Published on April 15, 2019 in Cancer Cell volume 35(4).
PubMed ID: 30991027
FTO, an mRNA N(6)-methyladenosine (m(6)A) demethylase, was reported to promoteleukemogenesis. Using structure-based rational design, we have developed twopromising FTO inhibitors, namely FB23 and FB23-2, which directly bind to FTO andselectively inhibit FTO's m(6)A demethylase activity. Mimicking FTO depletion,FB23-2 dramatically suppresses proliferation and promotes thedifferentiation/apoptosis of human acute myeloid leukemia (AML) cell line cells andprimary blast AML cells in vitro. Moreover, FB23-2 significantly inhibits theprogression of human AML cell lines and primary cells in xeno-transplanted mice.Collectively, our data suggest that FTO is a druggable target and that targeting FTOby small-molecule inhibitors holds potential to treat AML.CI - Copyright © 2019 Elsevier Inc. All rights reserved.