Small-molecule targeting of oncogenic FTO demethylase in acute myeloid leukemia
By Yue Huang, R. Su, Yue Sheng, Lei Dong, Ze Dong, Hongjiao Xu, Tengfeng Ni, Zijie Zhang, Tao Zhang, Chenying Li and 18 more. Cancer Cell, 2019
772 citations recorded by the source corpus.
Summary FTO, a mRNA N6-methyladenosine (m6A) demethylase, was reported to promote leukemogenesis. Using structure-based rational design, we have developed two promising FTO inhibitors, namely FB23 and FB23-2, which directly bind to FTO and selectively inhibit FTO’s m6A demethylase activity. Mimicking FTO depletion, FB23-2 dramatically suppresses proliferation and promotes the differentiation/apoptosis of human acute myeloid leukemia (AML) cell line cells and primary blast AML cells in vitro. Moreover, FB23-2 significantly inhibits the progression of human AML cell lines and primary cells in xenotransplanted mice. Collectively, our data suggest that FTO is a druggable target and that targeting FTO by small-molecule inhibitors holds potential to treat AML.
Subfields: Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/35e7fe58fecd406e11c3143c1841cc47a26776d0
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In Molecular Biology
Citations in the corpus
- The m6A reader YTHDF1 promotes ovarian cancer progression via augmenting EIF3C translation (2020, background): “FTO inhibitors suppress proliferation and induce apoptosis of human acute myeloid leukemia (AML) cells, thus exhibits a potential therapeutic for AML (13,33).”
- m6A RNA methylation: from mechanisms to therapeutic potential (2021, positive): “Additionally, m 6 A has been implicated in the pathogenesis of a variety of diseases, including in numerous cancer types and in type 2 diabetes (Batista, 2017; De Jesus et al , 2019; Ianniello et al , 2019; Yang et al , 2019b; Huang et al , 2020).”
- Functions of N6-methyladenosine and its role in cancer (2019, background): “As another inhibitor of FTO, FB23–2 impairs proliferation and enhances differentiation of AML cells [68].”