{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:12:38Z","timestamp":1790745158897,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shandong Natural Science Fund","award":["ZR2023MH210"],"award-info":[{"award-number":["ZR2023MH210"]}]},{"name":"Shandong Natural Science Fund","award":["23-2-1-171-zyyd-jch"],"award-info":[{"award-number":["23-2-1-171-zyyd-jch"]}]},{"name":"Shandong Natural Science Fund","award":["82373785"],"award-info":[{"award-number":["82373785"]}]},{"name":"Qingdao Natural Science Fund","award":["ZR2023MH210"],"award-info":[{"award-number":["ZR2023MH210"]}]},{"name":"Qingdao Natural Science Fund","award":["23-2-1-171-zyyd-jch"],"award-info":[{"award-number":["23-2-1-171-zyyd-jch"]}]},{"name":"Qingdao Natural Science Fund","award":["82373785"],"award-info":[{"award-number":["82373785"]}]},{"name":"National Natural Science Fund","award":["ZR2023MH210"],"award-info":[{"award-number":["ZR2023MH210"]}]},{"name":"National Natural Science Fund","award":["23-2-1-171-zyyd-jch"],"award-info":[{"award-number":["23-2-1-171-zyyd-jch"]}]},{"name":"National Natural Science Fund","award":["82373785"],"award-info":[{"award-number":["82373785"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The internal tandem duplication mutation of FMS-like tyrosine kinase 3 (FLT3-ITD) is associated with high recurrence and mortality rates in acute myeloid leukemia (AML), making it a critical target for anti-AML therapies. Plinabulin is a diketopiperazines derivative that exhibits extensive anti-cancer potency by targeting \u03b2-tubulin. We designed and synthesized a novel FLT3 inhibitor, namely 5-3, based on the structure of plinabulin and evaluated its effect on FLT3-ITD mutant AML cells. The results indicated that 5-3 potently and selectively inhibits the growth of mutant FLT3-expressingleukemia cells, and had no effect on FLT3 wide-type cancer cells, suggesting the antiproliferative activity of 5-3 depends highly on FLT3-ITD expression. Mechanically, 5-3 significantly suppressed the phosphorylation of FLT3 signaling pathway, including STAT5, Erk and Akt. Moreover, the efficiency of compound 5-3 is not associated with Plinabulin\u2019s typical target, \u03b2-tubulin. In conclusion, the study identified diketopiperazine derivative as a novel FLT3-ITD selective inhibitor. These results demonstrated that 5-3 might be a drug candidate for the treatment of FLT3-ITD-positive AML.<\/jats:p>","DOI":"10.3390\/md23070289","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T08:24:17Z","timestamp":1752654257000},"page":"289","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Novel Diketopiperazine Derivative, Compound 5-3, Selectively Inhibited the Proliferation of FLT3-ITD Mutant Acute Myeloid Leukemia (AML) Cells"],"prefix":"10.3390","volume":"23","author":[{"given":"Shijie","family":"Bi","sequence":"first","affiliation":[{"name":"Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Rd, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yating","family":"Cao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Rd, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyuan","family":"Fang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Rd, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Chu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Rd, Qingdao 266003, China"},{"name":"Marine Biomedical Research Institute of Qiangdao, 23 Hongkong East Rd, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Rd, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Rd, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6625-2014","authenticated-orcid":false,"given":"Rilei","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Rd, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinbo","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Rd, Qingdao 266003, China"},{"name":"Marine Biomedical Research Institute of Qiangdao, 23 Hongkong East Rd, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Rd, Qingdao 266003, China"},{"name":"Marine Biomedical Research Institute of Qiangdao, 23 Hongkong East Rd, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiju","family":"Qiu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Rd, Qingdao 266003, China"},{"name":"Marine Biomedical Research Institute of Qiangdao, 23 Hongkong East Rd, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.3322\/caac.21873","article-title":"Acute myeloid leukemia management and research in 2025","volume":"75","author":"Kantarjian","year":"2025","journal-title":"CA A Cancer J. 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