{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T11:39:51Z","timestamp":1770464391398,"version":"3.49.0"},"reference-count":54,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Seventh Framework Program PANACREAS","award":["GA #256986"],"award-info":[{"award-number":["GA #256986"]}]},{"name":"Seventh Framework Program PANACREAS","award":["#813284-1"],"award-info":[{"award-number":["#813284-1"]}]},{"name":"European FP7 project INTEGRATA","award":["GA #256986"],"award-info":[{"award-number":["GA #256986"]}]},{"name":"European FP7 project INTEGRATA","award":["#813284-1"],"award-info":[{"award-number":["#813284-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Targeting cancer cells that are highly dependent on the nicotinamide adenine dinucleotide (NAD+) metabolite is a promising therapeutic strategy. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme catalyzing NAD+ production. Despite the high efficacy of several developed NAMPT inhibitors (i.e., FK866 (APO866)) in preclinical studies, their clinical activity was proven to be limited. Here, we report the synthesis of new NAMPT Inhibitors, JJ08, FEI191 and FEI199, which exhibit a broad anticancer activity in vitro. Results show that these compounds are potent NAMPT inhibitors that deplete NAD+ and NADP(H) after 24 h of drug treatment, followed by an increase in reactive oxygen species (ROS) accumulation. The latter event leads to ATP loss and mitochondrial depolarization with induction of apoptosis and necrosis. Supplementation with exogenous NAD+ precursors or catalase (ROS scavenger) abrogates the cell death induced by the new compounds. Finally, in vivo administration of the new NAMPT inhibitors in a mouse xenograft model of human Burkitt lymphoma delays tumor growth and significantly prolongs mouse survival. The most promising results are collected with JJ08, which completely eradicates tumor growth. Collectively, our findings demonstrate the efficient anticancer activity of the new NAMPT inhibitor JJ08 and highlight a strong interest for further evaluation of this compound in hematological malignancies.<\/jats:p>","DOI":"10.3390\/molecules28041897","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T01:32:56Z","timestamp":1676597576000},"page":"1897","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Anticancer Activities of Novel Nicotinamide Phosphoribosyltransferase Inhibitors in Hematological Malignancies"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0293-5793","authenticated-orcid":false,"given":"Paulina","family":"Biniecka","sequence":"first","affiliation":[{"name":"Central Laboratory of Hematology, Department of Medical Laboratory and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3742-2384","authenticated-orcid":false,"given":"Saki","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Central Laboratory of Hematology, Department of Medical Laboratory and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Belotti","sequence":"additional","affiliation":[{"name":"Central Laboratory of Hematology, Department of Medical Laboratory and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessie","family":"Joussot","sequence":"additional","affiliation":[{"name":"Laboratory of Glycochemistry and Asymmetric Synthesis, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, 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Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5470-5987","authenticated-orcid":false,"given":"Francesco","family":"Piacente","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Biochemistry, University of Genoa, 16132 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2034-3716","authenticated-orcid":false,"given":"Santina","family":"Bruzzone","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Biochemistry, University of Genoa, 16132 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1530-6729","authenticated-orcid":false,"given":"Michele","family":"Cea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties, University of Genoa, 16132 Genoa, Italy"},{"name":"Ospedale Policlinico San Martino IRCCS, Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent A.","family":"Decosterd","sequence":"additional","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7399-2341","authenticated-orcid":false,"given":"Pierre","family":"Vogel","sequence":"additional","affiliation":[{"name":"Laboratory of Glycochemistry and Asymmetric Synthesis, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessio","family":"Nencioni","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties, University of Genoa, 16132 Genoa, Italy"},{"name":"Ospedale Policlinico San Martino IRCCS, Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel A.","family":"Duchosal","sequence":"additional","affiliation":[{"name":"Central Laboratory of Hematology, Department of Medical Laboratory and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"},{"name":"Service of Hematology, Department of Oncology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4968-3167","authenticated-orcid":false,"given":"Aimable","family":"Nahimana","sequence":"additional","affiliation":[{"name":"Central Laboratory of Hematology, Department of Medical Laboratory and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, 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