{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:40:33Z","timestamp":1792449633673,"version":"4.5.0"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"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":["82360679"],"award-info":[{"award-number":["82360679"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017957","name":"Health Commission of Guizhou Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004001","name":"Guizhou Provincial Science and Technology Department","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018555","name":"Science and Technology Program of Guizhou Province","doi-asserted-by":"publisher","award":["QKHPTRC-CXTD[2022]012"],"award-info":[{"award-number":["QKHPTRC-CXTD[2022]012"]}],"id":[{"id":"10.13039\/501100018555","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018555","name":"Science and Technology Program of Guizhou Province","doi-asserted-by":"publisher","award":["2022]-293"],"award-info":[{"award-number":["2022]-293"]}],"id":[{"id":"10.13039\/501100018555","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.bioorg.2025.108912","type":"journal-article","created":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T22:21:48Z","timestamp":1755987708000},"page":"108912","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Machine learning-aided design, synthesis and biological evaluation of novel 4-(imidazo[1,2-a]pyridine-3\u2011carbonyl) phenyl urea derivatives as potent FLT3 inhibitors"],"prefix":"10.1016","volume":"164","author":[{"given":"Qiang","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lvjia","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangdong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxin","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoran","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianlu","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihuan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changkuo","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"2","key":"10.1016\/j.bioorg.2025.108912_bb0005","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1159\/000536152","article-title":"Pathophysiology of acute myeloid leukemia","volume":"147","author":"Wachter","year":"2024","journal-title":"Acta Haematol."},{"issue":"1","key":"10.1016\/j.bioorg.2025.108912_bb0010","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1097\/01.JAA.0000995680.52352.b5","article-title":"Acute myeloid leukemia: Current understanding and management","volume":"37","author":"Becker","year":"2024","journal-title":"JAAPA"},{"issue":"3","key":"10.1016\/j.bioorg.2025.108912_bb0015","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1002\/ajh.26822","article-title":"Acute myeloid leukemia: 2023 update on diagnosis, risk-stratification, and management","volume":"98","author":"Shimony","year":"2023","journal-title":"Am. J. Hematol."},{"issue":"2","key":"10.1016\/j.bioorg.2025.108912_bb0020","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1159\/000535500","article-title":"Geriatric assessment in acute myeloid leukemia","volume":"147","author":"Woods","year":"2024","journal-title":"Acta Haematol."},{"issue":"9","key":"10.1016\/j.bioorg.2025.108912_bb0025","doi-asserted-by":"crossref","first-page":"6245","DOI":"10.3390\/curroncol29090491","article-title":"Management of acute myeloid leukemia: a review for general practitioners in oncology","volume":"29","author":"Stubbins","year":"2022","journal-title":"Curr. Oncol. Rep."},{"key":"10.1016\/j.bioorg.2025.108912_bb0030","article-title":"Advances in acute myeloid leukemia","volume":"375","author":"Newell","year":"2021","journal-title":"BMJ"},{"issue":"1","key":"10.1016\/j.bioorg.2025.108912_bb0035","doi-asserted-by":"crossref","first-page":"16","DOI":"10.6004\/jnccn.2021.0002","article-title":"NCCN guidelines insights: acute myeloid leukemia","volume":"19","author":"Pollyea","year":"2021","journal-title":"J. Natl. Compr. Cancer Netw."},{"issue":"1","key":"10.1016\/j.bioorg.2025.108912_bb0040","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s00428-022-03430-4","article-title":"The international consensus classification of acute myeloid leukemia","volume":"482","author":"Weinberg","year":"2023","journal-title":"Virchows Arch."},{"issue":"2","key":"10.1016\/j.bioorg.2025.108912_bb0045","doi-asserted-by":"crossref","first-page":"308","DOI":"10.3324\/haematol.2022.280801","article-title":"The clinical impact of the molecular landscape of acute myeloid leukemia","volume":"108","author":"Kayser","year":"2023","journal-title":"Haematologica"},{"issue":"4","key":"10.1016\/j.bioorg.2025.108912_bb0050","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s11912-024-01503-y","article-title":"Novel therapeutic targets in acute myeloid leukemia (AML)","volume":"26","author":"Wysota","year":"2024","journal-title":"Curr. Oncol. Rep."},{"issue":"1","key":"10.1016\/j.bioorg.2025.108912_bb0055","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13045-023-01424-6","article-title":"Recent advances in targeted therapies in acute myeloid leukemia","volume":"16","author":"Bhansali","year":"2023","journal-title":"J. Hematol. Oncol."},{"issue":"2","key":"10.1016\/j.bioorg.2025.108912_bb0060","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":"8","key":"10.1016\/j.bioorg.2025.108912_bb0065","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.3390\/cancers15082312","article-title":"Targeting FLT3 mutation in acute myeloid leukemia: current strategies and future directions","volume":"15","author":"Fedorov","year":"2023","journal-title":"Cancers"},{"key":"10.1016\/j.bioorg.2025.108912_bb0070","doi-asserted-by":"crossref","DOI":"10.1016\/j.blre.2021.100905","article-title":"A review of FLT3 inhibitors in acute myeloid leukemia","volume":"52","author":"Zhao","year":"2022","journal-title":"Blood Rev."},{"issue":"6","key":"10.1016\/j.bioorg.2025.108912_bb0075","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1097\/CCO.0000000000001094","article-title":"Advances in the pathogenesis of FLT3 -mutated acute myeloid leukemia and targeted treatments","volume":"36","author":"Travaglini","year":"2024","journal-title":"Curr. Opin. Oncol."},{"issue":"10","key":"10.1016\/j.bioorg.2025.108912_bb0080","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.3390\/cancers16101819","article-title":"FLT3-mutated leukemic stem cells: mechanisms of resistance and new therapeutic targets","volume":"16","author":"Capelli","year":"2024","journal-title":"Cancers"},{"issue":"3","key":"10.1016\/j.bioorg.2025.108912_bb0085","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/s41375-019-0694-3","article-title":"FLT3 inhibitors in acute myeloid leukemia: ten frequently asked questions","volume":"34","author":"Antar","year":"2020","journal-title":"Leukemia"},{"issue":"6","key":"10.1016\/j.bioorg.2025.108912_bb0090","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1007\/s11864-024-01202-7","article-title":"Emerging DNA methylome targets in FLT3-ITD-Positive acute myeloid leukemia: combination therapy with clinically approved FLT3 inhibitors","volume":"25","author":"Tecik","year":"2024","journal-title":"Curr. Treat. Options in Oncol."},{"key":"10.1016\/j.bioorg.2025.108912_bb0095","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2021.107844","article-title":"Strategies targeting FLT3 beyond the kinase inhibitors","volume":"225","author":"Almatani","year":"2021","journal-title":"Pharmacol. Ther."},{"issue":"6","key":"10.1016\/j.bioorg.2025.108912_bb0100","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1021\/acs.jmedchem.0c01851","article-title":"FLT3 inhibitors in acute myeloid leukemia: challenges and recent developments in overcoming resistance","volume":"64","author":"Wang","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.108912_bb0105","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.ejmech.2019.06.002","article-title":"Dual FLT3 inhibitors: against the drug resistance of acute myeloid leukemia in recent decade","volume":"178","author":"Yuan","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.108912_bb0110","doi-asserted-by":"crossref","DOI":"10.1016\/j.leukres.2024.107505","article-title":"A systematic review of second-generation FLT3 inhibitors for treatment of patients with relapsed\/refractory acute myeloid leukemia","volume":"141","author":"Mohebbi","year":"2024","journal-title":"Leuk. Res."},{"issue":"1","key":"10.1016\/j.bioorg.2025.108912_bb0115","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":"11","key":"10.1016\/j.bioorg.2025.108912_bb0120","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.3390\/jcm12113647","article-title":"Gilteritinib: The story of a proceeding success into Hard-to-Treat FLT3-Mutated AML patients","volume":"12","author":"Molica","year":"2023","journal-title":"J. Clin. Med."},{"issue":"10","key":"10.1016\/j.bioorg.2025.108912_bb0125","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1182\/bloodadvances.2023010619","article-title":"A phase 1 study of the irreversible FLT3 inhibitor FF-10101 in relapsed or refractory acute myeloid leukemia","volume":"8","author":"Levis","year":"2024","journal-title":"Blood Adv."},{"issue":"23","key":"10.1016\/j.bioorg.2025.108912_bb0130","doi-asserted-by":"crossref","first-page":"6625","DOI":"10.1016\/j.bmc.2014.10.006","article-title":"Design, synthesis and biological evaluation of FLT3 covalent inhibitors with a resorcylic acid core","volume":"22","author":"Xu","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.108912_bb0135","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2022.116937","article-title":"Synthesis and biological evaluation of 4-(4-aminophenyl)-6-methylisoxazolo[3,4-b] pyridin-3-amine covalent inhibitors as potential agents for the treatment of acute myeloid leukemia","volume":"70","author":"Kang","year":"2022","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.108912_bb0140","article-title":"Design, synthesis, and biological evaluation of 4-(2-fluorophenoxy)pyridine derivatives as novel FLT3-ITD inhibitors","volume":"289","author":"Wu","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.108912_bb0145","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."},{"key":"10.1016\/j.bioorg.2025.108912_bb0150","doi-asserted-by":"crossref","first-page":"11894","DOI":"10.1021\/acs.jmedchem.5c00698","article-title":"Discovery of a Potent FLT3 Inhibitor (E)-4-(3-(3-Fluoro-4-(morpholinomethyl)styryl)-1H-indazol-6-yl)pyridin-2-amine for the Treatment of Acute Myeloid Leukemia with Multiple FLT3 Mutations","volume":"68","author":"Liu","year":"2025","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.108912_bb0155","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2025.117849","article-title":"Novel water-soluble and highly efficient dual type I\/II next generation inhibitors of FMS-like tyrosine kinase 3 (FLT3)","volume":"296","author":"Sellmer","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.108912_bb0160","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.bioorg.2025.108912_bb0165","doi-asserted-by":"crossref","first-page":"21752","DOI":"10.1021\/acs.jmedchem.4c00529","article-title":"Discovery of SILA-123 as a Highly Potent FLT3 Inhibitor for the Treatment of Acute Myeloid Leukemia with Various FLT3 Mutations","volume":"67","author":"Wei","year":"2024","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.108912_bb0170","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."},{"key":"10.1016\/j.bioorg.2025.108912_bb0175","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2023.106831","article-title":"Imidazopyridine-based kinase inhibitors as potential anticancer agents: A review","volume":"140","author":"Peytam","year":"2023","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.bioorg.2025.108912_bb0180","doi-asserted-by":"crossref","first-page":"4333","DOI":"10.1016\/j.bmc.2015.06.033","article-title":"Discovery of novel N-(5-(tert-butyl)isoxazol-3-yl)-N\u2032-phenylurea analogs as potent FLT3 inhibitors and evaluation of their activity against acute myeloid leukemia in vitro and in vivo","volume":"23","author":"Xu","year":"2015","journal-title":"Bioorg. Med. Chem."},{"issue":"1","key":"10.1016\/j.bioorg.2025.108912_bb0185","doi-asserted-by":"crossref","first-page":"286","DOI":"10.6023\/cjoc202403053","article-title":"Synthesis and anti-acute myeloid leukemia activity of cyclopropane-1,1-diamide derivatives containing imidazo[1,2-a]pyridine","volume":"45","author":"Wu","year":"2024","journal-title":"Chin. J. Org. Chem."},{"key":"10.1016\/j.bioorg.2025.108912_bb0190","doi-asserted-by":"crossref","DOI":"10.25259\/AJC_220_2024","article-title":"Integrating machine learning, docking analysis, molecular dynamics, and experimental validation for accelerated discovery of novel FLT3 inhibitors against AML","volume":"18","author":"Zhao","year":"2025","journal-title":"Arab. J. Chem."},{"key":"10.1016\/j.bioorg.2025.108912_bb0195","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2023.115066","article-title":"PLM-101 is a novel and potent FLT3\/RET inhibitor with less adverse effects in the treatment of acute myeloid leukemia","volume":"165","author":"Choi","year":"2023","journal-title":"Biomed. Pharmacother."},{"issue":"5","key":"10.1016\/j.bioorg.2025.108912_bb0200","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.3390\/cancers14051164","article-title":"Hui, Role of biomarkers in FLT3 AML","volume":"14","author":"Nitika","year":"2022","journal-title":"Cancers"},{"issue":"20","key":"10.1016\/j.bioorg.2025.108912_bb0205","doi-asserted-by":"crossref","first-page":"6429","DOI":"10.3390\/jcm12206429","article-title":"A review of FLT3 kinase inhibitors in AML","volume":"12","author":"Negotei","year":"2023","journal-title":"J. Clin. Med."},{"issue":"9","key":"10.1016\/j.bioorg.2025.108912_bb0210","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1111\/bcp.14022","article-title":"Effects of CYP3A inhibitors on the pharmacokinetics of quizartinib, a potent and selective FLT3 inhibitor, and its active metabolite","volume":"85","author":"Li","year":"2019","journal-title":"Br. J. Clin. Pharmacol."},{"issue":"14","key":"10.1016\/j.bioorg.2025.108912_bb0215","doi-asserted-by":"crossref","first-page":"2984","DOI":"10.1182\/blood-2009-05-222034","article-title":"AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML)","volume":"114","author":"Zarrinkar","year":"2009","journal-title":"Blood"}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206825007928?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206825007928?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T11:58:52Z","timestamp":1777463932000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0045206825007928"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":43,"alternative-id":["S0045206825007928"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2025.108912","relation":{"is-supplemented-by":[{"id-type":"uri","id":"https:\/\/github.com\/Yihuan-Zhao93\/FLT3ML","asserted-by":"subject"}]},"ISSN":["0045-2068"],"issn-type":[{"value":"0045-2068","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Machine learning-aided design, synthesis and biological evaluation of novel 4-(imidazo[1,2-a]pyridine-3\u2011carbonyl) phenyl urea derivatives as potent FLT3 inhibitors","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2025.108912","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"108912"}}