Fat mass and obesity associated gene (fto) is significantly related to obesity, which was found in human patients and confirmed in rodent studies.FTO protein is a nucleic acid demethylase, targeting mainly N6-methyl-adenosine (N6-meA) in message RNA.It is very attractive target for anti-obesity drug discovery.However, up to now, none drug-like inhibitor targeting FTO protein was reported.Here, we identified a novel serial of drug-like small-molecule inhibitors using structure-based drug design method, and measured their inhibition activity in enzymatic assay and binding affinity using biophysics methods.The lead compound binds to FTO proteins substrate site and inhibits FTO enzymatic activity with IC50 about 22 μM.It is expected that these compounds will be useful to investigate the biological functions of FTO, besides their potential therapeutic applications.