| First Author | Huang Y | Year | 2019 |
| Journal | Cancer Cell | Volume | 35 |
| Issue | 4 | Pages | 677-691.e10 |
| PubMed ID | 30991027 | Mgi Jnum | J:274181 |
| Mgi Id | MGI:6294995 | Doi | 10.1016/j.ccell.2019.03.006 |
| Citation | Huang Y, et al. (2019) Small-Molecule Targeting of Oncogenic FTO Demethylase in Acute Myeloid Leukemia. Cancer Cell 35(4):677-691.e10 |
| abstractText | FTO, an mRNA N(6)-methyladenosine (m(6)A) 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 m(6)A 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 xeno-transplanted mice. Collectively, our data suggest that FTO is a druggable target and that targeting FTO by small-molecule inhibitors holds potential to treat AML. |
