualization and detection of human cancer cells that overexpress NQO1","volume":"135","author":"Silvers","year":"2012","journal-title":"J. Am. Chem. Soc."},{"issue":"21","key":"10.1016\/j.ejmech.2025.118146_bib48","doi-asserted-by":"crossref","first-page":"7575","DOI":"10.1021\/ja5030707","article-title":"Detection and cellular imaging of human cancer enzyme using a turn-on, wavelength-shiftable, self-immolative profluorophore","volume":"136","author":"Hettiarachchi","year":"2014","journal-title":"J. Am. Chem. Soc."},{"issue":"12","key":"10.1016\/j.ejmech.2025.118146_bib49","doi-asserted-by":"crossref","first-page":"3635","DOI":"10.1021\/acs.orglett.8b01409","article-title":"An NAD(P)H: quinone oxidoreductase 1 responsive and self-immolative prodrug of 5-fluorouracil for safe and effective cancer therapy","volume":"20","author":"Zhang","year":"2018","journal-title":"Org. Lett."},{"key":"10.1016\/j.ejmech.2025.118146_bib50","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.ejmech.2017.03.055","article-title":"Design, synthesis, and biological evaluation of NAD(P)H: quinone oxidoreductase (NQO1)-targeted oridonin prodrugs possessing indolequinone moiety for hypoxia-selective activation","volume":"132","author":"Xu","year":"2017","journal-title":"Eur. J. Med. Chem."},{"issue":"12","key":"10.1016\/j.ejmech.2025.118146_bib51","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1021\/acsmedchemlett.8b00404","article-title":"NQO1-Selective activated prodrug of triptolide: synthesis and antihepatocellular carcinoma activity evaluation, ACS","volume":"9","author":"Liu","year":"2018","journal-title":"Med. Chem. Lett."},{"issue":"10","key":"10.1016\/j.ejmech.2025.118146_bib52","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1021\/acsmedchemlett.9b00161","article-title":"A bioreductive prodrug of cucurbitacin B significantly inhibits tumor growth in the 4T1 xenograft mice model","volume":"10","author":"Suebsakwong","year":"2019","journal-title":"ACS Med. Chem. Lett."},{"issue":"24","key":"10.1016\/j.ejmech.2025.118146_bib53","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2020.115821","article-title":"Synthesis and biological evaluation of NQO1-activated prodrugs of podophyllotoxin as antitumor agents","volume":"28","author":"Qu","year":"2020","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118146_bib54","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2020.104200","article-title":"NQO1-selective activated prodrugs of combretastatin A-4: synthesis and biological evaluation","volume":"103","author":"Zhang","year":"2020","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2025.118146_bib55","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2022.114575","article-title":"Design and synthesis of NAD(P)H: quinone oxidoreductase (NQO1)-activated prodrugs of 23-hydroxybetulinic acid with enhanced antitumor properties","volume":"240","author":"Zhu","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118146_bib56","doi-asserted-by":"crossref","DOI":"10.1002\/smll.202410861","article-title":"NQO1\u2010Responsive prodrug for in cellulo release of cytochalasin B as cancer cell\u2010targeted migrastatic","author":"Kagho","year":"2025","journal-title":"Small"},{"key":"10.1016\/j.ejmech.2025.118146_bib57","article-title":"Discovery and mechanistic elucidation of NQO1\u2010Bioactivatable small molecules that overcome resistance to degraders","volume":"63","author":"Barbosa","year":"2024","journal-title":"Angew. Chem. Int. Ed."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118146_bib58","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1074\/jbc.M105324200","article-title":"Mutation of residue 33 of human equilibrative nucleoside transporters 1 and 2 alters sensitivity to inhibition of transport by dilazep and dipyridamole","volume":"277","author":"Visser","year":"2002","journal-title":"J. Biol. Chem."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118146_bib59","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0006-2952(78)90256-3","article-title":"Analysis of cytidine deaminase and tetrahydrouridine interaction by use of ligand techniques","volume":"27","author":"Stoller","year":"1978","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ejmech.2025.118146_bib60","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2024.103130","article-title":"In pursuit of feedback activation: new insights into redox-responsive hydropersulfide prodrug combating oxidative stress","volume":"72","author":"Xu","year":"2024","journal-title":"Redox Biol."},{"issue":"21","key":"10.1016\/j.ejmech.2025.118146_bib61","article-title":"Combination therapy of lox inhibitor and stimuli\u2010responsive drug for mechanochemically synergistic breast cancer treatment","volume":"12","author":"Zhu","year":"2023","journal-title":"Adv. Healthc. Meter."},{"issue":"22","key":"10.1016\/j.ejmech.2025.118146_bib62","doi-asserted-by":"crossref","first-page":"5787","DOI":"10.1016\/j.bmc.2016.09.033","article-title":"Discovery of a novel chimeric ubenimex\u2013gemcitabine with potent oral antitumor activity","volume":"24","author":"Jiang","year":"2016","journal-title":"Bioorg. Med. Chem."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425009110?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425009110?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T22:12:46Z","timestamp":1772835166000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523425009110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":62,"alternative-id":["S0223523425009110"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.118146","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Design, synthesis, and anti-cancer evaluation of NQO1-responsive prodrug of gemcitabine","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.118146","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118146"}}