{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:25:07Z","timestamp":1790807107913,"version":"4.1.0"},"reference-count":74,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T00:00:00Z","timestamp":1692144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004569","name":"Ministerstwo Edukacji i Nauki","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004569","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014418","name":"Instytut Biologii Doswiadczalnej im. M. Nenckiego PAN","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014418","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001870","name":"Fundacja na rzecz Nauki Polskiej","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001870","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004421","name":"Politechnika Warszawska","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004421","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2023,11]]},"DOI":"10.1016\/j.bioorg.2023.106784","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T19:47:40Z","timestamp":1692820060000},"page":"106784","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"special_numbering":"C","title":["Development of 5-fluorouracil-dichloroacetate mutual prodrugs as anticancer agents"],"prefix":"10.1016","volume":"140","author":[{"given":"Ewa","family":"Mironiuk-Puchalska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olena","family":"Karatsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"\u017buchowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Wr\u00f3blewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Borys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilya","family":"Lehka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jolanta","family":"R\u0119dowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariola","family":"Koszytkowska-Stawi\u0144ska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bioorg.2023.106784_b0005","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/179663a0","article-title":"Fluorinated pyrimidines, a new class of tumor-inhibitory compounds","volume":"179","author":"Heidelberger","year":"1957","journal-title":"Nature"},{"key":"10.1016\/j.bioorg.2023.106784_b0010","unstructured":"WHO Model List of Essential Medicines on the Web Sites: http:\/\/www.who.int."},{"key":"10.1016\/j.bioorg.2023.106784_b0015","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nrc1074","article-title":"5-Fluorouracil: mechanisms of action and clinical strategies","volume":"3","author":"Longley","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.bioorg.2023.106784_b0020","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/bjc.1994.259","article-title":"Continuous 5-fluorouracil in the treatment of breast cancer","volume":"70","author":"Cameron","year":"1994","journal-title":"Br. J. Cancer"},{"issue":"1","key":"10.1016\/j.bioorg.2023.106784_b0025","doi-asserted-by":"crossref","DOI":"10.1186\/s12935-021-02088-3","article-title":"CircFBXL5 promotes the 5-FU resistance of breast cancer via modulating miR-216b\/HMGA2 axis","volume":"21","author":"Zhu","year":"2021","journal-title":"Cancer Cell Int."},{"key":"10.1016\/j.bioorg.2023.106784_b0030","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1002\/1097-0142(19930515)71:10<2953::AID-CNCR2820711011>3.0.CO;2-J","article-title":"Cisplatin, 5-fluorouracil, and etoposide for advanced non-small cell lung cancer","volume":"71","author":"Lynch","year":"1993","journal-title":"Cancer"},{"key":"10.1016\/j.bioorg.2023.106784_b0035","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/S1053-4296(97)80026-4","article-title":"Radiation therapy with 5-fluorouracil in head and neck cancer","volume":"7","author":"Fu","year":"1997","journal-title":"Semin. Radiat. Oncol."},{"key":"10.1016\/j.bioorg.2023.106784_b0040","doi-asserted-by":"crossref","first-page":"761","DOI":"10.3389\/fonc.2020.00761","article-title":"Comparison of carboplatin with 5-fluorouracil vs. cisplatin as concomitant chemoradiotherapy for locally advanced head and neck squamous cell carcinoma","volume":"10","author":"Hanemaaijer","year":"2020","journal-title":"Front. Oncol."},{"key":"10.1016\/j.bioorg.2023.106784_b0045","doi-asserted-by":"crossref","first-page":"192","DOI":"10.36849\/JDD.5518","article-title":"Intralesional 5-fluorouracil for treatment of non-melanoma skin cancer: a systematic review","volume":"20","author":"Maghfour","year":"2021","journal-title":"J. Drug. Dermatol."},{"issue":"1\u20132","key":"10.1016\/j.bioorg.2023.106784_b0050","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.ijpharm.2017.07.055","article-title":"Development of biomedical 5-fluorouracil nanoplatforms for colon cancer chemotherapy: Influence of process and formulation parameters","volume":"530","author":"Pretel","year":"2017","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.bioorg.2023.106784_b0055","doi-asserted-by":"crossref","first-page":"284","DOI":"10.7150\/ijbs.10248","article-title":"5-Fluorouracil chemotherapy of gastric cancer generates residual cells with properties of cancer cells","volume":"11","author":"Xu","year":"2015","journal-title":"Int. J. Biol. Sci."},{"key":"10.1016\/j.bioorg.2023.106784_b0060","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s40170-020-00218-5","article-title":"Modulating pyrimidine ribonucleotide levels for the treatment of cancer","volume":"8","author":"Mollick","year":"2020","journal-title":"Cancer Metab."},{"key":"10.1016\/j.bioorg.2023.106784_b0065","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1159\/000443984","article-title":"New perspectives in the treatment of advanced gastric cancer: S-1 as a novel oral 5-FU therapy in combination with cisplatin","volume":"62","author":"Mahlberg","year":"2017","journal-title":"Chemotherapy"},{"key":"10.1016\/j.bioorg.2023.106784_b0070","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1634\/theoncologist.7-4-288","article-title":"Clinical studies of three oral prodrugs of 5-fluorouracil (Capecitabine, UFT, S-1): a review","volume":"7","author":"Malet-Martino","year":"2002","journal-title":"Oncologist"},{"key":"10.1016\/j.bioorg.2023.106784_b0075","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1517\/13543776.2015.1056736","article-title":"5-Fluorouracil derivatives: a patent review (2012\u20132014)","volume":"25","author":"Carrillo","year":"2015","journal-title":"Expert Opin. Ther. Patents"},{"key":"10.1016\/j.bioorg.2023.106784_b0080","doi-asserted-by":"crossref","first-page":"4655","DOI":"10.21873\/anticanres.14464","article-title":"Current status of therapeutic drug monitoring of 5-fluorouracil prodrugs","volume":"40","author":"Hashimoto","year":"2020","journal-title":"Anticancer Res"},{"key":"10.1016\/j.bioorg.2023.106784_b0085","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.ejps.2010.09.014","article-title":"Codrugs: An efficient approach for drug optimization","volume":"41","author":"Das","year":"2010","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.bioorg.2023.106784_b0090","doi-asserted-by":"crossref","unstructured":"S. Dhaneshwar, P. P. Joshi, S. Pawar, Codrugs: Optimum use through prodrugs, in: K. Shah, D. N. Chauhan, N. S. Chauhan, P. Mishra (Eds.), Recent Advancement in Prodrugs, CRC Press, 1st ed., Boca Raton, 2020.","DOI":"10.1201\/9780429328275"},{"key":"10.1016\/j.bioorg.2023.106784_b0095","doi-asserted-by":"crossref","first-page":"3496","DOI":"10.1002\/cmdc.202100473","article-title":"Mutual prodrugs of 5-fluorouracil: From a classic chemotherapeutic agent to novel potential anticancer drugs","volume":"16","author":"Ciaffaglione","year":"2021","journal-title":"ChemMedChem"},{"key":"10.1016\/j.bioorg.2023.106784_b0100","doi-asserted-by":"crossref","first-page":"9083","DOI":"10.1021\/jo971076p","article-title":"Synthesis and reactivity of 5-fluorouracil\/cytabine mutual prodrug","volume":"62","author":"Menger","year":"1997","journal-title":"J. Org. Chem."},{"key":"10.1016\/j.bioorg.2023.106784_b0105","doi-asserted-by":"crossref","first-page":"4450","DOI":"10.1021\/acs.jmedchem.0c00897","article-title":"Targetin colorectal cancer with conjugates of a glucose transporter inhibitor an 5-fluorouracil","volume":"64","author":"Chang","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106784_b0110","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.ejmech.2017.11.074","article-title":"Synthesis and biological characterization of ubenimex-fluorouracil conjugates for anti-cancer therapy","volume":"143","author":"Jiang","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106784_b0115","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1080\/03639040601134108","article-title":"A novel chemical delivery system comprising an ocular sustained release formulation of a 3\u03b1, 17\u03b1, 21-trihydroxy-5\u03b2-pregnan-20-one-bis-5-flourouracil codrug","volume":"33","author":"Howard-Sparks","year":"2007","journal-title":"Drug Dev. Ind. Pharm."},{"key":"10.1016\/j.bioorg.2023.106784_b0120","doi-asserted-by":"crossref","first-page":"4543","DOI":"10.1021\/acs.jmedchem.9b00128","article-title":"Fuplatin: an efficient and low-toxic dual-prodrug","volume":"62","author":"Zhang","year":"2019","journal-title":"J. Med. Chem."},{"issue":"2","key":"10.1016\/j.bioorg.2023.106784_b0125","first-page":"617","article-title":"Dichloroacetate and cancer. New home for an orphan drug","volume":"1846","author":"Kankotia","year":"2014","journal-title":"BBA"},{"key":"10.1016\/j.bioorg.2023.106784_b0130","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.ccr.2006.10.020","article-title":"A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth","volume":"11","author":"Bonnet","year":"2007","journal-title":"Cancer Cell"},{"key":"10.1016\/j.bioorg.2023.106784_b0135","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.ygyno.2008.01.038","article-title":"Dichloroacetate induces apoptosis in endometrial cancer","volume":"109","author":"Wong","year":"2008","journal-title":"Gynecol. Oncol."},{"key":"10.1016\/j.bioorg.2023.106784_b0140","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.pharmthera.2016.10.018","article-title":"Therapeutic applications of dichloroacetate and the role of glutathione transferase zeta-1","volume":"170","author":"James","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.bioorg.2023.106784_b0145","article-title":"Effects of dichloroacetate as single agent or in combination with GW6471 and metformin in paraganglioma cells","volume":"8","author":"Florio","year":"2018","journal-title":"Nature. Scient. Rep."},{"key":"10.1016\/j.bioorg.2023.106784_b0150","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1016\/j.chempr.2018.08.002","article-title":"Overcoming drug resistance by targeting cancer bioenergetics with an activatable prodrug","volume":"4","author":"Sharma","year":"2018","journal-title":"Chem"},{"key":"10.1016\/j.bioorg.2023.106784_b0155","article-title":"Synergistic antitumor effect of dichloroacetate in combination with 5-fluorouracil in colorectal cancer","author":"Tong","year":"2011","journal-title":"J. Biomed. Biotechnol."},{"key":"10.1016\/j.bioorg.2023.106784_b0160","doi-asserted-by":"crossref","first-page":"8760","DOI":"10.1021\/acs.jmedchem.9b00644","article-title":"Natural product Albiziabioside a conjugated with pyruvate dehydrogenase kinase inhibitor dichloroacetate to induce apoptosis-ferroptosis-M2-TAMs polarization for combined cancer therapy","volume":"62","author":"Wei","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2023.106784_b0165","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/cbdd.13638","article-title":"Design, synthesis, antimicrobial, and DNA gyrase inhibitory properties of fluoroquinolone\u2013dichloroacetic acid hybrids","volume":"95","author":"Seliem","year":"2020","journal-title":"Chem. Biol. Drug Des."},{"key":"10.1016\/j.bioorg.2023.106784_b0170","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1002\/bit.23071","article-title":"Development of a dichloroacetic acid-hemoglobin conjugate as a potential targeted anti-cancer therapeutic","volume":"108","author":"Zhang","year":"2011","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.bioorg.2023.106784_b0175","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1039\/C7MD00248C","article-title":"Mitochondria-targeted betulinic and ursolic acid derivatives: synthesis and anticancer activity","volume":"8","author":"Nedopekina","year":"2017","journal-title":"Med. Chem. Comm."},{"key":"10.1016\/j.bioorg.2023.106784_b0180","doi-asserted-by":"crossref","first-page":"7762","DOI":"10.1038\/srep07762","article-title":"A potent tumoricidal co-drug \u2018Bet-CA\u2019 - an ester derivative of betulinic acid and dichloroacetateselectively and synergistically kills cancer cells","volume":"5","author":"Saha","year":"2015","journal-title":"Sci. Rep."},{"key":"10.1016\/j.bioorg.2023.106784_b0185","doi-asserted-by":"crossref","first-page":"52822","DOI":"10.1039\/C7RA10229A","article-title":"Polarity-extended quantitative analysis of bear bile and its analogues using serially coupled reversed phase-hydrophilic interaction liquid chromatography-tailored multiple reaction monitoring","volume":"7","author":"Song","year":"2017","journal-title":"RSC Adv."},{"key":"10.1016\/j.bioorg.2023.106784_b0190","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.2147\/IJN.S154361","article-title":"A facile doxorubicin-dichloroacetate conjugate nanomedicine with high drug loading for safe drug delivery","volume":"13","author":"Yang","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"10.1016\/j.bioorg.2023.106784_b0195","doi-asserted-by":"crossref","first-page":"22199","DOI":"10.1073\/pnas.0912276106","article-title":"Mitaplatin, a potent fusion of cisplatin and the orphan drug dichloroacetate","volume":"106","author":"Dhar","year":"2009","journal-title":"PNAS"},{"key":"10.1016\/j.bioorg.2023.106784_b0200","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jinorgbio.2015.12.003","article-title":"Potentiation of mitochondrial dysfunction in tumor cells by conjugates of metabolic modulator dichloroacetate with a Pt(IV) derivative of oxaliplatin","volume":"156","author":"Zajac","year":"2016","journal-title":"J. Inorg. Biochem."},{"key":"10.1016\/j.bioorg.2023.106784_b0205","series-title":"Handbook of Pharmaceutical Salts: Properties, Selection and Use","author":"Stahl","year":"2002"},{"key":"10.1016\/j.bioorg.2023.106784_b0210","unstructured":"e.g. mycophenolate mofeti (CellCept\u00ae Roche), digoxin (Lanoxin\u00ae Aspen Pharma), rifaximin (Rifxan\u00ae Salix Pharmaceuticals)."},{"key":"10.1016\/j.bioorg.2023.106784_b0215","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1080\/02652040110081389","article-title":"Gastric resistant microbeads of metal ion cross-linked carboxymethyl guar gum for oral drug delivery","volume":"19","author":"Reddy","year":"2002","journal-title":"J. Microencapsul."},{"key":"10.1016\/j.bioorg.2023.106784_b0220","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.3390\/polym14102010","article-title":"5-Fluorouracil loaded folic acid fabricated chitosan nanoparticles for site targeted drug delivery cargo","volume":"14","author":"Ullah","year":"2022","journal-title":"Polymers"},{"key":"10.1016\/j.bioorg.2023.106784_b0225","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1021\/acsnano.2c11188","article-title":"Synthetic lignin-derived therapeutic nano reagent as intestinal pH-sensitive drug carriers capable of bypassing the gastric acid environment for colitis treatment","volume":"17","author":"Zhao","year":"2023","journal-title":"ACS Nano"},{"key":"10.1016\/j.bioorg.2023.106784_b0230","doi-asserted-by":"crossref","first-page":"524","DOI":"10.3389\/fphar.2020.00524","article-title":"Advances in oral drug delivery for regional targeting in the gastrointestinal tract - influence of physiological, pathophysiological and pharmaceutical factors","volume":"11","author":"Hua","year":"2020","journal-title":"Front. Pharm."},{"key":"10.1016\/j.bioorg.2023.106784_b0235","unstructured":"Half-life is defined as the time it takes for the drug concentration to be reduced in half."},{"issue":"1","key":"10.1016\/j.bioorg.2023.106784_b0240","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0378-5173(85)90143-7","article-title":"Prodrugs of 5-fluorouracil. IV. Hydrolysis kinetics, bioactivation and physicochemical properties of various N-acyloxymethyl derivatives of 5-fluorouracil","volume":"24","author":"Buur","year":"1985","journal-title":"Int. J. Pharm."},{"issue":"1","key":"10.1016\/j.bioorg.2023.106784_b0245","doi-asserted-by":"crossref","DOI":"10.1186\/s12935-019-0733-1","article-title":"The effect of 2D and 3D cell cultures on treatment response, EMT profile and stem cell features in head and neck cancer","volume":"19","author":"Melissaridou","year":"2019","journal-title":"Cancer Cell Int"},{"issue":"1","key":"10.1016\/j.bioorg.2023.106784_b0250","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/bit.26845","article-title":"3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs","volume":"116","author":"Nunes","year":"2019","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.bioorg.2023.106784_b0255","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/j.biotechadv.2016.11.002","article-title":"3D tumor spheroids: an overview on the tools and techniques used for their analysis","volume":"34","author":"Costa","year":"2016","journal-title":"Biotechnol. Adv."},{"key":"10.1016\/j.bioorg.2023.106784_b0260","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2022.840674","article-title":"Organ-On-A-Chip: a survey of technical results and problems","volume":"10","author":"Danku","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"10.1016\/j.bioorg.2023.106784_b0265","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1158\/1078-0432.CCR-05-2518","article-title":"Genetic Alterations in Signaling Pathways in Melanoma","volume":"12","author":"Haluska","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.bioorg.2023.106784_b0270","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.ceb.2011.12.004","article-title":"Directed cell invasion and migration during metastasis","volume":"24","author":"Bravo-Cordero","year":"2012","journal-title":"Curr. Opin. Cell Biol."},{"key":"10.1016\/j.bioorg.2023.106784_b0275","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/sj.cdd.4401002","article-title":"Apoptosis induced by disruption of the actin cytoskeleton is mediated via activation of CD95 (Fas\/APO-1)","volume":"9","author":"Kulms","year":"2002","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.bioorg.2023.106784_b0280","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1078\/0171-9335-00282","article-title":"Partial cleavage of A-type lamins concurs with their total disintegration from the nuclear lamina during apoptosis","volume":"81","author":"Broers","year":"2002","journal-title":"Eur. J. Cell Biol."},{"key":"10.1016\/j.bioorg.2023.106784_b0285","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.addr.2010.11.001","article-title":"Focal adhesion kinase and Its signaling pathways in cell migration and angiogenesis","volume":"63","author":"Zhao","year":"2011","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.bioorg.2023.106784_b0290","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.snb.2018.08.037","article-title":"Different action of nanoencapsulated meso-tetraphenylporphyrin in breast spheroid co-culture and mono-culture under microfluidic conditions","volume":"275","author":"Zuchowska","year":"2018","journal-title":"Sens. Actuators B Chem."},{"key":"10.1016\/j.bioorg.2023.106784_b0295","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/s41578-021-00313-z","article-title":"Organ chips, organoids and the animal testing conundrum","volume":"6","author":"Horejs","year":"2021","journal-title":"Nat. Rev. Mat."},{"key":"10.1016\/j.bioorg.2023.106784_b0300","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.jacbts.2020.03.010","article-title":"Limitations of animal studies for predicting toxicity in clinical trials","volume":"5","author":"Van Norman","year":"2020","journal-title":"JACC Basic Transl. Sci."},{"key":"10.1016\/j.bioorg.2023.106784_b0305","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1016\/j.apsb.2022.02.002","article-title":"Why 90% of clinical drug development fails and how to improve it?","volume":"2","author":"Sun","year":"2022","journal-title":"Acta. Pharm. Sci. B"},{"key":"10.1016\/j.bioorg.2023.106784_b0310","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41551-019-0498-9","article-title":"Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips","volume":"4","author":"Herland","year":"2020","journal-title":"Nat Biomed. Eng."},{"key":"10.1016\/j.bioorg.2023.106784_b0315","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.662232","article-title":"New Weapons in the Fight Against Breast Cancer?","volume":"12","author":"Martorana","year":"2021","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.bioorg.2023.106784_b0320","first-page":"101","article-title":"Maximising the potential of AKT inhibitors as anti-cancer treatments Pharmacol","volume":"172","author":"Brown","year":"2017","journal-title":"Ther."},{"key":"10.1016\/j.bioorg.2023.106784_b0325","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.maturitas.2015.01.015","article-title":"PARP inhibitors: a new era of targeted therapy","volume":"81","author":"Tangutoori","year":"2015","journal-title":"Maturitas"},{"key":"10.1016\/j.bioorg.2023.106784_b0330","unstructured":"e.g. Olaparib (AZ 2281, KU59436) AstraZeneca: breast cancer, ovarian cancer, melanoma; Iniparib (BSI 201,BSI 401), Sanofi\/BiPar Sciences: breast cancer, non-small cell lung cancer."},{"key":"10.1016\/j.bioorg.2023.106784_b0335","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2023.106425","article-title":"Recent development of multi-target VEGFR-2 inhibitors for the cancer therapy","volume":"133","author":"Liu","year":"2023","journal-title":"Bioorg. Chem."},{"issue":"11","key":"10.1016\/j.bioorg.2023.106784_b0340","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.3390\/molecules25112666","article-title":"Research progress of small molecule VEGFR\/c-Met inhibitors as anticancer agents (2016\u2013Present)","volume":"25","author":"Zhang","year":"2020","journal-title":"Molecules"},{"key":"10.1016\/j.bioorg.2023.106784_b0345","article-title":"Targeting integrin pathways: mechanisms and advances in therapy","volume":"2, 8(1):1","author":"Pang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.bioorg.2023.106784_b0350","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41573-021-00284-4","article-title":"Emerging therapeutic opportunities for integrin inhibitors","volume":"21","author":"Slack","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.bioorg.2023.106784_b0355","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s41392-021-00572-w","article-title":"Small molecules in targeted cancer therapy: advances, challenges, and future perspectives","volume":"6","author":"Zhong","year":"2021","journal-title":"Sig Transduct Target Ther"},{"key":"10.1016\/j.bioorg.2023.106784_b0360","series-title":"Purification of Laboratory Chemicals","author":"Armarego","year":"2009"},{"key":"10.1016\/j.bioorg.2023.106784_b0365","series-title":"Thin-Layer Chromatography, Revised and Expanded","author":"Fried","year":"1999"},{"key":"10.1016\/j.bioorg.2023.106784_b0370","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1109\/TCBB.2012.82","article-title":"QuickVina: Accelerating AutoDock Vina Using Gradient-Based Heuristics for Global Optimization","volume":"9","author":"Handoko","year":"2012","journal-title":"IEEE\/ACM Trans. Comput. Biol. Bioinf."}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206823004455?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206823004455?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T08:48:32Z","timestamp":1758617312000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0045206823004455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11]]},"references-count":74,"alternative-id":["S0045206823004455"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2023.106784","relation":{},"ISSN":["0045-2068"],"issn-type":[{"value":"0045-2068","type":"print"}],"subject":[],"published":{"date-parts":[[2023,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Development of 5-fluorouracil-dichloroacetate mutual prodrugs as anticancer agents","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2023.106784","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"106784"}}