{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:17:51Z","timestamp":1760059071400,"version":"build-2065373602"},"reference-count":46,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Practice Plan (Faculty of Medicine, AUB to H.E.H.)"},{"name":"Universit\u00e9 de Montpellier\/Centre National de Recherche Scientifique-Liban"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Although 60% of AML patients respond well to standard chemotherapy, most patients eventually relapse, develop chemoresistance, and do not survive more than five years. Targeted therapies, including analogs of imiquimod belonging to the family of imiqualines, emerged as promising agents against AML. Notably, the first-generation imiqualine EAPB0503 proved selective potency against nucleophosmin-1-mutant (NPM1c) AML. Recently, chemical modifications of EAPB0503 led to the development of the lead compound from the second generation, EAPB02303. Here, we demonstrate that EAPB02303 displays 200-fold greater potency, broader activity across AML subtypes, and, importantly, a distinct mechanistic profile when compared to EAPB0503. Unlike EAPB0503, which primarily targeted NPM1c AML cells, EAPB02303 exhibits broad-spectrum activity across various AML subtypes. Remarkably, EAPB02303 anti-leukemic activity was attributed to the inhibition of PI3K\/AKT\/mTOR signaling activity. Nevertheless, NPM1c AML cells were more sensitive to EAPB02303, likely due to its ability to promote NPM1c protein degradation. In vivo, EAPB02303 potently reduced the leukemic burden and improved organ tumor infiltration in both wt-NPM1 and NPM1c AML xenograft mice. Yet, the significant prolonged survival was exclusive to NPM1c AML xenografts, likely due to superior response conferred by NPM1c degradation. Overall, these findings highlight the potential of EAPB02303 as a powerful therapeutic agent for a range of AML subtypes, supporting its further development for broader clinical use.<\/jats:p>","DOI":"10.3390\/biom15050741","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T04:05:17Z","timestamp":1747800317000},"page":"741","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Novel Imiqualine EAPB02303 Is a Potent Drug for Treating Acute Myeloid Leukemia"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3114-7888","authenticated-orcid":false,"given":"Perla","family":"Makhoul","sequence":"first","affiliation":[{"name":"Institut des Biomol\u00e9cules Max Mousseron (IBMM), UMR 5247, CNRS, ENSCM, Universit\u00e9 de Montpellier, 34090 Montpellier, France"},{"name":"Department of Biology, Faculty of Sciences, GSBT Laboratory, Lebanese University, R. Hariri Campus, Hadath 1533, Lebanon"},{"name":"Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut P.O. Box 113-6044, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Hleihel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut P.O. Box 113-6044, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaymaa","family":"Itani","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut P.O. Box 113-6044, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maguy","family":"Hamie","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut P.O. Box 113-6044, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Pagniagua-Gayraud","sequence":"additional","affiliation":[{"name":"Institut des Biomol\u00e9cules Max Mousseron (IBMM), UMR 5247, CNRS, ENSCM, Universit\u00e9 de Montpellier, 34090 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5854-310X","authenticated-orcid":false,"given":"Cindy","family":"Patinote","sequence":"additional","affiliation":[{"name":"Institut des Biomol\u00e9cules Max Mousseron (IBMM), UMR 5247, CNRS, ENSCM, Universit\u00e9 de Montpellier, 34090 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7720-8569","authenticated-orcid":false,"given":"Myriam","family":"Richaud","sequence":"additional","affiliation":[{"name":"Institut des Biomol\u00e9cules Max Mousseron (IBMM), UMR 5247, CNRS, ENSCM, Universit\u00e9 de Montpellier, 34090 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3299-8595","authenticated-orcid":false,"given":"Raghida Abou","family":"Merhi","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Sciences, GSBT Laboratory, Lebanese University, R. Hariri Campus, Hadath 1533, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwan","family":"El-Sabban","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut P.O. Box 113-6044, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1717-1266","authenticated-orcid":false,"given":"Simon","family":"Galas","sequence":"additional","affiliation":[{"name":"Institut des Biomol\u00e9cules Max Mousseron (IBMM), UMR 5247, CNRS, ENSCM, Universit\u00e9 de Montpellier, 34090 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4086-5178","authenticated-orcid":false,"given":"Carine","family":"Deleuze-Masquefa","sequence":"additional","affiliation":[{"name":"Institut des Biomol\u00e9cules Max Mousseron (IBMM), UMR 5247, CNRS, ENSCM, Universit\u00e9 de Montpellier, 34090 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8579-4150","authenticated-orcid":false,"given":"Pierre-Antoine","family":"Bonnet","sequence":"additional","affiliation":[{"name":"Institut des Biomol\u00e9cules Max Mousseron (IBMM), UMR 5247, CNRS, ENSCM, Universit\u00e9 de Montpellier, 34090 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1069-0477","authenticated-orcid":false,"given":"Hiba","family":"El Hajj","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut P.O. Box 113-6044, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1056\/NEJMra1406184","article-title":"Acute Myeloid Leukemia","volume":"373","author":"Weisdorf","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_2","unstructured":"Vakiti, A., Reynolds, S.B., and Mewawalla, P. (2024). Acute Myeloid Leukemia. StatPearls, StatPearls Publishing LLC.. StatPearls Publishing Copyright \u00a9 2024."},{"key":"ref_3","unstructured":"(2024, July 11). 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