FB23 is a potent and selective fat-mass and obesity-associated protein (FTO) inhibitor with an IC50 of 60 nM. FB23directly binds to FTO and selectively inhibits FTO's mRNA N6-methyladenosine (m6A) demethylase activity[1].
FB23 (72 hours) treatment inhibits acute myeloid leukemia (AML) cells proliferation with IC50 values of 44.8 μM, 23.6 μM for NB4 and MONOMAC6 AML cells[1].FB23 treatment causes the significant suppression of MYC targets, E2F targets, and G2M checkpoint signal cascades, which may contribute to the inhibitory effects of FTO inhibitors and FTO KD on cell cycle and proliferation. FB23 treatments activates apoptosis and p53 pathways[1].
A single dose of 3 mg/kg FB23 is i.p. administrated to Sprague Dawley (SD) rats for the pharmacokinetic profile. The Cmax and Tmax value of FB23 are 142.5 ng/mL and 0.4 hr, respectively[1].
[1]. Yue Huang, et al. Small-Molecule Targeting of Oncogenic FTO Demethylase in Acute Myeloid Leukemia. Cancer Cell. 2019 Apr 15;35(4):677-691.e10.