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Transl. Med."],"published-print":{"date-parts":[[2026,2,4]]},"abstract":"<jats:p>\n                    Dysregulation of RNA N\n                    <jats:sup>6<\/jats:sup>\n                    -methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) readers has been linked to various diseases, but the therapeutic potential of small-molecule inhibitors targeting them is of interest. Here, we reported the identification and characterization of a potent and selective first-in-class inhibitor (YL-5092) of YTHDC1, a nuclear RNA m\n                    <jats:sup>6<\/jats:sup>\n                    A reader. We provided a high-resolution cocrystal structure of the YTHDC1\u2013YL-5092 complex. In acute myeloid leukemia (AML) models, YL-5092 blocked the binding of YTHDC1 to its m\n                    <jats:sup>6<\/jats:sup>\n                    A substrates and reduced mRNA stability, resulting in apoptosis of AML cells and myeloid differentiation. In multiple xenograft models of AML representing disease heterogeneity, YL-5092 alone or in combination with standard AML therapy eliminated leukemia and extended survival. Moreover, YL-5092 functionally impaired leukemia stem cells yet spared normal hematopoietic counterparts. Collectively, our work demonstrates the efficacy of a selective YTHDC1 inhibitor and suggests that targeting of m\n                    <jats:sup>6<\/jats:sup>\n                    A readers is a potential strategy in the treatment of hematologic cancers.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adu3137","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T18:58:12Z","timestamp":1770231492000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Small-molecule inhibition of YTHDC1 as a strategy against acute myeloid leukemia in mouse models"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8142-3977","authenticated-orcid":true,"given":"Hailin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 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