{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T15:28:25Z","timestamp":1793978905885,"version":"4.8.0"},"reference-count":34,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81903472"],"award-info":[{"award-number":["81903472"]}],"id":[{"id":"10.13039\/501100001809","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":[[2026,12]]},"DOI":"10.1016\/j.ejmech.2026.119289","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:27:17Z","timestamp":1788305237000},"page":"119289","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Discovery of a highly selective FLT3-ITD inhibitor with potent antileukemic activity based on 4-(2-fluorophenoxy)pyridine scaffold"],"prefix":"10.1016","volume":"319","author":[{"given":"Zhongyuan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingmei","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue'e","family":"Chai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4709-9989","authenticated-orcid":false,"given":"Weike","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.ejmech.2026.119289_bib1","first-page":"12","article-title":"Cancer statistics","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. Clin."},{"issue":"1","key":"10.1016\/j.ejmech.2026.119289_bib2","doi-asserted-by":"crossref","DOI":"10.1080\/07853890.2025.2557507","article-title":"Global, regional and national epidemiology of acute myeloid leukemia (1990\u20132021): a statistical analysis of incidence, mortality, and DALYs","volume":"57","author":"Wu","year":"2025","journal-title":"Ann. Med."},{"key":"10.1016\/j.ejmech.2026.119289_bib3","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41408-021-00425-3","article-title":"Acute myeloid leukemia: current progress and future directions","volume":"11","author":"Kantarjian","year":"2021","journal-title":"Blood Cancer J."},{"issue":"Suppl. 1","key":"10.1016\/j.ejmech.2026.119289_bib4","doi-asserted-by":"crossref","first-page":"4124","DOI":"10.1182\/blood-2021-146251","article-title":"A temporal and multinational assessment of acute myeloid leukemia (AML) cancer incidence, survival, and disease burden","volume":"138","author":"Anderson","year":"2021","journal-title":"Blood"},{"issue":"5","key":"10.1016\/j.ejmech.2026.119289_bib5","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1002\/ajh.27625","article-title":"Acute myeloid leukemia: 2025 update on diagnosis, risk-stratification, and management","volume":"100","author":"Shimony","year":"2025","journal-title":"Am. J. Hematol."},{"issue":"5","key":"10.1016\/j.ejmech.2026.119289_bib6","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1182\/blood-2002-02-0492","article-title":"The roles of FLT3 in hematopoiesis and leukemia","volume":"100","author":"Gilliland","year":"2002","journal-title":"Blood"},{"issue":"3","key":"10.1016\/j.ejmech.2026.119289_bib7","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1152\/physrev.00029.2018","article-title":"FMS-like tyrosine kinase 3\/FLT3: from basic science to clinical implications","volume":"99","author":"Kazi","year":"2019","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.ejmech.2026.119289_bib8","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.pharmthera.2018.06.016","article-title":"Structural and clinical consequences of activation loop mutations in class III receptor tyrosine kinases","volume":"191","author":"Klug","year":"2018","journal-title":"Pharmacol. Ther."},{"issue":"2","key":"10.1016\/j.ejmech.2026.119289_bib9","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1111\/cas.14274","article-title":"FLT3 mutations acute myeloid leukemia: therapeutic paradigm beyond inhibitor development","volume":"111","author":"Kiyoi","year":"2020","journal-title":"Cancer Sci."},{"issue":"2","key":"10.1016\/j.ejmech.2026.119289_bib10","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41375-018-0357-9","article-title":"Targeting FLT3 mutations in AML: review of current knowledge and evidence","volume":"33","author":"Daver","year":"2019","journal-title":"Leukemia"},{"issue":"5","key":"10.1016\/j.ejmech.2026.119289_bib11","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/sj.onc.1203354","article-title":"Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines","volume":"19","author":"Hayakawa","year":"2000","journal-title":"Oncogene"},{"issue":"12","key":"10.1016\/j.ejmech.2026.119289_bib12","doi-asserted-by":"crossref","first-page":"3907","DOI":"10.1182\/blood.V96.12.3907","article-title":"Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways","volume":"96","author":"Mizuki","year":"2000","journal-title":"Blood"},{"issue":"6","key":"10.1016\/j.ejmech.2026.119289_bib13","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s00412-014-0482-9","article-title":"DNA damage accumulation and repair defects in acute myeloid leukemia: implications for pathogenesis, disease progression, and chemotherapy resistance","volume":"123","author":"Esposito","year":"2014","journal-title":"Chromosoma"},{"issue":"11","key":"10.1016\/j.ejmech.2026.119289_bib14","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.3390\/cells9112493","article-title":"Molecular mechanisms of resistance to FLT3 inhibitors in acute myeloid leukemia: ongoing challenges and future treatments","volume":"9","author":"Scholl","year":"2020","journal-title":"Cells"},{"issue":"21","key":"10.1016\/j.ejmech.2026.119289_bib15","doi-asserted-by":"crossref","first-page":"12403","DOI":"10.1021\/acs.jmedchem.0c00696","article-title":"Small-Molecule fms-like tyrosine kinase 3 inhibitors: an attractive and efficient method for the treatment of Acute Myeloid leukemia","volume":"63","author":"Zhong","year":"2020","journal-title":"J. Med. Chem."},{"issue":"26","key":"10.1016\/j.ejmech.2026.119289_bib16","doi-asserted-by":"crossref","first-page":"3403","DOI":"10.1182\/blood-2017-05-782292","article-title":"Midostaurin approved for FLT3-mutated AML","volume":"129","author":"Levis","year":"2017","journal-title":"Blood"},{"issue":"10","key":"10.1016\/j.ejmech.2026.119289_bib17","article-title":"The combination therapy with sorafenib in therapeutic strategy of acute myeloid leukemia. Is it promising? A narrative review","volume":"8","author":"Nakhaei Shamahmood","year":"2025","journal-title":"Health Sci. Rep."},{"issue":"5","key":"10.1016\/j.ejmech.2026.119289_bib18","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1111\/bjh.13353","article-title":"A phase I\/II study of sunitinib and intensive chemotherapy in patients over 60 years of age with acute myeloid leukaemia and activating FLT3 mutations","volume":"169","author":"Fiedler","year":"2015","journal-title":"Br. J. Haematol."},{"issue":"11","key":"10.1016\/j.ejmech.2026.119289_bib19","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1182\/blood.V108.11.158.158","article-title":"Phase 1\/2 study of tandutinib (MLN518) plus standard induction chemotherapy in newly diagnosed acute myelogenous leukemia (AML)","volume":"108","author":"DeAngelo","year":"2006","journal-title":"Blood"},{"issue":"1","key":"10.1016\/j.ejmech.2026.119289_bib20","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s13045-024-01617-7","article-title":"Quizartinib: a potent and selective FLT3 inhibitor for the treatment of patients with FLT3-ITD-positive AML","volume":"17","author":"Cortes","year":"2024","journal-title":"J. Hematol. Oncol."},{"issue":"15","key":"10.1016\/j.ejmech.2026.119289_bib21","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1200\/JCO.23.01061","article-title":"Crenolanib and intensive chemotherapy in adults with newly diagnosed FLT3-mutated AML","volume":"42","author":"Wang","year":"2024","journal-title":"J. Clin. Oncol."},{"issue":"4","key":"10.1016\/j.ejmech.2026.119289_bib22","doi-asserted-by":"crossref","first-page":"265.e1","DOI":"10.1016\/j.jtct.2022.12.006","article-title":"Outcomes in patients with FLT3-mutated relapsed\/refractory acute myelogenous leukemia who underwent transplantation in the phase 3 ADMIRAL trial of gilteritinib versus salvage chemotherapy","volume":"29","author":"Perl","year":"2023","journal-title":"Transplant. Cell. Ther"},{"issue":"4","key":"10.1016\/j.ejmech.2026.119289_bib23","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1158\/2159-8290.CD-19-1011","article-title":"Advances in the treatment of acute myeloid leukemia: new drugs and new challenges","volume":"10","author":"Short","year":"2020","journal-title":"Cancer Discov."},{"key":"10.1016\/j.ejmech.2026.119289_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2024.117788","article-title":"Targeting FMS-like tyrosine kinase 3 (FLT3) in acute myeloid leukemia: novel molecular approaches and therapeutic challenges","volume":"182","author":"Rataj","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.ejmech.2026.119289_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2024.116962","article-title":"Identification of furo[2,3-d]pyrimidin-4-ylsulfanyl-1,3,4-thiadiazole derivatives as novel FLT3-ITD inhibitors","volume":"280","author":"Moradi","year":"2024","journal-title":"Eur. J. Med. Chem."},{"issue":"8","key":"10.1016\/j.ejmech.2026.119289_bib26","doi-asserted-by":"crossref","first-page":"7955","DOI":"10.1021\/acs.jmedchem.4c03023","article-title":"Discovery of FLT3-ITD inhibitor clifutinib: a novel biphenylacetylene urea derivative in clinical trials for the treatment of Relapsed\/Refractory FLT3-ITD+ acute Myeloid leukemia","volume":"68","author":"Liu","year":"2025","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.119289_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2022.114292","article-title":"Synthesis of 2H-Imidazo[2\u2032,1\u2032:2,3][1,3]thiazolo[4,5-e]isoindol-8-yl-phenylureas with promising therapeutic features for the treatment of acute myeloid leukemia (AML) with FLT3\/ITD mutations","volume":"235","author":"Cilibrasi","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.119289_bib28","article-title":"Design, synthesis and biological evaluation of 8-phenylquinazolin-2-amine derivatives as FLT3 covalent inhibitors targeting cysteine 828 in the ATP pocket","volume":"301","author":"Wei","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.119289_bib29","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2025.117492","article-title":"Design, synthesis, and biological evaluation of pyridine-based derivatives as FLT3 inhibitors for the treatment of acute myeloid leukemia","volume":"289","author":"Wu","year":"2025","journal-title":"Eur. J. Med. Chem."},{"issue":"15","key":"10.1016\/j.ejmech.2026.119289_bib30","doi-asserted-by":"crossref","first-page":"4410","DOI":"10.1016\/j.bmc.2015.06.026","article-title":"Design and biological evaluation of novel 4-(2-fluorophenoxy)quinoline derivatives bearing an imidazolone moiety as c-Met kinase inhibitors","volume":"23","author":"Liao","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.119289_bib31","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1158\/2159-8290.CD-15-0060","article-title":"Characterizing and overriding the structural mechanism of the quizartinib-resistant FLT3 \"gatekeeper\" F691L mutation with PLX3397","volume":"5","author":"Smith","year":"2015","journal-title":"Cancer Discov."},{"key":"10.1016\/j.ejmech.2026.119289_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2025.109229","article-title":"Identification of 2,4-disubstitued pyridine derivatives as potent FMS-like tyrosine receptor kinase 3 (FLT3) inhibitors","volume":"167","author":"Wang","year":"2025","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2026.119289_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2020.112309","article-title":"Design, synthesis and biological activity of novel 2,3,4,5-tetra-substituted thiophene derivatives as PI3K\u03b1 inhibitors with potent antitumor activity","volume":"197","author":"Liao","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.119289_bib34","article-title":"Discovery of pyridine-based derivatives as FLT3 inhibitors for the treatment of acute myeloid leukemia","volume":"283","author":"Chen","year":"2025","journal-title":"Eur. J. Med. Chem."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523426007348?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523426007348?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T15:06:26Z","timestamp":1793977586000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523426007348"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,12]]},"references-count":34,"alternative-id":["S0223523426007348"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.119289","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery of a highly selective FLT3-ITD inhibitor with potent antileukemic activity based on 4-(2-fluorophenoxy)pyridine scaffold","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.119289","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 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":"119289"}}