{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:46:43Z","timestamp":1788292003144,"version":"build-2803163510"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018694","name":"European Commission Marie Sklodowska-Curie Actions","doi-asserted-by":"publisher","award":["671881"],"award-info":[{"award-number":["671881"]}],"id":[{"id":"10.13039\/100018694","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["PE-2016-02363073"],"award-info":[{"award-number":["PE-2016-02363073"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["PE-2016-02362694"],"award-info":[{"award-number":["PE-2016-02362694"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["MCIN\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["MCIN\/AEI\/10.13039\/501100011033"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2020-116460RB-100"],"award-info":[{"award-number":["PID2020-116460RB-100"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["22098"],"award-info":[{"award-number":["22098"]}],"id":[{"id":"10.13039\/501100005010","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":[[2023,3]]},"DOI":"10.1016\/j.ejmech.2023.115170","type":"journal-article","created":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T02:45:23Z","timestamp":1675133123000},"page":"115170","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":9,"special_numbering":"C","title":["Synthesis and structure-activity relationship of new nicotinamide phosphoribosyltransferase inhibitors with antitumor activity on solid and haematological cancer"],"prefix":"10.1016","volume":"250","author":[{"given":"Simone","family":"Fratta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Biniecka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio J.","family":"Moreno-Vargas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana T.","family":"Carmona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimable","family":"Nahimana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel A.","family":"Duchosal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Piacente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santina","family":"Bruzzone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Caffa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Nencioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inmaculada","family":"Robina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2023.115170_bib1","first-page":"1","article-title":"NAD+ metabolism, stemness, the immune response, and cancer","volume":"6","author":"Navas","year":"2021","journal-title":"Signal Transduct. Targeted Ther."},{"key":"10.1016\/j.ejmech.2023.115170_bib2a","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/nrc3340","article-title":"The NAD metabolome\u2014a key determinant of cancer cell biology","volume":"12","author":"Chiarugi","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.ejmech.2023.115170_bib2b","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/s41586-019-1150-2","article-title":"NAD metabolic dependency in cancer is shaped by gene amplification and enhancer remodelling","author":"Chowdhry","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2023.115170_bib3","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.3390\/nu13051665","article-title":"Advances in NAD-lowering agents for cancer treatment","volume":"13","author":"Ghanem","year":"2021","journal-title":"Nutrients"},{"key":"10.1016\/j.ejmech.2023.115170_bib4","doi-asserted-by":"crossref","unstructured":"Wei, Y.; Xiang, H.; Zhang, W. Review of various NAMPT inhibitors for the treatment of cancer. Front. Pharmacol. 13:970553.","DOI":"10.3389\/fphar.2022.970553"},{"key":"10.1016\/j.ejmech.2023.115170_bib5","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/nsmb1105","article-title":"Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents","volume":"13","author":"Khan","year":"2006","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.ejmech.2023.115170_bib6","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s10637-007-9083-2","article-title":"The pharmacokinetics, toxicities, and biologic effects of FK866, a nicotinamide adenine dinucleotide biosynthesis inhibitor","volume":"16","author":"Holen","year":"2008","journal-title":"Invest. N. Drugs"},{"key":"10.1016\/j.ejmech.2023.115170_bib7","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1007\/s00280-009-1125-3","article-title":"Safety and efficacy of NAD depleting cancer drugs: results of a phase I clinical trial of CHS 828 and overview of published data","volume":"65","author":"von Heideman","year":"2010","journal-title":"Cancer Chemother. Pharmacol."},{"key":"10.1016\/j.ejmech.2023.115170_bib8","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/toxsci\/kfu268","article-title":"Retinal toxicity, in vivo and in vitro, associated with inhibition of nicotinamide phosphoribosyltransferase","volume":"144","author":"Zabka","year":"2015","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.ejmech.2023.115170_bib9a","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1158\/1535-7163.MCT-16-0197","article-title":"Dual and specific inhibition of NAMPT and PAK4 by KPT- 9274 decreases kidney cancer growth","volume":"15","author":"Aboud","year":"2016","journal-title":"Mol. Cancer Therapeut."},{"key":"10.1016\/j.ejmech.2023.115170_bib9b","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1158\/1078-0432.CCR-18-1776","article-title":"Dual PAK4-NAMPT inhibition impacts growth and survival, and increases sensitivity to DNA-damaging agents in waldenstrom macroglobulinemia","volume":"25","author":"Li","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ejmech.2023.115170_bib9c","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1182\/bloodadvances.2018024182","article-title":"Selective targeting of NAMPT by KPT-9274 in acute myeloid leukemia","volume":"3","author":"Mitchell","year":"2019","journal-title":"Blood Adv"},{"key":"10.1016\/j.ejmech.2023.115170_bib10","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1158\/1535-7163.MCT-20-1105","article-title":"Neuroendocrine tumors to everolimus","volume":"20","author":"Mpilla","year":"2021","journal-title":"Mol. Cancer Therapeut."},{"key":"10.1016\/j.ejmech.2023.115170_bib11","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1038\/s41375-019-0692-5","article-title":"OT-82, a novel anticancer drug candidate that targets the strong dependence of hematological malignancies on NAD biosynthesis","volume":"34","author":"Korotchkina","year":"2020","journal-title":"Leukemia"},{"key":"10.1016\/j.ejmech.2023.115170_bib12","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1021\/acs.jmedchem.6b01392","article-title":"Identification of novel triazole-based nicotinamide phosphoribosyltransferase (NAMPT) inhibitors endowed with antiproliferative and antiinflammatory activity","volume":"60","author":"Travelli","year":"2017","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115170_bib13","doi-asserted-by":"crossref","first-page":"9071","DOI":"10.1021\/jm4009949","article-title":"Nicotinamide phosphoribosyltransferase inhibitors, design, preparation, and structure\u2212activity relationship","volume":"56","author":"Christensen","year":"2013","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115170_bib14","doi-asserted-by":"crossref","first-page":"4921","DOI":"10.1021\/jm400186h","article-title":"Structure-based identification of ureas as novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitors","volume":"56","author":"Zheng","year":"2013","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115170_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2022.114504","article-title":"Identification of new FK866 analogues with potent anticancer activity against pancreatic cancer","volume":"239","author":"Bai","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115170_bib16","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1158\/1535-7163.MCT-16-0674","article-title":"Discovery of a highly selective NAMPT inhibitor that demonstrates robust efficacy and improved retinal toxicity with nicotinic acid coadministration","volume":"16","author":"Zhao","year":"2017","journal-title":"Mol. Cancer Therapeut."},{"key":"10.1016\/j.ejmech.2023.115170_bib17","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1021\/acschembio.6b00444","article-title":"Albumin-oxanorbornadiene conjugates formed ex vivo for the extended circulation of hydrophilic cargo","volume":"11","author":"Higginson","year":"2016","journal-title":"ACS Chem. Biol."},{"key":"10.1016\/j.ejmech.2023.115170_bib18","doi-asserted-by":"crossref","first-page":"3528","DOI":"10.1021\/jacs.6b12964","article-title":"Efficient liver targeting by polyvalent display of a compact ligand for the asialoglycoprotein receptor","volume":"139","author":"Sanhueza","year":"2017","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2023.115170_bib19","series-title":"A.\u201cPiperidine Derivatives for Use in the Treatment of Pancreatic Cancer\u201d","author":"Duchosal","year":"2018"},{"key":"10.1016\/j.ejmech.2023.115170_bib20","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1039\/D1MD00058F","article-title":"Recent advances in urea- and thiourea-containing compounds: focus on innovative approaches in medicinal chemistry and organic synthesis","volume":"12","author":"Ronchetti","year":"2021","journal-title":"RSC Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115170_bib21","doi-asserted-by":"crossref","first-page":"4921","DOI":"10.1021\/jm400186h","article-title":"Structure-based identification of ureas as novel Nicotinamidephosphoribosyltransferase (Nampt) inhibitors","volume":"56","author":"Zheng","year":"2013","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115170_bib22","unstructured":"Compound 31 Was Prepared Following an Alternative Procedure by N-Chlorosuccinimide-Mediated Oxidation (See Supplementary Material) that Showed to Be More Efficient than the One Previously Described in Reference 13."},{"key":"10.1016\/j.ejmech.2023.115170_bib23","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.ejmech.2017.02.060","article-title":"Discovery and pharmacological evaluation of a novel series of adamantyl cyanoguanidines as P2X7 receptor antagonists","volume":"130","author":"O'Brien-Brown","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115170_bib24","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/nsmb1105","article-title":"Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents","volume":"13","author":"Khan","year":"2006","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.ejmech.2023.115170_bib25","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1158\/1535-7163.MCT-16-0819","article-title":"Discovery and characterization of novel nonsubstrate and substrate NAMPT inhibitors","volume":"16","author":"Wilsbacher","year":"2017","journal-title":"Mol. Cancer Therapeut."},{"key":"10.1016\/j.ejmech.2023.115170_bib26","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1002\/cbic.201402023","article-title":"Structural and biochemical analyses of the catalysis and potency impact of inhibitor phosphoribosylation by human nicotinamide phosphoribosyltransferase","volume":"15","author":"Oh","year":"2014","journal-title":"Chembiochem"},{"key":"10.1016\/j.ejmech.2023.115170_bib27","doi-asserted-by":"crossref","first-page":"656","DOI":"10.3389\/fphar.2020.00656","article-title":"Recent advances in NAMPT inhibitors: a novel immunotherapic strategy","volume":"11","author":"Galli","year":"2020","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.ejmech.2023.115170_bib28","doi-asserted-by":"crossref","first-page":"e1599","DOI":"10.1038\/cddis.2014.564","article-title":"NAMPT inhibition sensitizes pancreatic adenocarcinoma cells to tumor-selective, PAR-independent metabolic catastrophe and cell death induced by \u03b2-lapachone","volume":"6","author":"Moore","year":"2015","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.ejmech.2023.115170_bib29","doi-asserted-by":"crossref","first-page":"3276","DOI":"10.1182\/blood-2008-08-173369","article-title":"The NAD biosynthesis inhibitor APO866 has potent antitumor activity against hematologic malignancies","volume":"113","author":"Nahimana","year":"2009","journal-title":"Blood"},{"key":"10.1016\/j.ejmech.2023.115170_bib30","first-page":"7436","article-title":"FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis","volume":"63","author":"Hasmann","year":"2003","journal-title":"Cancer Res."},{"key":"10.1016\/j.ejmech.2023.115170_bib31","doi-asserted-by":"crossref","first-page":"603","DOI":"10.4161\/auto.27722","article-title":"A critical role of autophagy in antileukemia\/lymphoma effects of APO866, an inhibitor of NAD biosynthesis","volume":"10","author":"Ginet","year":"2014","journal-title":"Autophagy"},{"key":"10.1016\/j.ejmech.2023.115170_bib32","doi-asserted-by":"crossref","first-page":"6723","DOI":"10.18632\/oncotarget.27336","article-title":"Reactive oxygen\/nitrogen species contribute substantially to the antileukemia effect of APO866, a NAD lowering agent","volume":"10","author":"Cloux","year":"2019","journal-title":"Oncotarget"},{"key":"10.1016\/j.ejmech.2023.115170_bib33","doi-asserted-by":"crossref","first-page":"4373","DOI":"10.1002\/anie.200351930","article-title":"Intramolecular staudinger ligation: a powerful ring-closure method to form medium-sized lactams","volume":"42","author":"David","year":"2003","journal-title":"Angew. Chem. Int. Ed."},{"key":"10.1016\/j.ejmech.2023.115170_bib34","doi-asserted-by":"crossref","first-page":"8161","DOI":"10.1021\/acs.jmedchem.0c02169","article-title":"Development of covalent, clickable probes for adenosine A1 and A3 receptors","volume":"64","author":"Trinh","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115170_bib35","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/cmdc.201600563","article-title":"Inhibition of the cysteine protease human cathepsin L by triazine nitriles : amide \u00b7\u00b7\u00b7 heteroarene p -stacking interactions and chalcogen bonding in the S3 pocket","volume":"12","author":"Giroud","year":"2017","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2023.115170_bib36","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1021\/jm010985a","article-title":"Design, synthesis, and pharmacological evaluation of thapsigargin analogues for targeting apoptosis to prostatic cancer cells","volume":"44","author":"Jakobsen","year":"2001","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115170_bib37","doi-asserted-by":"crossref","first-page":"9071","DOI":"10.1021\/jm4009949","article-title":"Nicotinamide phosphoribosyltransferase inhibitors, design, preparation, and structure \u2212 activity relationship","volume":"56","author":"Christensen","year":"2013","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115170_bib38","doi-asserted-by":"crossref","first-page":"6516","DOI":"10.1021\/jo101234u","article-title":"Very contracted to extended Co -conformations with or without oscillations in two- and three-station [\u20192]Daisy chains","volume":"75","author":"Romuald","year":"2010","journal-title":"J. Org. Chem."},{"key":"10.1016\/j.ejmech.2023.115170_bib39","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.1016\/j.bmcl.2017.06.018","article-title":"SAR and characterization of non-substrate isoindoline urea inhibitors of nicotinamide phosphoribosyltransferase (NAMPT)","volume":"27","author":"Curtin","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2023.115170_bib40","doi-asserted-by":"crossref","first-page":"3704","DOI":"10.1096\/fj.201800321R","article-title":"SIRT6 deacetylase activity regulates NAMPT activity and NAD(P)(H) pools in cancer cells","volume":"33","author":"Sociali","year":"2019","journal-title":"Faseb. J."},{"key":"10.1016\/j.ejmech.2023.115170_bib41","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ab.2010.12.035","article-title":"A fluorometric assay for high-throughput screening targeting nicotinamide phosphoribosyltransferase","volume":"412","author":"Zhang","year":"2011","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.ejmech.2023.115170_bib42","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1002\/bies.10297","article-title":"Reconstructing eukaryotic NAD metabolism","volume":"25","author":"Rongvaux","year":"2003","journal-title":"Bioessays"}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523423000855?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523423000855?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T06:03:32Z","timestamp":1777529012000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523423000855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3]]},"references-count":45,"alternative-id":["S0223523423000855"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2023.115170","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2023,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Synthesis and structure-activity relationship of new nicotinamide phosphoribosyltransferase inhibitors with antitumor activity on solid and haematological cancer","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2023.115170","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Published by Elsevier Masson SAS.","name":"copyright","label":"Copyright"}],"article-number":"115170"}}