{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T01:52:35Z","timestamp":1773971555667,"version":"3.50.1"},"reference-count":67,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100015796","name":"Shanghai Lingjun Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015796","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81702600"],"award-info":[{"award-number":["81702600"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012600","name":"ShanghaiTech University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012600","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":[[2026,3]]},"DOI":"10.1016\/j.ejmech.2025.118546","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T23:31:03Z","timestamp":1767223863000},"page":"118546","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Discovery of novel and potent harringtonine derivative P2 via systematic structure-activity Optimization: Semi-Synthesis, anti-leukemia activity, and mechanism study"],"prefix":"10.1016","volume":"305","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1178-6331","authenticated-orcid":false,"given":"Zhongli","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuting","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyu","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dejin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanchao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Xing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongli","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianqian","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biao","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2025.118546_bib1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/s41408-023-00853-3","article-title":"Global burden of hematologic malignancies and evolution patterns over the past 30 years","volume":"13","author":"Zhang","year":"2023","journal-title":"Blood Cancer J."},{"key":"10.1016\/j.ejmech.2025.118546_bib2","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/s41375-024-02452-y","article-title":"Global patterns of leukemia by subtype, age, and sex in 185 countries in 2022","volume":"39","author":"Daltveit","year":"2025","journal-title":"Leukemia"},{"key":"10.1016\/j.ejmech.2025.118546_bib3","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/S1470-2045(25)00017-8","article-title":"Cancer incidence and mortality estimates in 2022 in southeast Asia: a comparative analysis","volume":"26","author":"Dee","year":"2025","journal-title":"Lancet Oncol."},{"key":"10.1016\/j.ejmech.2025.118546_bib4","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s40364-024-00649-y","article-title":"Global, regional, and national burden of acute myeloid leukemia, 1990-2021: a systematic analysis for the global burden of disease study 2021","volume":"12","author":"Zhou","year":"2024","journal-title":"Biomark. Res."},{"key":"10.1016\/j.ejmech.2025.118546_bib5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3324\/haematol.2021.280161","article-title":"The \"7+3\" regimen in acute myeloid leukemia","volume":"107","author":"Rowe","year":"2022","journal-title":"Haematologica"},{"key":"10.1016\/j.ejmech.2025.118546_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.blre.2025.101288","article-title":"Navigating acute myeloid leukemia towards better outcomes: treatment pathways and challenges for patients ineligible for intensive chemotherapy","volume":"73","author":"Palmieri","year":"2025","journal-title":"Blood Rev."},{"key":"10.1016\/j.ejmech.2025.118546_bib7","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.clml.2024.12.009","article-title":"Clinical outcomes of patients with newly diagnosed acute myeloid leukemia receiving treatment in a safety-net hospital System","volume":"25","author":"Lu","year":"2025","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"10.1016\/j.ejmech.2025.118546_bib8","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1002\/cncr.31347","article-title":"How I treat older patients with acute myeloid leukemia","volume":"124","author":"Arellano","year":"2018","journal-title":"Cancer"},{"key":"10.1016\/j.ejmech.2025.118546_bib9","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","article-title":"Natural products in drug discovery: advances and opportunities","volume":"20","author":"Atanasov","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2025.118546_bib10","doi-asserted-by":"crossref","DOI":"10.3390\/molecules27238367","article-title":"Natural products as anticancer agents: current status and future perspectives","volume":"27","author":"Naeem","year":"2022","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2025.118546_bib11","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1021\/jo01044a010","article-title":"The alkaloids of Cephalotaxus drupacea and Cephalotaxus fortunei","volume":"28","author":"Paudler","year":"1963","journal-title":"J. Org. Chem."},{"key":"10.1016\/j.ejmech.2025.118546_bib12","doi-asserted-by":"crossref","first-page":"4081","DOI":"10.1016\/S0040-4039(01)88620-2","article-title":"Structure of cephalotaxine and related alkaloids","volume":"10","author":"Powell","year":"1969","journal-title":"Tetra. Lett."},{"key":"10.1016\/j.ejmech.2025.118546_bib13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1756-8722-2-32","article-title":"A homoharringtonine-based induction regimen for the treatment of elderly patients with acute myeloid leukemia: a single center experience from China","volume":"2","author":"Wang","year":"2009","journal-title":"J. Hematol. Oncol."},{"key":"10.1016\/j.ejmech.2025.118546_bib14","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/S1470-2045(13)70152-9","article-title":"Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial","volume":"14","author":"Jin","year":"2013","journal-title":"Lancet Oncol."},{"key":"10.1016\/j.ejmech.2025.118546_bib15","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1158\/1078-0432.CCR-13-1283","article-title":"Omacetaxine: a protein translation inhibitor for treatment of chronic myelogenous leukemia","volume":"20","author":"Gandhi","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ejmech.2025.118546_bib16","first-page":"605","article-title":"A phase II open\u2010label study of the intravenous administration of homoharringtonine in the treatment of myelodysplastic syndrome","volume":"22","author":"Daver","year":"2013","journal-title":"Eur. J. Cancer Care"},{"key":"10.1016\/j.ejmech.2025.118546_bib17","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1182\/blood-2012-03-415307","article-title":"Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation","volume":"120","author":"Cortes","year":"2012","journal-title":"Blood"},{"key":"10.1016\/j.ejmech.2025.118546_bib18","first-page":"19891","article-title":"Sorafenib in combination with low-dose-homoharringtonine as a salvage therapy in primary refractory FLT3-ITD-positive AML: a case report and review of literature","volume":"8","author":"Xu","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"10.1016\/j.ejmech.2025.118546_bib19","first-page":"25","article-title":"Homoharringtonine, a clinically approved anti-leukemia drug, sensitizes tumor cells for TRAIL-induced necroptosis, Cell Commun","volume":"13","author":"Philipp","year":"2015","journal-title":"Signal"},{"key":"10.1016\/j.ejmech.2025.118546_bib20","article-title":"Synergistic effect and molecular mechanism of homoharringtonine and Bortezomib on SKM-1 cell apoptosis","volume":"10","author":"Zhang","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.ejmech.2025.118546_bib21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0164238","article-title":"HAG (Homoharringtonine, cytarabine, G-CSF) regimen for the treatment of Acute Myeloid leukemia and myelodysplastic syndrome: a meta-analysis with 2,314 participants","volume":"11","author":"Xie","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.ejmech.2025.118546_bib22","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1080\/10428194.2017.1283030","article-title":"Phase II trial of homoharringtonine with imatinib in chronic, accelerated, and blast phase chronic myeloid leukemia","volume":"58","author":"Maiti","year":"2017","journal-title":"Leuk. Lymph."},{"key":"10.1016\/j.ejmech.2025.118546_bib23","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1186\/s12885-018-5018-x","article-title":"Homoharringtonine interacts synergistically with bortezomib in NHL cells through MCL-1 and NOXA-dependent mechanisms","volume":"18","author":"Nguyen","year":"2018","journal-title":"BMC Cancer"},{"key":"10.1016\/j.ejmech.2025.118546_bib24","article-title":"Acute myeloid leukemia in an 86-year-old man with AML1\/ETO treated with Homoharringtonine and Arsenic trioxide: a case report","volume":"98","author":"He","year":"2019","journal-title":"Medicine (Baltim.)"},{"key":"10.1016\/j.ejmech.2025.118546_bib25","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1186\/s13046-019-1295-8","article-title":"Synergistic killing effects of homoharringtonine and arsenic trioxide on acute myeloid leukemia stem cells and the underlying mechanisms","volume":"38","author":"Tan","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"10.1016\/j.ejmech.2025.118546_bib26","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.tranon.2019.02.016","article-title":"Homoharringtonine combined with the heat shock protein 90 inhibitor IPI504 in the treatment of FLT3-ITD acute myeloid leukemia","volume":"12","author":"Wu","year":"2019","journal-title":"Transl. Oncol."},{"key":"10.1016\/j.ejmech.2025.118546_bib27","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aaf3735","article-title":"Homoharringtonine (omacetaxine mepesuccinate) as an adjunct for FLT3-ITD acute myeloid leukemia","volume":"8","author":"Lam","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ejmech.2025.118546_bib28","doi-asserted-by":"crossref","first-page":"3205","DOI":"10.1002\/cam4.913","article-title":"Homoharringtonine combined with aclarubicin and cytarabine synergistically induces apoptosis in t(8;21) leukemia cells and triggers caspase-3-mediated cleavage of the AML1-ETO oncoprotein","volume":"5","author":"Cao","year":"2016","journal-title":"Cancer Med."},{"key":"10.1016\/j.ejmech.2025.118546_bib29","doi-asserted-by":"crossref","first-page":"355","DOI":"10.3892\/ol.2015.3876","article-title":"Efficacy and safety of homoharringtonine plus cytarabine and aclarubicin for patients with myelodysplastic syndrome-RAEB","volume":"11","author":"Xiao","year":"2016","journal-title":"Oncol. Lett."},{"key":"10.1016\/j.ejmech.2025.118546_bib30","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.leukres.2016.02.012","article-title":"Homoharringtonine, aclarubicin and cytarabine (HAA) regimen as the first course of induction therapy is highly effective for acute myeloid leukemia with t (8;21)","volume":"44","author":"Zhu","year":"2016","journal-title":"Leuk. Res."},{"key":"10.1016\/j.ejmech.2025.118546_bib31","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1038\/sj.leu.2404287","article-title":"Homoharringtonine in combination with cytarabine and aclarubicin resulted in high complete remission rate after the first induction therapy in patients with de novo acute myeloid leukemia","volume":"20","author":"Jin","year":"2006","journal-title":"Leukemia"},{"key":"10.1016\/j.ejmech.2025.118546_bib32","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1007\/s00277-013-1758-5","article-title":"Homoharringtonine in combination with cytarabine and aclarubicin in the treatment of refractory\/relapsed acute myeloid leukemia: a single-center experience","volume":"92","author":"Yu","year":"2013","journal-title":"Ann. Hematol."},{"key":"10.1016\/j.ejmech.2025.118546_bib33","doi-asserted-by":"crossref","first-page":"4881","DOI":"10.1200\/JCO.22.02836","article-title":"Homoharringtonine-based induction regimen improved the remission rate and survival rate in Chinese childhood AML: a report from the CCLG-AML 2015 protocol study","volume":"41","author":"Li","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.ejmech.2025.118546_bib34","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2020.104445","article-title":"Cytotoxic secondary metabolites from the vulnerable conifer Cephalotaxus oliveri and its associated endophytic fungus alternaria alternate Y-4-2","volume":"105","author":"Ma","year":"2020","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2025.118546_bib35","doi-asserted-by":"crossref","first-page":"4162","DOI":"10.1021\/jo00445a045","article-title":"Synthetic studies on the side chains of cephalotaxus esters","volume":"42","author":"Bates","year":"1977","journal-title":"J. Org. Chem."},{"key":"10.1016\/j.ejmech.2025.118546_bib36","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.1039\/b605339d","article-title":"Synthesis of the ester side chains of some potently antileukemic harringtonia alkaloids from chiral citrates","author":"Ancliff","year":"2006","journal-title":"Chem. Commun. (Camb)"},{"key":"10.1016\/j.ejmech.2025.118546_bib37","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1046\/j.1359-4117.2003.01066.x","article-title":"Metabolism of homoharringtonine, a cytotoxic component of the evergreen plant Cephalotaxus harringtonia","volume":"3","author":"Ni","year":"2003","journal-title":"J. Exp. Ther. Oncol."},{"key":"10.1016\/j.ejmech.2025.118546_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2022.114731","article-title":"Enantioselective semisynthesis of novel cephalotaxine esters with potent antineoplastic activities against leukemia","volume":"244","author":"Yang","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118546_bib39","series-title":"Studies in Natural Products Chemistry","first-page":"339","article-title":"Chapter 10 - chemistry, bioactivity, and the structure-activity relationship of cephalotaxine-type alkaloids from cephalotaxus sp","author":"Chang","year":"2017"},{"key":"10.1016\/j.ejmech.2025.118546_bib40","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1021\/acs.jnatprod.1c00888","article-title":"Harringtonine ester derivatives with enhanced antiproliferative activities against HL-60 and HeLa cells","volume":"85","author":"Ochi","year":"2022","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.ejmech.2025.118546_bib41","series-title":"MSK","article-title":"Cephalotaxus esters, methods of synthesis, and uses thereof","author":"Gin","year":"2009"},{"key":"10.1016\/j.ejmech.2025.118546_bib42","series-title":"Cephalotaxanes, their Method of Preparation and their Use in Treatment of Cancers, Leukemias, Parasites Including those Resistant to Usual Chemotherapeutic Agents and as Reversal Agents","author":"Robin","year":"2004"},{"key":"10.1016\/j.ejmech.2025.118546_bib43","series-title":"New Cephalotaxanes, their Method of Preparation and their Use in Treatment of Cancers, Leukemias, Parasites Including those Resistant to Usual Chemotherapeutic Agents and as Reversal Agents, WO2002032904","author":"Robin","year":"2002"},{"key":"10.1016\/j.ejmech.2025.118546_bib44","article-title":"Method for synthesizing ester derivative of (-)-cephalotaxine for treating leukemia and malignant lymphoma, and intermediate thereof","volume":"A","author":"Jiang","year":"2019","journal-title":"CN110577506"},{"key":"10.1016\/j.ejmech.2025.118546_bib45","doi-asserted-by":"crossref","first-page":"5602","DOI":"10.1128\/AAC.00246-11","article-title":"Antitrypanosomal activity of fexinidazole, a new oral nitroimidazole drug candidate for treatment of sleeping sickness","volume":"55","author":"Kaiser","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2025.118546_bib46","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.jhep.2015.10.024","article-title":"Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis","volume":"64","author":"Baghdasaryan","year":"2016","journal-title":"J. Hepatol."},{"key":"10.1016\/j.ejmech.2025.118546_bib47","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1177\/1479164114548027","article-title":"The dual peroxisome proliferator-activated receptor alpha\/delta agonist GFT505 exerts anti-diabetic effects in db\/db mice without peroxisome proliferator-activated receptor gamma-associated adverse cardiac effects","volume":"11","author":"Hanf","year":"2014","journal-title":"Diab. Vasc. Dis. Res."},{"key":"10.1016\/j.ejmech.2025.118546_bib48","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1210\/jc.2011-1061","article-title":"MBX-8025, a novel peroxisome proliferator receptor-delta agonist: lipid and other metabolic effects in dyslipidemic overweight patients treated with and without atorvastatin","volume":"96","author":"Bays","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.ejmech.2025.118546_bib49","series-title":"Synthetic Method of Chiral (-)-cephalotaxine and Intermediate Thereof, In, China","author":"Jiang","year":"2017"},{"key":"10.1016\/j.ejmech.2025.118546_bib50","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.jmb.2009.04.005","article-title":"U2504 determines the species specificity of the A-Site cleft antibiotics:: the structures of Tiamulin, homoharringtonine, and bruceantin bound to the ribosome","volume":"389","author":"G\u00fcrel","year":"2009","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.ejmech.2025.118546_bib51","first-page":"205","article-title":"Cephalotaxus alkaloids, alkaloids","volume":"78","author":"P\u00e9rard-Viret","year":"2017","journal-title":"Chem. Biol."},{"key":"10.1016\/j.ejmech.2025.118546_bib52","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1021\/acs.orglett.7b00743","article-title":"Diastereoselective synthesis of cephalotaxus esters via asymmetric Mukaiyama Aldol reaction","volume":"19","author":"Ma","year":"2017","journal-title":"Org. Lett."},{"key":"10.1016\/j.ejmech.2025.118546_bib53","doi-asserted-by":"crossref","unstructured":"D. Ni, D.H. Ho, M. Vijjeswarapu, E. Felix, P.R. Rhea, R. A. Newman, Metabolism of homoharringtonine, a cytotoxic component of the evergreen plant Cephalotaxus harringtonia, J. Exp. Ther. Oncol. 3, 47-52.","DOI":"10.1046\/j.1359-4117.2003.01066.x"},{"key":"10.1016\/j.ejmech.2025.118546_bib54","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nature13737","article-title":"Structural basis for the inhibition of the eukaryotic ribosome","volume":"513","author":"Garreau de Loubresse","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2025.118546_bib55","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1080\/00397919508011401","article-title":"The mannich reaction of malonic acid. An efficient route to some \u03b1-Functionalized acrylates","volume":"25","author":"Krawczyk","year":"1995","journal-title":"Synth. Commun."},{"key":"10.1016\/j.ejmech.2025.118546_bib56","doi-asserted-by":"crossref","first-page":"6808","DOI":"10.1002\/anie.201701394","article-title":"Enzyme-Inspired chiral secondary-phosphine-oxide ligand with dual noncovalent interactions for asymmetric hydrogenation","volume":"56","author":"Chen","year":"2017","journal-title":"Angew. Chem. Int. Ed."},{"key":"10.1016\/j.ejmech.2025.118546_bib57","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1080\/10428194.2024.2400228","article-title":"Homoharringtonine sensitized resistant acute myeloid leukemia cells to venetoclax-induced apoptosis","volume":"65","author":"Yin","year":"2024","journal-title":"Leuk. Lymph."},{"key":"10.1016\/j.ejmech.2025.118546_bib58","article-title":"Cephalotaxine inhibits the survival of leukemia cells by activating mitochondrial apoptosis pathway and inhibiting autophagy flow","volume":"26","author":"Liu","year":"2021","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2025.118546_bib59","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1182\/blood-2010-01-262808","article-title":"Homoharringtonine reduced Mcl-1 expression and induced apoptosis in chronic lymphocytic leukemia","volume":"117","author":"Chen","year":"2011","journal-title":"Blood"},{"key":"10.1016\/j.ejmech.2025.118546_bib60","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2025.118025","article-title":"Homoharringtonine (omacetaxine mepesuccinate) limits the angiogenic capacity of endothelial cells and reorganises filamentous actin","volume":"186","author":"V\u00f6lkl","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.ejmech.2025.118546_bib61","doi-asserted-by":"crossref","first-page":"8275","DOI":"10.1038\/s41598-022-12000-2","article-title":"Targeting the translational machinery in gastrointestinal stromal tumors (GIST): a new therapeutic vulnerability","volume":"12","author":"Lee","year":"2022","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejmech.2025.118546_bib62","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41571-021-00549-2","article-title":"The MYC oncogene - the grand orchestrator of cancer growth and immune evasion","volume":"19","author":"Dhanasekaran","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.ejmech.2025.118546_bib63","doi-asserted-by":"crossref","DOI":"10.1016\/j.ctrv.2021.102154","article-title":"MYC as a target for cancer treatment","volume":"94","author":"Duffy","year":"2021","journal-title":"Cancer Treat Rev."},{"key":"10.1016\/j.ejmech.2025.118546_bib64","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1038\/s42003-021-02564-6","article-title":"The multiple mechanisms of MCL1 in the regulation of cell fate","volume":"4","author":"Widden","year":"2021","journal-title":"Commun. Biol."},{"key":"10.1016\/j.ejmech.2025.118546_bib65","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Sastry","year":"2013","journal-title":"J. Comput. Aided Mol. Des."},{"key":"10.1016\/j.ejmech.2025.118546_bib66","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/prot.10613","article-title":"A hierarchical approach to all-atom protein loop prediction","volume":"55","author":"Jacobson","year":"2004","journal-title":"Proteins"},{"key":"10.1016\/j.ejmech.2025.118546_bib67","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s10822-010-9349-1","article-title":"Towards the comprehensive, rapid, and accurate prediction of the favorable tautomeric states of drug-like molecules in aqueous solution","volume":"24","author":"Greenwood","year":"2010","journal-title":"J. Comput. Aided Mol. Des."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S022352342501311X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S022352342501311X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:40:14Z","timestamp":1773967214000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S022352342501311X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":67,"alternative-id":["S022352342501311X"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.118546","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery of novel and potent harringtonine derivative P2 via systematic structure-activity Optimization: Semi-Synthesis, anti-leukemia activity, and mechanism study","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.118546","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118546"}}