{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T15:28:02Z","timestamp":1780414082053,"version":"3.54.1"},"reference-count":31,"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\/100016419","name":"Breast Cancer Research Foundation of Alabama","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016419","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic &amp; Medicinal Chemistry Letters"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.bmcl.2025.130349","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T06:37:09Z","timestamp":1753857429000},"page":"130349","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Discovery of a novel non-toxic analog of clofarabine for the treatment of triple\u2013negative breast cancer"],"prefix":"10.1016","volume":"128","author":[{"given":"Omar","family":"Moukha-Chafiq","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Boohaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry D.","family":"Bratton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina Fosso","family":"Yatchang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anish K.","family":"Vadukoot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarath","family":"Sarngadharan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Augelli-Szafran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"suppl 2","key":"10.1016\/j.bmcl.2025.130349_bb0005","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.3816\/CBC.2009.s.008","article-title":"Biology, metastatic patterns, and treatment of patients with triple-negative breast cancer","volume":"9","author":"Anders","year":"2009","journal-title":"Clin Breast Cancer"},{"issue":"10","key":"10.1016\/j.bmcl.2025.130349_bb0010","doi-asserted-by":"crossref","first-page":"5285","DOI":"10.21873\/anticanres.13722","article-title":"Triple-negative breast cancer: the progress of targeted therapies and future tendencies","volume":"39","author":"Damaskos","year":"2019","journal-title":"Anticancer Res"},{"key":"10.1016\/j.bmcl.2025.130349_bb0015","article-title":"Current landscape of personalized clinical treatments for triple-negative breast cancer","volume":"13","author":"Zhang","year":"2022","journal-title":"Front Pharmacol"},{"issue":"6","key":"10.1016\/j.bmcl.2025.130349_bb0020","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1080\/13543784.2022.2067527","article-title":"PARP inhibitors as single agents and in combination therapy: the most promising treatment strategies in clinical trials for BRCA-mutant ovarian and triple-negative breast cancers","volume":"31","author":"Luo","year":"2022","journal-title":"Expert Opin Investig Drugs"},{"issue":"1","key":"10.1016\/j.bmcl.2025.130349_bb0025","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s12916-019-1326-5","article-title":"Recent advances in triple negative breast cancer: the immunotherapy era","volume":"17","author":"Marra","year":"2019","journal-title":"BMC Med"},{"issue":"3","key":"10.1016\/j.bmcl.2025.130349_bb0030","doi-asserted-by":"crossref","first-page":"4439","DOI":"10.2217\/fon-2019-0468","article-title":"Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer","volume":"16","author":"Mavratzas","year":"2020","journal-title":"Future Oncol"},{"key":"10.1016\/j.bmcl.2025.130349_bb0035","first-page":"OF1","article-title":"FDA Approval Summary: pembrolizumab for neoadjuvant and adjuvant treatment of patients with high-risk early-stage triple negative breast cancer","author":"Shah","year":"2022","journal-title":"Clin Cancer Res"},{"issue":"14","key":"10.1016\/j.bmcl.2025.130349_bb0040","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1007\/s40265-022-01781-5","article-title":"Emerging targeted therapies for early breast cancer","volume":"82","author":"Schlam","year":"2022","journal-title":"Drugs"},{"issue":"1\u20132","key":"10.1016\/j.bmcl.2025.130349_bb0045","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1080\/15257770008033020","article-title":"Preclinical antitumor activity of 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine (Cl-F-Ara-A)","volume":"19","author":"Waud","year":"2000","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"10.1016\/j.bmcl.2025.130349_bb0050","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1038\/nrd2055","article-title":"Discovery and development of clofarabine: a nucleoside analogue for treating cancer","author":"Bonate","year":"2006","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.bmcl.2025.130349_bb0055","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1007\/s00432-017-2457-8","article-title":"Clinical pharmacology and clinical trials of ribonucleotide reductase inhibitors: is it a viable cancer therapy?","author":"Mannargudi","year":"2017","journal-title":"J Cancer Res Clin Oncol"},{"issue":"7","key":"10.1016\/j.bmcl.2025.130349_bb0060","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1182\/blood-2003-03-0925","article-title":"Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia","volume":"102","author":"Kantarjian","year":"2003","journal-title":"Blood"},{"issue":"1\u20132","key":"10.1016\/j.bmcl.2025.130349_bb0065","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0304-3835(98)00131-1","article-title":"Analysis of DNA methylation of the 5\u2032 region of the deoxycytidine kinase gene in CCRF-CEM-sensitive and cladribine (CdA)- and 2-chloro-2\u2032-arabino-fluoro-2\u2019-deoxyadenosine (CAFdA)-resistant cells","volume":"130","author":"Leegwater","year":"1998","journal-title":"Cancer Lett"},{"issue":"9","key":"10.1016\/j.bmcl.2025.130349_bb0070","first-page":"2438","article-title":"Biochemical pharmacology and resistance to 2-chloro-2\u2032-arabinofluoro-2\u2032-deoxyadenosine, a novel analogue of cladribine in human leukemic cells","volume":"5","author":"Lotfi","year":"1999","journal-title":"Clin Cancer Res"},{"issue":"2","key":"10.1016\/j.bmcl.2025.130349_bb0075","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0006-2952(02)01484-3","article-title":"Down-regulation of deoxycytidine kinase in human leukemic cell lines resistant to cladribine and clofarabine and increased ribonucleotide reductase activity contributes to fludarabine resistance","volume":"65","author":"M\u00e5nsson","year":"2003","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.bmcl.2025.130349_bb0080","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/j.bcp.2009.06.094","article-title":"Mechanisms of anti-cancer action and pharmacology of clofarabine","author":"Zhenchuk","year":"2009","journal-title":"Biochem Pharmacol"},{"issue":"4","key":"10.1016\/j.bmcl.2025.130349_bb0085","doi-asserted-by":"crossref","first-page":"471","DOI":"10.15171\/apb.2015.064","article-title":"Clofarabine has apoptotic effect on T47D breast cancer cell line via P53R2 gene expression","volume":"5","author":"Rahmati-Yamchi","year":"2015","journal-title":"Adv Pharm Bull"},{"key":"10.1016\/j.bmcl.2025.130349_bb0090","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.ejphar.2013.11.021","article-title":"Clofarabine, a novel adenosine analogue, reactivates DNA methylation-silenced tumour suppressor genes and inhibits cell growth in breast cancer cells","volume":"723","author":"Lubecka-Pietruszewska","year":"2014","journal-title":"Eur J Pharmacol"},{"issue":"7","key":"10.1016\/j.bmcl.2025.130349_bb0095","doi-asserted-by":"crossref","first-page":"805","DOI":"10.2174\/138955709788452586","article-title":"Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity","volume":"9","author":"Ewa","year":"2009","journal-title":"Mini-Rev Med Chem"},{"issue":"1","key":"10.1016\/j.bmcl.2025.130349_bb0100","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/sj.bjp.0706446","article-title":"Antiviral prodrugs - the development of successful prodrug strategies for antiviral chemotherapy","volume":"147","author":"Clercq","year":"2006","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.bmcl.2025.130349_bb0105","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1016\/S0968-0896(00)00087-0","article-title":"The design and synthesis of a new tumor-selective fluoropyrimidine carbamate, capecitabine","volume":"8","author":"Shimma","year":"2000","journal-title":"Bioorg Med Chem"},{"key":"10.1016\/j.bmcl.2025.130349_bb0110","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2023.1173432","article-title":"Advanced prodrug strategies in nucleoside analogues targeting the treatment of gastrointestinal malignancies","volume":"11","author":"Xu","year":"2023","journal-title":"Front Cell Dev Biol"},{"issue":"11","key":"10.1016\/j.bmcl.2025.130349_bb0115","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1023\/A:1015968113838","article-title":"Synthesis, physicochemical properties, and cytotoxicity of a series of 5\u2032-ester prodrugs of 5\u2032-iodo-2\u2032-deoxyuridine","volume":"5","author":"Narurkar","year":"1988","journal-title":"Pharm Res"},{"issue":"15","key":"10.1016\/j.bmcl.2025.130349_bb0120","doi-asserted-by":"crossref","first-page":"4250","DOI":"10.1016\/j.bmcl.2009.05.099","article-title":"The application of phosphoramidate protide technology to the potent anti-HCV compound 4\u2032-azidocytidne (R1479)","volume":"19","year":"2009","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmcl.2025.130349_bb0125","doi-asserted-by":"crossref","first-page":"7524","DOI":"10.1038\/sj.onc.1206952","article-title":"Nucleoside anticancer drugs: the role of nucleoside transporters in resistance to cancer chemotherapy","volume":"22","author":"Damaraju","year":"2003","journal-title":"Oncogene"},{"issue":"6","key":"10.1016\/j.bmcl.2025.130349_bb0130","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1021\/acs.jmedchem.7b00734","article-title":"The protide prodrug technology: from concept to the clinic","volume":"61","author":"Mehellou","year":"2018","journal-title":"J Med Chem"},{"issue":"11","key":"10.1016\/j.bmcl.2025.130349_bb0135","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.3390\/v15112234","article-title":"The application of produgs as a tool to enhance the properties of nucleoside reverse transkiptase inhibitors","volume":"15","author":"Fernandes","year":"2023","journal-title":"Iviruses"},{"key":"10.1016\/j.bmcl.2025.130349_bb0140","doi-asserted-by":"crossref","first-page":"269","DOI":"10.4236\/pp.2024.158016","article-title":"Exploring ester prodrugs: a comprehensive review of approaches, applications and methods","volume":"15","author":"Zhou","year":"2024","journal-title":"Pharm Pharam"},{"issue":"23","key":"10.1016\/j.bmcl.2025.130349_bb0145","doi-asserted-by":"crossref","first-page":"6500","DOI":"10.1158\/1078-0432.CCR-21-1652","article-title":"The novel nucleoside analogue ProTide NUC-7738 overcomes cancer resistance mechanisms in vitro and in a first-in-human phase I clinical trial","volume":"27","author":"Schwenzer","year":"2021","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.bmcl.2025.130349_bb0150","series-title":"Development of novel clofarabine analogs for cancer therapy","author":"Moukha-Chafiq","year":"2024"},{"issue":"6\u20137","key":"10.1016\/j.bmcl.2025.130349_bb0155","first-page":"13","article-title":"Synthesis of some 2\u2032-deoxy-3\u2032-C-ethynyl beta-D-lyxofuranosyl nucleosides","volume":"24","author":"Moukha-Chafiq","year":"2005","journal-title":"Nucleosides, Nucleotides Nucleic Acids"}],"container-title":["Bioorganic &amp; Medicinal Chemistry Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X25002586?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X25002586?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:20:13Z","timestamp":1776918013000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0960894X25002586"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":31,"alternative-id":["S0960894X25002586"],"URL":"https:\/\/doi.org\/10.1016\/j.bmcl.2025.130349","relation":{},"ISSN":["0960-894X"],"issn-type":[{"value":"0960-894X","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery of a novel non-toxic analog of clofarabine for the treatment of triple\u2013negative breast cancer","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmcl.2025.130349","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"130349"}}