De novo Design and Synthesis of Pyrazoles as FTO Inhibitors

The fat-mass and obesity-associated (FTO) gene, located on human chromosome 16, contains the codes for the FTO protein, whose expression has been positively correlated to conditions such as obesity and cardiovascular disease. The FTO protein is a homolog of the AlkB family of proteins and has been shown to demethylate the 3-methyluracil in RNA. This purported mechanism of RNA demethylation has led to the association of the FTO protein with metabolic and fat-mass homeostasis. As the rate of obesity continues to climb in the modern world, the FTO Clark group hopes to inhibit the demethylation of RNA performed by the FTO gene.

Working in collaboration with the Brah group, which specializes in computational chemistry, the Clark group is designing novel pyrazole derivatives for FTO protein inhibition and plan to test their compounds’ efficacy through a variety of bioassays.